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Building a Future Free of Age-Related Disease

Kurzgesagt – It Is Time to Talk About Curing Aging

The level of interest and support for rejuvenation biotechnology that targets age-related diseases is growing. Over the last few years, we have seen a significant increase in the number of popular science articles, news stories and research papers focusing on the idea that the aging processes are something we can target with therapies to prevent or cure age-related diseases.

With human clinical trials launched this year for senolytic therapies that remove toxic, aged senescent cells from the body, that interest level is only growing. Later this year, there are also going to be human trials for DNA repair, which has great potential for cancer and aging therapies. It is no longer a case of “can it be done” but “when will it be done” when it comes to bringing aging under medical control.

Bringing aging under medical control

You may remember the excellent video about aging that Kurzgesagt recently published on Youtube, where they explored what aging is and if science should do something about it in order to promote healthy longevity. We were pleased to have worked with Kurzgesagt to help create that video, and today, we are equally pleased to announce that a second video has been made in collaboration with them.

The video today takes a look at some of the most promising approaches that science is taking to address the aging processes. It covers removing senescent cells to improve tissue repair, increasing NAD in cells to increase DNA repair and improve cell function, and finally the amazing progress being made with stem cell therapies to combat diseases.

LEAF president Keith Comito, Vice President Oliver Medvedik, and other members of the team helped Kurzgesagt in the making of this video. We believe that bringing this topic to public attention now is very important indeed, especially if we take into account rapid population aging and the forecast that people aged 60+ will make about 1/3 of the global population by 2100.

The video today and the previous video by Kurzgesagt tie into our grand strategy. Last year at the DNA Conference in the Netherlands we were talking about engaging the wider public audience via popular YouTube channels and personalities and now we have begun to deliver on that promise.

Conclusion

Science is progressing in this area very rapidly, so it is important that we have these discussions now, before rejuvenation therapies arrive, so that we can promote equal access to these innovative medicines. Popular broadcasters such as Kurzgesagt are absolutely vital in helping to encourage public dialogue about the topic of aging. We would like to thank Kurzgesagt for this opportunity to work with them again, and we look forward to future collaborations.

 

Rejuvenation Roundup October 2017

Today, we launch a new series on LEAF: the monthly roundup where we briefly discuss the latest news and articles about aging and rejuvenation from a number of different sources. We hope these roundups will be a great way to keep our readers in the loop.

Without further ado, let’s have a look at the highlights of the last month.

SENS Research Foundation and Spiegel Lab team up against glucosepane

This piece of news is a just a little bit older than one month, but I find it’s important enough to have a look at anyway. Cellular crosslinks are one of the factors driving human aging; they’re unwanted, accidental links between otherwise independently moving proteins, caused by the reaction of blood sugar and other molecules with the proteins themselves.

This binding causes the stiffening of the tissues of which crosslinked proteins are a part, which is really bad news, as this causes systolic blood pressure to rise and increases the risk of strokes with age, among other less-than-desirable ailments.

One of the most common crosslinks is glucosepane, a rather complex molecule that can be isolated only in very small amounts from the human body (and not even in a pure form). This limitation has made it hard for researchers to find ways to break glucosepane crosslinks because there was no easy way to test potential crosslink breaking molecules.

However, the Spiegel lab has managed to fully synthesize glucosepane and is using some of its derivatives in an attempt to create monoclonal antibodies that can seek and destroy glucosepane in the body. We’re looking forward to hearing more about it!

The arsenal against cellular senescence

Cellular senescence is a well-known hallmark of aging; while moderate amounts of senescent cells have a positive role in the body, their life-long accumulation eventually contributes to a number of age-related pathologies. Thankfully, senolytic drugs to selectively eliminate excess senescent cells are all the rage lately, and as Fight Aging! discusses in this article, several clearance methods are currently in development, while many others are to be expected, as initial successes for pioneers in this field will encourage further efforts from others. It’s certainly good to know that we might be spoiled for choice!

Dr. James Kirkland confirmed as a speaker at Undoing Aging 2018

As you might already know, Undoing Aging 2018, a conference on rejuvenation biotechnologies organized by Forever Healthy Foundation and SENS Research Foundation, will take place in March 2018 in Berlin, Germany. Early in October this year, Dr. James Kirkland has been confirmed as a speaker.

Dr. Kirkland is the director of the Kogod Center on Aging at Mayo Clinic, and he was the first researcher to publish a paper on senolytics. It goes without saying that he’ll be discussing cellular senescence, among a number of other interesting topics. LEAF representatives are also going to attend the conference and will hopefully get back with a set of interviews with the renowned researchers of aging!

Machine learning in tumor recognition

Machine learning is an important tool in research these days, as it allows researchers to quickly carry out extensive data analyses that would take months for humans. An exciting application of this technology, discussed in a previous article, is tumor recognition in magnetic resonance imagery of patients’ brains.

Professor George Biros of the ICES Parallel Algorithms for Data Analysis and Simulation Group recently presented the results of a decade’s worth of work on a machine learning system that can identify gliomas with impressive accuracy in a much shorter time it would take for human professionals.

Early and accurate detection of tumors, especially aggressive ones such as gliomas, is crucial for successful therapeutic interventions, and this kind of technology might well pave the way to a future where most, if not all, cancers can be busted before they have a chance to wreak havoc.

The Hallmarks of aging

Telomeres are probably the first things that pop into people’s heads when thinking about aging. The fact that telomeres shorten with age is well-known, while the existence of the enzyme telomerase and its role in replenishing telomeres is possibly a bit less known by the general public. If you’d like to learn a bit more about this particular hallmark of aging, it might be worth taking a look at this concise but clear article on Geroscience.

Since we are on the topic of hallmarks, let’s have a look at Steve Hill’s summary of the genomic instability hallmark. In a nutshell, this is essentially an accumulation of DNA damage that can occur in several ways—exposure to radiation or chemicals, for example, or even during normal cell replication. The results of genomic instability are many and not too pleasant; it can lead to cell dysfunction, cellular senescence, or even cancer. Thus, to fully address age-related diseases, we will need means of DNA repair that solve this problem, and while we’re not there yet, some potential solutions are in the works.

FA! announces the 2017 winter fundraiser for SENS

There are two downsides to scientific research: it isn’t super cheap, and it won’t carry itself out. This is why ensuring sufficient funding is crucial to the development of rejuvenation biotechnologies, and crowdfunding initiatives are a big part of this. Like every year for a while now, FightAging! is running a winter matching fund for SENS Research Foundation.

Together with other generous folks, FA! has put together a $36,000 fund to match SENS patrons’ donations for the next year in an attempt to help SENS reach the goal of $250,000 to finance several ongoing research projects at the Buck Institute and other laboratories. This is good news if you’re a SENS patron because your donations will be matched; if you aren’t, I guess this is a moment as good as any to consider becoming one!

Life Extension discussed by popular YouTubers

Life extension and rejuvenation biotechnologies need the support of a large community to really take off; a first, important step to reaching a wider public has been taken in the second half of October this year, when some of the big guns of advocacy have been fired for the first time: popular YouTube channels Kurzgesagt, CGP Grey, and Thunk have all published videos discussing and advocating for the possibility of putting an end to aging.

Combined, these three channels have over 8 million subscribers, and chances are good that other famous channels will follow suit and publish their own videos on the topic, reaching an even wider audience. In particular, I’m pleased to say that the Kurzgesagt’s video was created with the help of LEAF president Keith Comito, and I’m sure I speak for everyone here at LEAF when I say that we are all looking forward to further collaborations with Kurzgesagt!

Conference “Motivation to life extension” and other events in Moscow

On October 14 LEAF Director Elena Milova gave a talk at the conference  “Motivation for life extension” co-hosted by the Foundation Science for Life Extension and Singularity University Moscow Chapter. Elena shared with the audience her views regarding the evidence-based approaches to increase adherence to healthy lifestyle and high compliance. One of the best systems to effectively change one’s behavior to a more longevity-friendly is described in the book Influencer: The New Science of Leading Change that Elena is recommending you to read.

Later in October, the same partnership organized a lecture of the famous biohacker Serge Faguet, and Elena managed to get back with an interview with Serge.

MouseAge is funded!

Finally, we are delighted to announce that the MouseAge project at Lifespan.io reached its initial fundraising goal, and is now moving forward to the stretch goal.

