This week on Lifespan News, Brent Nally discusses a life extension drug discovered by accident, a recent report on evolution and maximum age, CRISPR gene editing on human patients, and a method of treating dementia slated to be tested in humans.
Further Reading
Life Extension Drug Discovered by Accident
Evolution Won’t Stop Aging Any Time Soon, but Medicine Might
Intellia Shows CRISPR Gene Editing in Humans Has Arrived
Success in Reversing Dementia in Mice Sets the Stage for Human Clinical Trials
Script
An off-patent osteoporosis drug turns out to have an unexpected side effect: it may extend lifespan. You’ll find this story and more in this episode of Lifespan News.
Welcome to Lifespan News on X10, your source for longevity science updates. I’m your host, Brent Nally. We encourage you to check the description below for links to these stories.
For our first story, a life extension drug has been accidentally discovered. Researchers have found that an off-patent drug used to treat osteoporosis called zoledronate has unexpected life-extending properties in humans. The researchers confirmed these findings in a fruit fly study. Zoledronate is used to strengthen bones and reduce the risk of osteoporosis-related bone fractures. A 2010 study had found that people who were given zoledronate after experiencing hip fractures showed slightly reduced all-cause mortality compared to a control group. Now, new research has dug deeper into this. First, the team administered zoledronate to fruit flies early in life. The researchers found that the lower zoledronate dose improved the lifespan of male flies but did not aid females; rather, the higher dose significantly decreased their lifespan instead. However, the lifespan in both male and female middle-aged fruit flies increased when the researchers administered zoledronate, increasing male lifespan by roughly 5% and female lifespan by 16%. The team noted that these results are similar to rapamycin, but they confirmed that the increase is independent of caloric restriction. The researchers were also able to identify the enzyme inhibited by zoledronate to increase lifespan. This gives a pretty solid picture of how it works, but these are still just initial findings in a single model species. More work will be needed to see if the effect holds in mammals, and perhaps to identify other drugs or mechanisms to affect the same pathway.
Lifespan.io is excited to announce our fourth annual Ending Age-Related Diseases conference which is scheduled to take place August 19th to 22nd, 2021. We’ll be meeting virtually to learn the latest developments from leading bio rejuvenation experts.You can register at lifespan.io/conference which is also linked in the description below.
For our next story, evolution won’t stop aging any time soon, but medicine might. A new study about the ‘invariant rate of ageing’ has led to reports that aging is unstoppable. However, this reporting is based on a misunderstanding of what the study actually states. The study aimed to investigate the ‘invariant rate of aging’ hypothesis, which proposes that the rate of aging is fixed within a species. The idea is that aging has evolved in concert with a suite of other traits, such as birth rate and metabolic rate, and this concerted evolution has led to the rate of aging being relatively fixed within a species. To test this hypothesis, the researchers created a statistical model of the age-specific risk of death in species from seven primate genera. The researchers used data from various studies to set the parameters of their model, which is how they tested the amount of variation. The study’s first finding is that most of the gain in human lifespan so far has come from reducing mortality at younger ages. There’s also variation in the infant and juvenile mortality parameter, both between societies and at different times. Unlike the infant and juvenile mortality parameter, the senescent mortality parameter varied very little within each species. In fact, changing this parameter in their model shifted the mortality and demographic data of one species to look like another. Therefore, this study does not show that the rate of aging cannot be changed; rather, this study shows that there’s a limit to how much change can be realized without biological interventions, which is precisely the challenge that longevity research aims to overcome. These reporters seem to have gotten tripped up on the idea of an ‘invariant rate’, which has the key implication that biological constraints determine the rate of human aging. This led to the conclusion that aging is fixed, inevitable, and immutable, but that’s not at all what the study shows, as the paper itself directly states. The paper itself closes on that note, though you wouldn’t know it from the way it’s been covered. “It remains to be seen if future advances in medicine can overcome the biological constraints that we have identified here, and achieve what evolution has not.”
For our final story, success in reversing dementia in mice sets the stage for human clinical trials. Researchers have identified a new treatment candidate that appears to not only halt neurodegenerative symptoms in mouse models of dementia and Alzheimer’s disease, but also reverse the effects of the disorders. In an earlier study, the team found that the SAK3 molecule, which is involved in calcium channels, enhanced the function of a cell membrane channel and promoted neuronal activity in the brain. When the Ca2+ channel is dysregulated in the brain, the acetylcholine and dopamine releases are reduced. The result is a dysregulated system that a person experiences as cognitive confusion and uncoordinated motor function. SAK3 directly binds to the subunit of this channel, resulting in the enhancement of neurotransmission thereby improving cognitive deficits. The researchers found that the same process also appeared to work in a mouse model of Lewy body dementia, which is characterized by a build-up of proteins known as Lewy bodies. SAK3 also helps manage the destruction of misfolded alpha-synuclein. Normal alpha-synuclein helps regulate neurotransmitter transmission in the brain. The protein can misfold and aggregate, contributing to what researchers suspect may be an underlying cause of neurodegenerative symptoms. This aggregation can also lead to the loss of dopamine neurons, which help with learning and memory. According to one of the authors, Kohji Fukunaga, SAK3 enhances the activity of the system that identifies and destroys misfolded proteins. In neurodegenerative diseases, the system is often dysfunctional, leaving misfolded proteins to muck up the cell’s machinery. Fukunaga states, “SAK3 is the first compound targeting this regulatory activity in neurodegenerative disorders. SAK3 administration promotes the destruction of misfolded proteins, meaning the therapeutic has the potential to solve the problems of diverse protein misfolding diseases such as Parkinson’s disease, Lewy body dementia and Huntington’s disease, in addition to Alzheimer’s disease.”
That’s all the news for this episode. Is there a recent life extension story that you think we should have covered but haven’t yet? And what was your favorite story from this episode? Let us know what you think in the comments and we’ll see ya in the next episode.
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