Recently, Dr. David Sinclair did an AMA (“Ask Me Anything”) on Reddit. Events like these, which allow people to ask researchers questions about their work on an open forum, can often turn up interesting responses that are not always uncovered during interviews.
We have picked these few questions and answers, but we suggest that you visit the Reddit AMA thread to read more.
Do you see the field of aging research converging toward a unified theory of aging? I notice a lot of similarity between your information theory of aging and the somatic restriction theory proposed by Dr. Michael West, for example.
Exactly. Michael and I recently spent an afternoon together brainstorming. It does feel like we are making progress.
What particular things do you think will be bottlenecks in the practical application of longevity research that could use more people in the near future and that would be most worth trying to break into?
The main impediment is that aging is not something doctors are inclined to treat. Why? Because aging is not yet defined as a disease or even an ailment by regulators, even though it’s the main cause of disability and disease. It’s considered “natural”. If this were to change, and aging was defined formally as a medical condition (as suggested by WHO), then doctors could more easily feel comfortable prescribing medicines that slow aging to people over a certain biological age instead of waiting until it’s too late.
Other things to do are to educate doctors, do research in this area, and help increase funding of aging research and development. Getting the word out is a good start. Thanks to everyone who has made it a topic of discussion among friends and colleagues.
How are NAD levels measured in an animal?
We measure NAD in blood and tissue. In humans, blood. There are a few ways to do it. Fluorescent assays and liquid chromatography are the most convenient. Mass spectrometry is another level up. We use Mass Spec in our Cell 2007 paper, but it’s not easy.
What do you look for when selecting new members for your lab?
Lab members have to be 1. Good people/trustworthy 2. Energetic 3. Passionate 4. Undergrad in biology or computing or engineering 5. Good communicator 6. A thumbs-up from all lab members. Experience in a lab helps.
Do you think there is a significant difference in sublingual vs oral administration of NMN?
I’ve not seen a head-to-head comparison. Don’t know if there’s an advantage to one or another. We all need to be data-driven. Someone should publish a study if they’ve done one. I can tell you that oral NMN can raise NAD levels in the bloodstream of mice and people.
Would you be kind and briefly summarize at what point we are in the process of research? What is the main focus? What are the recent discoveries? Where would we be in the next 5 years?
We are at the same stage as the Wright Brothers. We’ve built a glider that works well. We have engines we are strapping on. We know it’s possible. We have seen birds fly. The main focus is finding ways to turn on longevity genes, what is the effect of combining them, how to delete senescent cells, and epigenetic reprogramming. In the next 5 years, I hope to see medicines available based on this research. Hard to know what will be first. I hope to have reversed aging in the eye to restore vision.
What sort of scientific breakthroughs do you think we would need in order to restore an epigenetic state from significantly earlier in life (e.g. that of a 25 year old, when you are 50). A study by Stölzel et. al in 2017 initially showed a significant decrease in DNA methylation age following transfusion of a hematopoietic stem cell transplant but later resulted in a return to ‘correct’ age and an accelerated rate of epigenetic aging. This suggests that the ‘signal’ of the age-appropriate genome is stronger than that of exogenous tissue (at least in HSCs) and could pose a barrier to restoration of epigenetic information from earlier in life. Are the mechanisms behind this going to remain a thorn in our side for decades, or do we already know a few things that could be used to mitigate it?
Tough question. We are going to test what happens to a mouse when you reprogram it whole body. Juan Carlos Belmonte’s work suggests it can work. I’d be surprised if there is a rebound against reprogramming – we are first verifying this in mouse eye reprogramming experiments.
I’m wondering what the current state of the 3/4 Yamanaka factors treatment is? It was pretty exciting to hear about the nerve regeneration, so I’m hoping that that comes to fruition soon.
Also, presuming it is a generally safe and effective treatment for humans, what kind of measures will be needed to apply it? It’s fairly hard to do a full genetic rewrite on live animals, so I’m hoping an injection or other method would be a safe method of application rather than having to modify the next generation to have triggerable regeneration.
I’m amazed how many people have read our paper already. What an interesting world we live in. I hope to publish in a journal soon so the wider scientific (and lay) world can hear about it…thanks for the kind words. We are blown away by the results.
It would be an injection. AAVs are getting better every year. We are now testing new AAVs and delivery methods as well as molecules that could be ingested. (I really hope no one tries this at home).