Thanks to the devotion of the team, the work on the creating the application has already begun. Soon, a beta version of the application will be made available to backers via the Apple Store, allowing them to start using it in the lab and contributing to scientific progress.

We would like to thank everyone in the community who has supported the project and a special thank-you to investment mogul Jim Mellon and Bill Gelpi from Rocket games for their donations.

Coming up in November

The Lifespan Extension Advocacy Foundation, in collaboration with the Moscow Chapter of Singularity University, and consulting group Deloitte, is hosting an expert discussion in Moscow on how to inform the public about the potential of rejuvenation biotechnology. These experts believe that by raising awareness of new medical technologies to prevent aging, it could help to increase support for defeating age-related diseases and increasing the healthy period of life.

The panel discussion “6 ways to talk to people about ending aging” will bring together famous futurists, scientists, science popularizers and public figures who foster the dissemination of the idea to prevent aging in Russia and other countries, such as Jose Cordeiro (director of Humanity Plus), Valerija Udalova (director of Russian cryonics company KrioRus), Eugeny Kuznetsov (ambassador of Singularity University in Russia) and others.

Elena Milova will be moderating this discussion together with Jin Kolesnikov, co-founder of Singularity University Moscow Chapter. If you happen to be in Moscow on November 4, you are welcome to attend this event – please don’t forget to register and bring an ID with you.

Journal Club October Video Available

We have been talking about a number of new studies in past Journal Clubs, so we thought it was time to get into some aging theory. We chose to cover one of the most cited and highly regarded damage theories of aging in this edition of the club.

In this edition of Journal Club, we continued discussing the Hallmarks of Aging, one of the most popular aging theories and based on a damage repair based approach to the damage aging causes.

López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194-1217.

Thanks to our guests Dr. Laura Weston, biologist Sven Bulterijs and Lifespan Heros Joel Peterson and Bill Gelpi for joining us for the show.

Serge Faguet – Interview with a Biohacker

Serge Faguet is a Russian entrepreneur, the owner of a profitable travel company, Ostrovok, and the founder of several tech startups, including a new secret, AI-related one in Silicon Valley. For the last few weeks, his name has been all over the internet because of the article “I’m 32 and spent $200k on biohacking. Became calmer, thinner, extroverted, healthier & happier.

While his goals are without a doubt desirable (who would not want to be healthier and happier?), some of the public, including medical specialists, have received his story with some skepticism. On the other hand, those who support the idea of healthy longevity believe that Serge is a role model whose example should be taken seriously by each and every person.

LEAF Director Elena Milova attended a conference in Moscow, where Serge had been invited to talk about his system in more detail. After the event that was jointly organized by Mikhail Batin, the lead of Foundation Science for Life Extension and Open Longevity ICO, and Jin Kolesnikov, the co-founder of Singularity University Moscow Chapter, Elena had an opportunity to talk to Serge face to face. Today, we share with you his interview and commentary regarding his approach to health management.

Before our quick overview of Serge’s system, we would like to remind you of his principles for creating his approach to health and longevity. Here is the list from Hackernoon, where his article was published:

“In all these areas I use roughly the following framework to decide regarding specific tactics:

  • Is it scientifically sound? (i.e. are there studies if such are feasible?)
  • Is it logically sound? (i.e. is there a sound explanation behind the tactic?)
  • Is the estimated cost (risk, money, time/energy) worth the estimated benefit?
  • Do independent smart experts (e.g. doctors) agree with the approach?
  • Do they actually practice the approach themselves and with their families?
  • Do I track my objective/subjective metrics related to the tactic, if feasible?”

Relying on these principles, Serge has created his own personalized health and longevity strategy, which focuses on six key areas he has identified as important.

Sleep Hygiene

Serge believes that getting plenty of restorative deep and REM sleep on a regular basis is a key component in maintaining good health. Sleep is essential for the human body to repair and recover from injury, and there is plenty of evidence to suggest that a constant lack of sufficient sleep can lead to devastating consequences to health.

He monitors his sleep quality using the ŌURA health wearable device, although there are many others on the market to consider. Recording your health data and monitoring it over time is essential in properly managing your personal health and ensuring that the steps you are taking are effective.

Take steps to eliminate blue light sources three to four hours before sleep, as this wavelength of light is known to interfere with sleep. Studies have demonstrated that exposure to blue light can increase alertness[1-4] and can also stimulate cognitive functions[5-7]. Also, a recent study reported that exposure to blue light-emitting e-readers at bedtime may negatively affect sleep and the circadian system[8].

If you must use an e-reader or cell phone before sleeping, you may wish to consider a blue light filter, and some of them are available for free, though it must be said that, currently, the scientific evidence supporting them is just not there yet. However, you may wish to see if it works and improves your sleep, which is all the more reason why you should be monitoring your sleep quality and other biomarkers.

Another simple measure you can take is to reduce light pollution using heavy curtains that block light from outside or, failing that, a sleep mask to achieve the same outcome. If you have other light sources in your bedroom, such as LED clocks, cable TV boxes and other electronics with lights on them, cover the lights or remove them from the room completely.

Serge suggests to keep the room cool and humid between 18-19 Celsius, as being too warm can make sleeping difficult or reduce sleep quality.

Optimal Nutrition

Serge aims to eat a diet that keeps insulin levels stable, increases glucose disposal and optimizes growth factors, such as IGF-1 and mTOR, towards positive things like muscle growth and tissue repair and away from inflammation and cancer. He also avoids refined sugars, bread, pasta, fruit juice, candy, chocolate and other foods that have a high glycemic index and can cause insulin levels to spike.

He eats a mainly plant-based diet, and when buying animal products, he only buys organic, as cheaper food is frequently of lower quality and may have had harmful shortcuts taken to reduce the cost. From a nutritional perspective, it would probably be better to eat a small quantity of expensive, high-quality meat than a large quantity of cheap, low-quality meat.

Serge also avoids salt, as it raises blood pressure, and alcohol, which he believes can disrupt sleep.

Optimal Exercise

For his approach to fitness, Serge seeks to maximize metabolic benefits, such as hormones and insulin sensitivity, minimize the time spent exercising, and reduce the risk of injury.

To make the most of his time, he engages in high-intensity interval training (HIIT), a form of interval training that alternates short periods of high-intensity anaerobic exercise with lower-intensity recovery periods. In HIIT, one repeatedly alternates between a short burst of high-intensity exercise and a brief period of low-intensity activity until too exhausted to continue. Typically, HIIT sessions tend to last 30 minutes or less, though that time varies by fitness level.

Serge is also mindful to avoid long periods of sedentary activity, and sitting for long periods is well known to be harmful to health. Using standing desks or taking frequent breaks to walk around and stretch reduces the impact of sitting too much.

Mental Health

Serge believes that mental health is a key component of health and longevity, so he aims to maximize stress resilience, increase social support and foster a sense of purpose while avoiding negative emotional states.

In order to achieve this, he uses a combination of meditation and psychotherapy while avoiding lying and falling into other negative habits. Mental health is very important to well-being, and it is not something that should be neglected. There is some scientific data that suggests a small but positive effect of meditation on the length of telomeres[9].

Another set of data indicates that meditation may help to regulate the activity of certain brain cells that help to clear waste, which is possibly a way to postpone Alzheimer’s and other cognitive pathologies with age[10].

Medical Testing

When practicing a personal health and longevity strategy, everything you do could be meaningless. If you are not recording your health data, monitoring biomarkers and adjusting your approach based on this data, then what you are doing is faith-based medicine, not science. Taking drugs and supplements without keeping close watch on how they are affecting your body is not the way to optimize your health.

Serge uses many metrics to evaluate his approach, including DNA tests, blood tests, and sleep monitoring. He has a huge list of biomarkers he considers important and goes into detail here. Even if you cannot do hundreds, there are plenty of easy and cost-effective metrics you can and should be using to monitor your health.

Once you have an accurate picture of your health, you can then optimize and change your approach to see what works best for you. Methodical and scientific evaluation is the key to developing your health and longevity strategy.

Supplements and Drugs

Serge aims to improve his health and cognitive function through the use of drugs and supplements that have at least some level of scientific support.

He takes metformin, a diabetes drug that lowers blood sugar without causing hypoglycemia. Some data suggest that it may be beneficial in preventing cancer and heart disease, though, at this time, this is still unclear and more studies are needed. Other things, such as vitamin D, vitamin K2, group B vitamins, quercetin, magnesium, and melatonin, seem to have potential health benefits when applied in amounts prescribed by a medical advisor.

He takes a variety of supplements and hormones as part of his approach, although he is keen to stress the need for performing research before the start of a regimen.

Elena Milova’s commentary

During the lecture, I asked Serge if he had spent most of his money on treatment, diagnostics or something else. He said that the lion’s share went to analysts and medical advisors, whose job it was to consider each and every drug, supplement, therapy, and lifestyle measure that he was intended to implement.

Serge literally hired the best possible scientists in each relevant field to help him find out what would work well and what would be safe in his particular case. Yet, when making the final decision on whether he should take each measure or not, he studied the accumulated materials himself. Looking at how easily he can name biomarkers, symptoms and specific genes related to metabolic regulation, I believe that he learned quite a lot during this journey.

I find this fascinating. This amount of responsibility for one’s health is so rare! How did Serge manage to remain motivated to learn for a long period of time and acquire such self-discipline? He said that people should be passionate about what they do. Genuine passion will keep you inspired and keen to overcome obstacles until you reach the goal. If this is the influence of an entrepreneur’s mindset, I ask myself if we all should adopt it in order to become such daring managers of our own health and longevity.

Literature

[1] Lockley, S. W., & Gooley, J. J. (2006). Circadian photoreception: spotlight on the brain. Current Biology, 16(18), R795-R797. [2] Viola, A. U., James, L. M., Schlangen, L. J., & Dijk, D. J. (2008). Blue-enriched white light in the workplace improves self-reported alertness, performance and sleep quality. Scandinavian journal of work, environment & health, 297-306. [3] Rahman, S. A., Flynn-Evans, E. E., Aeschbach, D., Brainard, G. C., Czeisler, C. A., & Lockley, S. W. (2014). Diurnal spectral sensitivity of the acute alerting effects of light. Sleep, 37(2), 271-281. [4] Najjar, R. P., Wolf, L., Taillard, J., Schlangen, L. J., Salam, A., Cajochen, C., & Gronfier, C. (2014). Chronic artificial blue-enriched white light is an effective countermeasure to delayed circadian phase and neurobehavioral decrements. PloS one, 9(7), e102827. [5] Vandewalle, G., Gais, S., Schabus, M., Balteau, E., Carrier, J., Darsaud, A., … & Maquet, P. (2007). Wavelength-dependent modulation of brain responses to a working memory task by daytime light exposure. Cerebral cortex, 17(12), 2788-2795. [6] Vandewalle, G., Schmidt, C., Albouy, G., Sterpenich, V., Darsaud, A., Rauchs, G., … & Maquet, P. (2007). Brain responses to violet, blue, and green monochromatic light exposures in humans: prominent role of blue light and the brainstem. PloS one, 2(11), e1247. [7] Daneault, V., Hébert, M., Albouy, G., Doyon, J., Dumont, M., Carrier, J., & Vandewalle, G. (2014). Aging reduces the stimulating effect of blue light on cognitive brain functions. Sleep, 37(1), 85-96. [8] Chang, A. M., Aeschbach, D., Duffy, J. F., & Czeisler, C. A. (2015). Evening use of light-emitting eReaders negatively affects sleep, circadian timing, and next-morning alertness. Proceedings of the National Academy of Sciences, 112(4), 1232-1237. [9] Thimmapuram, J., Pargament, R., Sibliss, K., Grim, R., Risques, R., & Toorens, E. (2017). Effect of heartfulness meditation on burnout, emotional wellness, and telomere length in health care professionals. Journal of Community Hospital Internal Medicine Perspectives, 7(1), 21-27. [10] Wells, R. E., Yeh, G. Y., Kerr, C. E., Wolkin, J., Davis, R. B., Tan, Y., … & Press, D. (2013). Meditation’s impact on default mode network and hippocampus in mild cognitive impairment: a pilot study. Neuroscience letters, 556, 15-19.  

Neutrophils are a Key Player in Nerve Regeneration

The potential of the immune system to help repair tissue, including for peripheral nerve damage, Atherosclerosis, and Parkinson’s is considerable. Immune cells not only fight infection; as this new study shows, they also help the nervous system remove debris, paving the way for nerve regeneration following injury.

While previous studies suggested that nerve cell damage repair was conducted by other immune cell types, such as macrophages, researchers from Case Western Reserve University School of Medicine have shown that neutrophils also play a role.

What are Neutrophils?

Neutrophils are white blood cells created in the bone marrow, and they are normally the first responders to attack and injury. At the first sign of microbial invasion, they head to the site of injury as quickly as possible so that they can destroy the invaders. This is good, as it means that the body can mount a rapid defense the moment there is an infection, helping us to fight off illness and injury.

A new role for neutrophils

In the new study led by Dr. Richard Zigmond, the team discovered that damaged nerve cells produce a signals to summon neutrophils to the injury site in mice. Damaged sciatic nerves in the mice produced two signals to call in the neutrophils, Cxcl1 and Cxcl2; the levels of these signals were hundreds of times above what is normally produced in healthy cells.

Once the neutrophils arrive at the injury site, they engulf the cell debris that resulted from nerve damage, and they leave the area clean so that the cell can repair itself. The process is critical, as cells cannot repair properly if the injury site is not clear, and without neutrophils, nerves will not regenerate properly after being damaged.

Previous studies have suggested that macrophages are the most important immune cell for engulfing cell debris and clearing up the injury site around damaged nerves. The team had been studying injuries in engineered mice that lack a receptor on the surface of macrophages – CCR2 – which helps macrophages locate injury sites. They expected that in these mice, cell debris clearance following nerve injury would be dramatically reduced, but they were surprised to find it was unchanged. This was a real mystery that the team set out to solve.

They drew up a list of other types of cells that might be compensating for the loss of the macrophages and launched multiple tests to see which cells were picking up the slack. They created experiments to test this, including sorting immune cells found at injury sites by the molecules on their surfaces. They discovered that several different immune cells compensate for the lack of macrophages, so there is clearly considerable redundancy built into the system. The team also determined that the greatest contributor of these various cells to the removal of debris were neutrophils.

The researchers also found that if they depleted neutrophils, the level of nerve clearance was significantly reduced in both normal mice and the mice lacking macrophages. This means that, without neutrophils, nerve cells could not clearly cell debris properly even if macrophages were present; this strongly suggests neutrophils are of primary importance here.

Conclusion

This discovery could pave the way for new therapies designed to repair nerve cells damaged by neurodegenerative diseases, such as Alzheimer’s and Parkinson’s. The clearing of cell debris following nerve injury is critical for proper repair and nerve regeneration, and this study has discovered the role of neutrophils in this process.

The potential for targeting neutrophils to boost the clearing of debris to promote nerve repair is obvious and could be achieved via the use of immunostimulant molecules, which are commonly used to treat chronic infections and immunodeficiencies.

The next step for the team will be to explore immunostimulant molecules and the relationship between neutrophils and other cells in the nerve regeneration process. The immune system is increasingly looking like it holds the key to effective tissue regeneration, and science is rapidly unlocking the secrets of these amazing cells.

Literature

[1] Lindborg, J. A., Mack, M., & Zigmond, R. E. (2017). Neutrophils are critical for myelin removal in a peripheral nerve injury model of Wallerian degeneration. Journal of Neuroscience, 2085-17.

The Societal Benefits of Rejuvenation Biotechnology

Recently, we have explored the benefits that rejuvenation biotechnologies promise to bring to ourselves and the people close to us. I would imagine that most people have no difficulty acknowledging these benefits, but even so, many people tend to focus on potential large-scale downsides of rejuvenation while neglecting entirely its benefits on society at large.

The following is a brief discussion of how, in my opinion, anti-aging biotechnologies would positively impact the whole of humanity—assuming they were widely employed, as they should be.

Doing away with useless expenses 

The reason retirement exists is simple: older people aren’t healthy enough to work and support themselves, so the State needs to pay them pensions. Expenditures for pensions have no other real utility than allowing old people to live decently; this is, of course, a noble goal in and of itself, but if old people were able to support themselves, it would be better for them—because they would enjoy a large degree of financial independence—and also for the State and thus society—because the money saved on pensions could be put to other uses.

Let’s also not forget that, as their health keeps deteriorating, older people need ever-increasing medical attention. Unfortunately, geriatric medicine isn’t able to restore their health or prevent it from worsening, thus it becomes less and less effective with the passing of time. All that can be achieved through geriatric medicine is modestly reducing suffering or postponing the inevitable; in this sense, expenditures for geriatric care are nearly useless.

What would happen if rejuvenation biotechnologies to stave off age-related diseases were widely available?

For one, older adults would enjoy more youthful health; in a best-case scenario, people could look forward to enjoying the same health as typical young adults irrespective of their actual ages. Naturally, we can’t expect age-related diseases to be fully eradicated overnight; rather, we should expect a gradual series of advances staving them off by longer and longer measures, until they will possibly be eradicated altogether. Accordingly, the need for geriatrics will gradually decrease and eventually disappear, together with the medical expenditures associated with it. I don’t suppose I need to make a case about how not having to pay for treatments that can’t make people healthier anyway is better than the opposite—and again, the money saved on geriatrics could be put to other uses; for example, it could be used to finance State-subsidised rejuvenation therapies.

Secondly, if rejuvenation biotechnologies gradually made people healthier for longer, and perhaps even for an indefinitely long time, then people’s ability to work would be preserved accordingly. This would translate into more wealth contributed to society and less wealth spent on pensions; people who work for longer can pay taxes for longer and don’t need State support for longer. This would certainly change the way social security works, but I guess pensions wouldn’t disappear altogether—there might be other things that make you unfit for work, and after thirty years of working, you might want to take relatively short break, and it would be nice if we gave everyone the chance to do so by granting them a pension for maybe a couple of years.

The idea of working for a longer time, perhaps even much longer, may sound unappealing to some. To be honest, if the choice was between working for only 30 to 40 years because then I’d be too sick to continue and working for 80 years always in good health, I’d definitely take the latter. Besides, if I disliked my job too much to want to do it for such a long time, I would most definitely not consider shortening my life to shorten the time spent in that line of work; simply changing my job, however easy or difficult it may be, seems more reasonable.

Speculations on how this all might work in the distant future would be a pointless exercise because we don’t really know how much different that future will be, and they would be outside the scope of this article anyway. All that matters is that, in the near future and today’s economic system, it would definitely be a good thing for everyone if we could save on pensions and geriatrics.

Transforming society for the better

It’s impossible to predict with certainty the effects of any disruptive technology over the long haul, but a concern granted to be voiced in a discussion about rejuvenation is that of social stagnation—i.e. the default assumption that old people hanging around for longer would hold back social progress because of their ‘old people mentality’.

Here I will not try to argue against the concern above; rather, I’m going to put forward the opposite scenario, one that not many seem to consider: society could benefit from longer-lived members. I’m not talking just about scientists or great thinkers who could actually speed up our progress on all fronts if they just had more time at their disposal; I’m talking about a population with ever-growing life experience, knowledge, wisdom, and a lot to teach to younger generations. (Just imagine how much better a parent you could be with a 120-year life experience as opposed to 30, for example.)

In my opinion, this scenario is even more plausible than its opposite, because there’s no real evidence that very long-lived yet physically and mentally perfectly healthy people would necessarily be conservative fossils just because they’re old. Yet, the gloom-and-doom scenario is often people’s first thought. I have a hunch that this might be just evolution at work, as an extra pinch of pessimism might have granted better survival chances than too much optimism back in the day, but I don’t want to stray from the topic.

Another possible beneficial side effect of longer lifespans might be improved foresight. It’s easy to neglect global concerns that might not affect us personally over the course of our 80-odd-year lifespans. Some of us do display sensible behavior and are worried about the kind of world we’re going to leave to the humanity of the future; yet, others don’t concern themselves with problems that might manifest only long after they’ll be gone.

However, if our lifespans were much longer than just 80 years, the consequences of our negligent behavior would stand far better chances of catching up with us; this might make even the least sensible of people think twice before behaving irresponsibly, and all of us would benefit from it.

Sure, it would be commendable if everyone was genuinely concerned about pollution, for example, for the sake of humanity as a whole rather than just for their own sake; however, regardless of individual motives, the end result would still be a better world for everyone. I guess we could be content with that, even if some of us contributed to it because they had personal stakes and not exactly out of the kindness of their hearts.

Lifespan.io Discord server icon.

The Discord Life Extension Server

We have been hard at work advocating, writing and supporting the development of life extension technologies, or as we call them, rejuvenation biotechnologies. During the course of our activities, we have found that many people new to the topic have lots of questions and are naturally curious about the science behind it.

As great as giving talks at events and shows about life extension is, nothing beats talking to people one-on-one so that they can share with us any concerns they may have, or ask questions that might be on their mind.

A place to be among like-minded people

Since we began we have been very keen to interact with people on a personal basis and foster an active and engaged community. To that end, we decided to create a life extension discord community where our fellow supporters of rejuvenation technologies and all people interested in science can meet and get to know each other. To us, this is also a place where we can be among like-minded people and rest from that constant pressure of a mainstream culture that life extension supporters often have to bear with.

We had already been using Discord operationally to coordinate LEAF/Lifespan.io activities (and it is great!), as well as in our personal lives for video gaming, so we knew it was a solid platform. With the recent introduction of video chat adding to the wealth of supported features it made sense to make Discord the home of life extension discussion. You can find our Discord life extension server here, and you are welcome to join us!

We have regular discussions about rejuvenation biotechnology, gerontology, aging, longevity, life extension, radical life extension, immortalism, how to extend our own healthspan, what geroprotectors to take, and other related topics. Yes, there are no restrictions on your ambitions or your desire to learn, we talk about all kinds of things that you might wish to discuss (including policies but not politics!) there. We are also planning some cool live events in the future too.

A place to get more involved

As well as discussion and events there is also the opportunity to get involved and join in with our activities and even become a volunteer. We sometimes post our “10 minutes to help Lifespan” activities that anyone can help with. If you are interested in taking a more active role in advocating for science while also acquiring new skills and testing your capacities in a new field, the friendly atmosphere on our Discord life extension server will help you begin.

We also share our views with our Discord community on the best approaches to engage and inform those new to the topic, discussing ways to speak with people about the typical concerns related to longer lives, from immortal dictators to overpopulation, and issues with human rights.

These tips might make your life a bit easier and could help you turn your friends into supporters. We believe that the more minds that are engaged in finding the path to healthy longevity for all, the better, and we are here to support you!

The Discord life extension server is the ideal place to introduce yourself, get to know the LEAF team and see how you might like to get involved, so what are you waiting for? Come and join us today!

Three Awesome Videos About Life Extension

There has been an increase in the level of interest in the field of rejuvenation biotechnology over the last few years. The recent entry of senolytic therapies that clear senescent cells from the body into human clinical trials have spurred even more interest in the field of late. Today we wanted to highlight three very important new videos that have been published on Youtube this week. Three awesome videos about life extension The first video published by the popular YouTube channel Kurzgesagt delves into the topic of repairing age-related damage in order to treat age-diseases and asks the question, should we end aging forever? We are delighted that our president Keith Comito was involved in the creation of this video and it is great to see such a high profile channel actively supporting the goal of rejuvenation biotechnology. We greatly appreciated the chance to contribute to the making of this video and would like to thank Kurzgesagt for giving us this opportunity and for sharing the topic with its audience of almost five million fans.
One thing we can face as advocates is opposition to the ideas of rejuvenation biotechnology and sometimes this opposition can even be hostile due to deep seated biases. It is tempting to believe that such vocal people represent the majority view of doing something about aging, but one look at the like to dislike ratio of the video clearly shows this is not the case. At the time of writing the Kurzgesagt video sits at over 2 million views with 109k likes to a tiny 1k dislikes. If one did not take this into consideration reading some of the comments could make you think that the ideas proposed are not popular. However, the data is clear, these people are very much the vocal minority with the bulk of viewers being open to the idea. This gives those of us working on the frontline a much-needed morale boost and shows us that a greater majority of people are supportive. You may also be interested to hear that there will be a follow-up video on Kurzgesagt in November which focuses on the strategies and approaches researchers are employing to bring the aging processes under medical control with the ultimate aim of preventing age-related diseases. The second video is by popular Youtuber CGP Grey who produces a range of thought-provoking videos. The video in question discusses the idea of death and why just because it is natural does not make it good or necessary. The video delves into life extension a bit more than the first video but was launched in conjunction with Kurzgesagt as a joint effort.
As with the previous video, the ratio of likes to dislikes is massively in favor of the view that death is a bad thing. This shows that the vocal few are in the minority. At the time of writing the video stands at 1.7 million views with 89k likes to a mere 6k dislikes. Finally, Thunk has also made a video about medicine and aging and how progress could eradicate age-related diseases. He even touches upon the idea of longevity escape velocity – meaning one could live healthily for an extended period beyond the norm due to being alive to benefit from the arrival of ever more advanced medicines such as rejuvenation biotechnology.
Conclusion
Videos like these are hugely important to engage the public about rejuvenation biotechnology and help people understand and consider the possibilities. Some of the people who watched these videos may go on to the join the community and lend their support to our efforts. We do not have to convince everyone of the merits of eradicating age-related diseases either, we just need to convince enough people. Videos like this can help to explain and popularize the idea and it is clear from the reception to them so far that many people are open to considering a better future. To that end, we have created a way to bring the community together and welcome those new to the topic and answer any questions they might have. We have an active Life Extension Discord server which we invite you to join, come along and talk about the exciting science and progress being made in the field and get to meet those working in the field. There are even opportunities to not only discuss but also get involved in advocacy activities if you want to make a difference.  

Why Eradicating Age-related Disease Could Benefit You and Your Family

As I wrote in a different article, rejuvenation biotechnology promises a range of benefits for individuals. Lest anyone thinks that’s all rejuvenation has to offer, I reckon it’s worth discussing other ways that this technology would benefit larger groups of people—namely, your friends and family. If you are rejuvenated, that’s all good for you, but is there anything good coming out of it for your dear ones? Oh, yes.

Two burdens relieved with a single shot

The ill health of old age is a formidable sword of Damocles looming over us all, and when it falls down, it typically does not hit just us; the elderly are certainly the primary victims, but their family are collateral casualties. When people lose their health and independence to aging, their families have to go through the pain of seeing their loved ones becoming more and more fragile, sick, dependent, perhaps even demented. Adding insult to injury, the troubles caused by aging don’t stop here, because a sick and dependent person needs looking after. Thus, the family of an elderly person needs to step in themselves to take care of their relative; if this is not possible, a nursing home is likely going to be the only option left.

Personally taking care of a sick elder is no joke. It requires patience, effort, and most of all, time. It’s a real challenge, especially so for people who have young kids of their own to look after. Let’s also not forget that it is emotionally very taxing.

The nursing home option may partly solve the problem, because there, somebody else does the caring for you, but telling your elders that you can’t take care of them any more isn’t the best feeling in the world, for you or for them. This can be a rather costly solution, too—and as much as every last penny spent to take care of a loved one is well spent, a typical family only has so many pennies, and just because they need them for grandpa, it doesn’t mean they can conjure money out of thin air.

As things stand, when we’re going to be old, our dear ones will be faced with the issues above; however, if a decent rejuvenation platform was in place by then, none of these issues would materialize, because we’d be healthy and independent in spite of our age. We would never be a burden on our dear ones, and the time we’d spend together would be quality time for us and for them.

Be there for those who care about you

Luckily for me, I’m still very far from that stage of life when all your friends of a lifetime keep dying. I like to think that there would be more than one person grieving for my loss, and I believe that would actually be the case for most of us. If we exclude few, rare scenarios, your friends, and family would probably rather have you alive and well than inside a coffin. Thanks to rejuvenation, your spouse, your children, your grandchildren, and your friends may benefit from your presence, life experience, and persona for a much longer time. This would be a benefit for you as well, because you could live through your 80s, 90s, and who knows how much longer, without having to bury a dear friend a few times a year.

Somebody think of the children!

Unlike what I discussed above, what follows is not an indirect benefit of your own rejuvenation for someone else; still, it may be a benefit for your dear ones that you may want to think about.

I certainly understand why we need to think of ‘the children’ specifically—they’re too young to take care of themselves. However, I say we should go a little further and care for them not only when they’re still children, but even later on; we should care for them as people. And your children, old or young, will always be your children; you spend a good chunk of your life protecting them and keeping them away from unnecessary suffering. Once they’re grown-ups, this is something they can do pretty much on their own, but they won’t be able to protect themselves from aging; nobody can do that. However, future children—future people—may never have to worry about their or anyone else’s aging, if we only put enough effort into rejuvenation research and advocacy today. Adults of today aren’t guaranteed to escape the grip of aging, but today’s children stand a much better chance. This, I think, is something we should all remember when we look at kids around us, particularly our own.

Why Rejuvenation Biotechnology Could Benefit You

I’m sure you’ve noticed that LEAF has been shouting from the rooftops for quite a while that rejuvenation biotechnologies need to happen, and we’re doing our best to make them happen as soon as possible. The job isn’t easy; the fact that numerous people still raise concerns about the idea doesn’t make it any easier, and we invest part of our time duly addressing those concerns.

Speaking of concerns, I’m a bit concerned that the discussion about what might go wrong or how to prevent this or that hypothetical problem might draw attention away from another, possibly even more important question: Why do we strive to make rejuvenation a reality? There’s not much point in doing something if it doesn’t yield any benefits, especially if that something requires as much hard work as this cause does; so, what are the expected benefits of rejuvenation?

The benefits are many; some are obvious, and some are less so. The ones I’ll discuss in this article are the ones I see as obvious—tangible, immediate benefits for the people undergoing rejuvenation.

Health

We’ve kind of made a rather big deal of this one, haven’t we? Rejuvenation, we have said time and again, is pretty much all about health. The causal link between biological aging and pathologies is well established, and even when we account for the few elderly who are exceptionally healthy for their age, we’re left with the obvious fact that the older you are, the sicker you are—and even the aforementioned exceptions aren’t in the best of shape.

To the best of my knowledge, the number of people who actively wish to be sick at some point tends to be fairly small; so, when you think that a truly comprehensive rejuvenation platform would allow people to maintain youthful health irrespective of their age, the health benefits of rejuvenation become crystal clear. To be honest, this benefit alone would be enough for me, and I wouldn’t even need to look into the other ones.

Independence

Frailty, failing senses, weakness, and diseases aren’t good friends of independence, but they are good friends of old age. That’s why nursing homes exist in the first place—to take care of elderly people who are no longer independent. Again, even the few exceptional cases who manage on their own until death don’t have it easy. Having people doing things for you can be nice in small doses, but having to have people doing things for you, not so much. Rejuvenation would eliminate the health issues that make the elderly dependent on others, which is a rather evident benefit.

Longevity

As odd as it may sound, longevity is really just a ‘side effect’ of health, because you can’t be healthy and dead. The longer you’re healthy enough to be alive, the longer you’ll live. Since rejuvenation would keep you in a state of youthful health, the obvious consequence is that you’d live longer. How much longer exactly is hard to say, but as long as you’re healthy enough to enjoy life, it’s safe to say that longevity would be a benefit; you’d have more time and energy to dedicate to what you love doing, and you could keep learning and growing as a person for an indefinitely long time.

You would not have to worry about the right age to change your job, get married, or start practicing a new sport because your health wouldn’t depend on your age, and the time at your disposal would not have a definite upper limit. If the first few decades of your life weren’t as good as they could have been for one reason or another, you would still have time ahead and a chance of a better future, which sounds more appealing than ten years in a hospice with deteriorating health to me. (Let’s face it: If your life isn’t very good to begin with, a disease is hardly going to make it better.)

Additionally, a longer life would allow you to see what the future has in store for humanity. I wouldn’t be too quick to think the future will be all doom and gloom: Today’s world is more peaceful and prosperous than it was in the past, and while there’s no certainty it will be at least this good in the future, there’s no certainty that it won’t be worth living in either. I would argue it’s best not to cross our bridges before we get there, and we shouldn’t opt out of life before we actually reach a point when we don’t care for it anymore, if ever. I don’t think I will ever have a reason to give up on life or get bored with it, but I accept that somebody might think otherwise. Even so, I think being able to choose how long you want to live, and always living in the prime of health, is a much better deal than the current situation of having a more-or-less fixed lifespan with poor health near the end.

Choice

Ultimately, all of these perks can be summarised into one: choice. If we had fully working rejuvenation therapies available and were thus able to keep ourselves always perfectly healthy, regardless of our age, we could choose whether we wanted to use these therapies or not. Those who wish a longer, healthier life could avail themselves of the opportunity and escape aging for as long as they wanted; those who prefer to age and bow out the traditional way could just as easily not use the therapies.

Rejuvenation would give us an extra option we currently don’t have; everyone is forced to face the burden of aging and eventually die of it, for the moment. Being able to choose what we wish for ourselves is one of the most fundamental human rights and an obvious, unquestionable benefit.

Cytomegalovirus the Enemy Within

Cytomegalovirus (CMV) is a β-herpesvirus that infects the majority of people in the world, lying dormant and waiting for an opportunity to strike. This persistent virus remains in people for their entire lives once they are infected. it is thought that CMV contributes to microbial burden as we age, and our dwindling immune cell populations are tied up keeping it under control.

Today, we are going to have a look at what CMV is, how it works, and what we can do about it.

Cytomegalovirus, the dormant timebomb

CMV is part of the β-subfamily of herpesviruses, a family of viruses that are believed to have been co-evolving with their hosts for around 180 million years[1]. CMV infection is asymptomatic, meaning that it produces no symptoms and is a latent infection; in other words, it lies dormant in the cell awaiting activation under set conditions[2].

Reactivation from this dormant state is believed to happen periodically and so requires constant, lifelong immune surveillance to keep the body free from disease. Patients who have compromised immune systems are at greater risk for CMV reactivation, and this can lead to an increase of morbidity and mortality[3].

CMV is spread primarily via exposure to infected secretions and subsequent mucosal contact, which then acutely infects various cell types. After this acute infection, the virus spreads and then becomes dormant throughout the body.

In order to reactive and awaken from this dormant state, CMV, like all herpesviruses, progresses through an ordered cascade that starts with the expression of intermediate-early genes, which serve as a trigger for further (early and late) viral gene expression[4]. Studies have shown that CMV periodically expresses these intermediate-early genes at random during its dormant (latency) period[5-6]. This means that there is always a background level of CMV reactivation.

Once these initial genes are expressed, the cycle moves to express genes for host manipulation, DNA replication, and viral packaging. The expression of the intermediate-early genes is closely linked to proinflammatory transcription factors, such as Nuclear Factor Kappa beta (NF-κB), TNFα and interleukin-1β. Not surprisingly, these inflammatory signals can reactivate CMV as a result of this link[7-8].

So in this manner, CMV is sensitive to its environment, and its activity is regulated by local inflammatory factors. This means that injuries and other sources of inflammation can reactivate CMV from its dormant state just by the presence of inflammatory signals, and it uses this inflammation as a way to further reproduce and spread.

What can we do about CMV?

Even in people with healthy immune systems, constant CMV reactivations are potent stimulators of CMV-specific T cells. Perhaps more intriguingly, recombinant CMV viruses are currently being explored as a potential basis for vaccine vectors. A recombinant virus is a virus produced by recombining pieces of DNA using recombinant DNA technology.

This may be used to produce viral vaccines or gene therapy vectors. These vaccine vectors can then be used to generate large numbers of T cells against infectious diseases and cancer. Some CMV-based vaccines have been tested in nonhuman primate models of HIV infection [9-10].

A number of studies show that T cells play a crucial role in the control of CMV and prevent it from reactivating from its latent state by suppressing the viral gene expression cascade discussed earlier[11]. As we age, the numbers of T cells we have dwindle, so this suppression almost certainly dwindles as we get older.

Various studies have shown that adoptive therapy can restore CMV immunity, reduce the risk of CMV infection and treat infections resistant to antivirals[12]. Infusions of CMV-specific T cells can restore CMV-specific immunity in people[13], and, likewise, adoptively transferred (cells from either the patient or another person) T cells have also been shown to be able to control the spread of CMV[14].

This means that transferring CMV-specific T cells to infected patients could be a potential approach to dealing with CMV and could quickly restore immunity and prevent CMV-related deaths.

Controlling the spread of the virus is critical because CMV has been shown to tie up a huge number of T cells devoted to suppressing it in the circulation of infected adults[15]. This large number of required cells is likely due to the systemic nature of the virus and the fact that the immune system has to have CMV-specific T cells everywhere in order to keep it suppressed.

Conclusion

A huge amount of your immune system is devoted to keeping CMV in check, and as we age, that is a losing battle. Finding a way to destroy CMV could be very beneficial indeed to the immune system, as it would free up resources to fight other infections.

Adoptive immunotherapy is a promising approach in this respect, and with our ability to produce essentially unlimited numbers of CMV-specific T cells outside the body in culture for transplant, it might be the ideal solution.

Literature

[1] McGeoch, D. J., Cook, S., Dolan, A., Jamieson, F. E., & Telford, E. A. (1995). Molecular phylogeny and evolutionary timescale for the family of mammalian herpesviruses. Journal of molecular biology, 247(3), 443-458. [2] Fields, B. N., Knipe, D. M., Howley, P. M., & Griffin, D. E. (2007). Fields virology. 5th. [3] Crough, T., & Khanna, R. (2009). Immunobiology of human cytomegalovirus: from bench to bedside. Clinical microbiology reviews, 22(1), 76-98. [4] Hermiston, T. W., Malone, C. L., Witte, P. R., & Stinski, M. F. (1987). Identification and characterization of the human cytomegalovirus immediate-early region 2 gene that stimulates gene expression from an inducible promoter. Journal of Virology, 61(10), 3214-3221. [5] Grzimek, N. K., Dreis, D., Schmalz, S., & Reddehase, M. J. (2001). Random, Asynchronous, and Asymmetric Transcriptional Activity of Enhancer-Flanking Major Immediate-Early Genes ie1/3 andie2 during Murine Cytomegalovirus Latency in the Lungs. Journal of Virology, 75(6), 2692-2705. [6] Henry, S. C., & Hamilton, J. D. (1993). Detection of murine cytomegalovirus immediate early 1 transcripts in the spleens of latently infected mice. Journal of Infectious Diseases, 167(4), 950-954. [7] Hummel, M., Zhang, Z., Yan, S., DePlaen, I., Golia, P., Varghese, T., … & Abecassis, M. I. (2001). Allogeneic transplantation induces expression of cytomegalovirus immediate-early genes in vivo: a model for reactivation from latency. Journal of Virology, 75(10), 4814-4822. [8] Cook, C. H., Trgovcich, J., Zimmerman, P. D., Zhang, Y., & Sedmak, D. D. (2006). Lipopolysaccharide, tumor necrosis factor alpha, or interleukin-1β triggers reactivation of latent cytomegalovirus in immunocompetent mice. Journal of virology, 80(18), 9151-9158. [9] Hansen, S. G., Sacha, J. B., Hughes, C. M., Ford, J. C., Burwitz, B. J., Scholz, I., … & Malouli, D. (2013). Cytomegalovirus vectors violate CD8+ T cell epitope recognition paradigms. Science, 340(6135), 1237874. [10] Hansen, S. G., Piatak Jr, M., Ventura, A. B., Hughes, C. M., Gilbride, R. M., Ford, J. C., … & Gilliam, A. N. (2013). Immune clearance of highly pathogenic SIV infection. Nature, 502(7469), 100. [11] Simon, C. O., Holtappels, R., Tervo, H. M., Böhm, V., Däubner, T., Oehrlein-Karpi, S. A., … & Reddehase, M. J. (2006). CD8 T cells control cytomegalovirus latency by epitope-specific sensing of transcriptional reactivation. Journal of Virology, 80(21), 10436-10456. [12] Nicholson, E., & Peggs, K. S. (2015). Cytomegalovirus-specific T-cell therapies: current status and future prospects. Immunotherapy, 7(2), 135-146. [13] Einsele, H., Roosnek, E., Rufer, N., Sinzger, C., Riegler, S., Löffler, J., … & Kleihauer, A. (2002). Infusion of cytomegalovirus (CMV)–specific T cells for the treatment of CMV infection not responding to antiviral chemotherapy. Blood, 99(11), 3916-3922. [14] Holtappels, R., Böhm, V., Podlech, J., & Reddehase, M. J. (2008). CD8 T-cell-based immunotherapy of cytomegalovirus infection:“proof of concept” provided by the murine model. Medical microbiology and immunology, 197(2), 125-134. [15] Sylwester, A. W., Mitchell, B. L., Edgar, J. B., Taormina, C., Pelte, C., Ruchti, F., … & Nelson, J. A. (2005). Broadly targeted human cytomegalovirus-specific CD4+ and CD8+ T cells dominate the memory compartments of exposed subjects. Journal of Experimental Medicine, 202(5), 673-685.

Longevity Promotion a Multidisciplinary Perspective

There’s no doubt that Dr. Ilia Stambler’s Longevity promotion: multidisciplinary perspective is a thorough book that all kinds of advocates of healthy longevity may find very useful. The book reads pretty much like a collection of academics papers, each dealing with a different aspect of the matter, including science, history, social and moral implications, legislation, and advocacy. Just like you would expect from an academic work, each section of this book is complete with exhaustive sources that will indubitably prove helpful should you wish to dig deeper into the topic being discussed.

The first section of the book focuses on advocacy, discussing typical concerns raised in the context of life extension, outreach material, and initiatives, and it offers suggestions for effective policies to promote aging and longevity research. The latter part of this section was one of the hardest for me to read since policies and legislation are not at all my strongest suit, but I do believe that professional lobbyists and advocates who have legal and regulatory backgrounds and wish to take action will find numerous ideas in it.

The longevity history section discusses the progression of longevity science during the last century. It was surprising to learn that quite a few well-established scientific disciplines of today, such as endocrinology, owe their existence to early efforts to create rejuvenation treatments. This section discusses other aspects as well, such as the holism vs reductionism controversy in the history of longevity research and the legacy of Elie Metchnikoff, a pioneering immunologist and microbiologist who can safely be regarded as the father of gerontology and made no mystery of his conviction that aging should be considered a disease and treated as such.

However, the topic I found most engaging was the historical evolution of evolutionary theories of aging; antagonistic pleiotropy, disposable soma, and mutation accumulation are all presented here, and their merits and shortcomings are discussed from a neutral perspective.

Readers who have religious beliefs or are otherwise interested in religious traditions may find the longevity philosophy section of special interest, for it explains how the pursuit of healthy longevity may fit in the context of the main monotheistic religions, often in surprising ways. Superficially, one might think religions should be against life extension, as it might represent an obstacle on the way of the afterlife or reincarnation, for example; yet, the author makes interesting points about how religious philosophies have strong connections to the pursuit of longevity, sometimes even encouraging it and presenting it as a worthy goal.

The fourth and final section of the book is a treatise on longevity science. It discusses possible intervention to ameliorate age-related conditions, the current state of research, and especially the importance of agreeing on a diagnostic framework for aging. As the author himself points out, it is impossible to cure that which cannot be diagnosed; therefore, the task of curing aging, or the diseases of old age, will be much harder without widely agreed-upon criteria to establish which biomarkers are the most reliable and what their optimal values should be. In absence of such parameters, it won’t be possible to effectively assess whether any rejuvenation therapy is actually doing its job or not, and Dr. Stambler rightly stresses this fact.

In closing of the fourth section, the reader will find a short discussion of several other resources for further reading.

As the author’s writing style is rather formal and academic, some readers may find this book a ‘heavy read’. The text may also appear slightly repetitive on occasion, but, in my perspective, this may well be a feature rather than a bug: Together with the content structure, it helps make each section of the book independent of the others. Readers may safely skip any parts in which they’re not interested and move on to what they find more appealing, without fear of missing out on any crucial bit of information.

Using Artificial Intelligence to Rapidly Identify Brain Tumors

The use of artificial intelligence and, in particular, machine learning is becoming increasingly popular in research. These systems excel at high-speed data analysis, interpretation, and laborious research tasks, such as image assessment.

One of the areas in which machine learning has been enjoying success is image recognition. Now, researchers have begun to use machine learning to analyze brain tumors.

Training a machine to recognize tumors

Primary brain tumors include a broad range that depends on cell type, aggressiveness, and development stage. Being able to rapidly identify and characterize the tumor is vital for creating a treatment plan. Normally, this is a job for radiologists who work with the surgical team; however, in the near future, machine learning will play an increasing role.

George Biros, professor of mechanical engineering and leader of the ICES Parallel Algorithms for Data Analysis and Simulation Group at The University of Texas at Austin, has spent almost a decade developing accurate computer algorithms that can characterize gliomas. Gliomas are the most common and aggressive type of primary brain tumor.

At the 20th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI 2017), Professor Biros and collaborators presented the results of a new, automated method of characterizing gliomas. The system combines biophysical models of tumor growth with machine learning algorithms to analyze the magnetic resonance (MR) imaging data of glioma patients. The system is powered by the supercomputers at the Texas Advanced Computing Center (TACC).

The research team put their new system to the test at the Multimodal Brain Tumor Segmentation Challenge 2017 (BRaTS’17), which is a yearly competition at which research groups present new approaches and results for computer-assisted identification and classification of brain tumors using data from pre-operative MR scans. The new system impressively managed to score in the top 25% in the challenge and was near the top rankings for whole-tumor segmentation.

The goal of the contest is to be able to take an image of the brain and have the computer analyze it and automatically identify different kinds of abnormal tissue, including edema, necrotic tissue, and areas with aggressive tumors. This is a little like if you took pictures of your family and used facial recognition to identify each person, only here the images are brain scans, and it is tissue recognition that must be done automatically by the computer.

The team were given 300 sets of brain images to calibrate their systems with; this is known as “training” in machine learning terms and is how the machine is taught to identify features.

During the last part of the contest, the researchers were given 140 new brain images from patients and had to identify the location of tumors and divide them into different tissue types. They were given just two days to do this; for humans, doing the job would be a monumental amount of work.

The image processing, analysis and prediction pipeline they used has two main stages: a machine learning stage assisted by humans, in which the computer creates a probability map for the target classes it needs to identify, such as whole tumor and edema, and a second stage in which these probabilities are combined with a biophysical model which represents how tumors grow; this serves to impose limits on analyses and aids correlation.

Using supercomputers to characterize brain tumors

The system used the supercomputers of TACC, so they could use employ large-scale nearest neighbor classifiers, a machine learning method. For every voxel, or 3D pixel in an MR image of the brain, the system tries to locate all similar voxels in the 300 brains it had previously seen during training to determine if an area of an image is a tumor or not.

This translates to 1.5 million voxels per brain image, and with 300 brain images to assess, the computer system had to look at half a billion voxels for every new voxel of the 140 unknown brains it had been given in order to determine if a voxel was a tumor or healthy tissue. This was possible thanks to the use of the TACC supercomputers and represents a huge amount of computing power.

Each individual stage in the analysis pipeline utilized different TACC computing systems; the nearest neighbor machine learning classification component used 60 nodes at once (each consisting of 68 processors) on TACCs latest supercomputer Stampede2. The Stampede2 supercomputer is one of the most powerful computer systems in the world, and Professor Biros and his team were able to test and refine their algorithm on the new system in the spring of this year. They were some of the first researchers to gain access to the computer, and they needed the sheer power to perform these highly complex operations.

The end result of having access to this power was that Professor Biros and his team were able to run their analysis on the 140 brains in less than four hours. They correctly characterized the data with an accuracy of almost 90%, which is comparable to human radiologists doing the job and in a fraction of the time. The process is also completely automatic once the system algorithms are trained, and it can then assess image data and classify tumors without any further need for human intervention.

The system is being installed at the University of Pennsylvania by the end of this year in partnership with project collaborator Christos Davatzikos, director of the Center for Biomedical Image Computing and Analytics and a professor of radiology at the university. While the system will not replace radiologists and surgical staff, it will help to improve reproducibility of assessments and could potentially lead to faster diagnoses.

Conclusion

This is yet another example of how machine learning is being employed in research and medicine, and the methods the team has developed here have the potential to go beyond brain tumor analysis. The system could be used for other medical applications of a similar nature though transfer learning, so the possibilities are fairly endless.

If you are excited about how AI and machine learning can change research forever, you may be interested in a related project on Lifespan.io. The MouseAge project is seeking support to develop a visual recognition and assessment system that will allow researchers to determine the age of mice without the need for invasive testing. If you are interested in helping us create a system that could speed up aging research and reduce animal suffering, check it out.

 

A Potential Path to Treating Inflammation-related Aging and Cancer

The link between inflammation, cellular senescence, aging, and cancer is a complex relationship, but a new study sheds light on how these four interact.

The light and dark side of inflammation and cellular senescence

Cellular senescence is a protective mechanism that helps us to stay healthy and avoid cancer by removing damaged and aged cells from the cell cycle while preventing them from creating damaged copies of themselves. Senescent cells are disposed of via a self-destruct process known as apoptosis.

However, cellular senescence has a dark side. As we age, the immune system slows down, becomes dysfunctional, and ceases to remove senescent cells, allowing them to accumulate.

The accumulation of senescent cells in aged tissues is a hallmark of aging and one of the processes that causes us to age[1]. As senescent cells build up, they trigger the immune system to generate excessive inflammation, which, in turn, impairs healthy tissue regeneration and drives the aging process ever faster.

This contributes to the smoldering and chronic age-related inflammation known as “inflammaging”. Other sources of inflammaging include microbial burden, cell debris and protein crosslinking. This chronic inflammation contributes to age-related diseases, including cancer, heart disease, and neurodegeneration.

The focus of current research efforts is to find ways to periodically remove senescent cells from the body using senolytic therapies or to reduce inflammation by manipulating the immune response.

Chromatin leaking leads to inflammation

A new study by researchers from the Perelman School of Medicine at the University of Pennsylvania found that chromatin – a structure in the cell nucleus where genes are housed – can become misplaced[2]. The traditional view is that chromatin as a cell component remains within the nucleus in order to regulate gene expression. However, the team found that there were misplaced chromatin fragments outside the nucleus that had been pinched off from nuclei present in senescent cells.

This misplaced chromatin causes a DNA-sensing pathway called cGAS-STING to become activated in its presence. The cGAS-STING pathway is based outside the nucleus and is known for its ability to combat microbial invasion from bacteria and viruses. It appears that in the case of cell senescence due to aging, the chromatin leaks outside the nucleus and triggers the cGAS-STING pathway, which reacts to this the same way it does to microbial infection. The leaking chromatin triggers an “alarm signal”, leading to inflammation.

Inducing short-term inflammation is useful in fighting infections and preventing cancers from developing; the problem begins when that inflammation becomes chronic, such as in aging. It leads to loss of tissue repair and ultimately can even help cancer spread.

The researchers used cellular stressors, such as DNA-damaging agents, activated oncogenes, and regular aging cells, to set off the alarm signal. They found that cells responded by shutting down and entering cellular senescence and calling the immune system to dispose of them. This depends on the immune system working properly, and while it is designed to clear away senescent cells, if uncontrolled, it can do more harm than good.

Sounding the alarm

The team observed that when mice with disabled cGAS-STING alarm pathways are exposed to cancer-inducing stressors, their cells do not summon the immune system for help. This is a problem because those damaged cells lead to the formation of tumors.

In normal mice exposed to stressors that induce aging, the accumulation of senescent cells causes a continual call for the immune system, leading to an excessive immune response and chronic, long-term inflammation. This then induces tissue damage, failure of tissue repair and premature aging.

Months after receiving stressors, the normal mice with an active alarm system showed masses of grey hair, a sign of aging in mammals, including humans. In contrast to this, mice lacking the alarm system had normal black hair, which shows exactly what the light and dark sides of cellular senescence are.

The researchers are now searching for molecules that target the always-on cGAS-STING alarm pathway in the hope of finding ways to manipulate the inflammatory response.

Conclusion

Science is steadily unraveling the exact mechanisms behind cellular senescence and how it contributes to chronic inflammation and aging. Of the two approaches to dealing with senescent cell accumulation, the removal of them seems the more direct approach over attempting to mediate the inflammation by tweaking various pathways, as these researchers are attempting to do.

While we find out more about how this complex interaction plays out, there are human trials for senolytics launching this year, and some studies are already in progress in some cases. In our view, removing the root of the problem seems to to be the more practical approach than modulating the signals from senescent cells without actually removing them.

Literature

[1] López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194-1217.

[2] Dou, Z., Ghosh,K.,Grazia, M. et al. Cytoplasmic chromatin triggers inflammation in senescence and cancer. Nature (2017) doi:10.1038/nature24050.

 

The Good Sides of Aging?

Sometimes, and especially in articles aimed at mitigating people’s fear of aging, it is said that aging doesn’t come just with downsides, such as frailty and diseases, but also with upsides—for example, wisdom and a long life experience.

It is often subtly implied that these two very different aspects are two sides of the same coin, that you can’t have one without the other, and perhaps even that the ill health of old age is a fair price to pay for the benefits that also come with it.

Nothing could be further from the truth.

Setting the record straight

There are plenty of good reasons to be afraid of aging, because the diseases and disabilities it causes are very real and far from being observed only in exceptional cases. It would be foolish not to fear cancer, for example, because it is an extremely serious and often fatal condition; in the same way, and for the same reasons, it is foolish not to fear aging; perhaps, an even stronger fear is justified, because aging can and does give rise to many diseases, including cancer itself.

There’s nothing wrong with fearing aging, because it may help us steer clear from its inherent dangers, just like the fear of any other harmful thing keeps us away from it. This is true so long as by ‘aging’ we mean biological aging, which is not at all the same as chronological aging. It is very important to draw a line between the two so that we don’t end up accepting the downsides of the former, which are neither necessary nor sufficient to enjoy the benefits of the latter.

What’s the difference?

Chronological aging is a rather fancy term to indicate a very mundane thing, namely the passing of time. For as long as time will keep passing, everything will age chronologically. This is obviously a good thing because if time did not pass, the universe would stand still and nothing at all, including ourselves, would ever happen.

However, it is easy to see how chronological and biological aging are not the same thing by means of a simple observation: Although time runs essentially uniformly everywhere on Earth, different life forms have different health- and lifespans. If time passes at the same rate for me and for a cat, and yet I’m (biologically) old at age 80 while a cat is (biologically) old already at age 15, clearly there must be something else than just the passing of time that accounts for this discrepancy.

This ‘something else’ is metabolism—the intricate set of chemical reactions the bodies of living creatures perform on a daily basis for the very purpose of staying alive. As we have discussed in other articles, what we call biological aging is really just a process of damage accumulation; this damage, which eventually leads to pathologies, is caused by metabolism itself, and therefore a faster metabolism means faster aging. Different species have different metabolic rates; as a rule of thumb, the smaller the species, the faster its metabolism and thus its aging, leading to shorter health- and lifespan. This is, in a nutshell, why a cat ages faster than I do.

As a confirmation of this fact, one may observe that species in a regimen of caloric restriction tend to live longer (sometimes much longer) than their normal lifespan, and the insurgence of age-related diseases is delayed accordingly: A lower caloric intake causes metabolism to slow down; consequently, the aging process follows suit.

Interestingly, some lucky species, the so-called negligibly senescent organisms, don’t show any signs of biological aging at all with the passing of time.

At this point, you don’t have to be clairvoyant to see that biological aging implies chronological aging, but not vice-versa. No chronological aging means no time passing, and no time passing means nothing takes place, metabolism included. However, since different creatures age differently (or not at all) despite time passing at the same rate for all of them, chronological aging doesn’t imply biological aging. Quite simply, they’re not the same thing.

Render unto Caesar the things which are Caesar’s

Having cleared the difference between chronological and biological aging, we must now correctly attribute the aforementioned pros and cons of old age to each of them.

From the very definition of biological aging above, it’s clear that it is the culprit responsible for the cons—the diseases of old age.

Speaking of the pros, all possible benefits of old age—life experience, wisdom, sense of accomplishment—certainly do not come from the damage that metabolism has wrecked throughout your body over the years. Clearly, they depend on the events of your life, and thus they’re not at all granted to happen, no matter how long you live. If you spent your life in isolation doing nothing, avoiding new experiences and not learning anything new, your wisdom as an eighty-year-old would hardly compare to that of a well-traveled, seasoned scientist or philosopher of the same age, for example. Ultimately, the benefits traditionally attributed to old age obviously depend on the passing of time (i.e., chronological aging), and most of all on the use you made of your time. Just because you’re old, you’re not automatically wise, accomplished, or well-learned.

What’s more, the debilitation that comes with biological aging makes it harder for you to relish and expand the wisdom and experience you’ve accrued over the years. So, not only does biological aging bring no benefits; it is a hindrance as well.

In conclusion, the pros and cons of old age are due to different causes, and, as such, they aren’t interdependent. The diseases of old age are not a currency you can use to buy yourself the wisdom of the aged, and thanks to the emergence of rejuvenation biotechnologies, you might relatively soon be able to enjoy the pros of old age without having to pay any undue and unfair tolls.