David Sinclair recently published a new book to assist in publicizing his present research directions, companies, and thinking on aging, and is here interviewed by the Life Extension Advocacy Foundation (LEAF) volunteers. The work presently underway includes supplements to increase levels of NAD+ in mitochondria and, separately, partial reprogramming of cells in a living individual in order to gain some of the effects of full reprogramming, particularly restoration of mitochondrial function. Fully reprogramming cells into induced pluripotent stem cells has been shown to clear out dysfunctional mitochondria and reset epigenetic markers of age to a more youthful configuration.

It is worth noting that this strategy will not be able to fix a great many of the issues that arise in cells with age, such as the accumulation of metabolic waste that even youthful cells cannot break down effectively. If it can be used to safely restore mitochondrial function in old tissues for an extended period of time, however, then that is certainly interesting enough to chase aggressively in and of itself. Mitochondrial dysfunction is a noteworthy aspect of aging, and is involved in numerous age-related diseases.

Currently, medicine treats the symptoms, not the causes, of age-related diseases. Do you think that we might soon reach the point where therapies will be taken in a preventive manner to delay the onset of age-related diseases?

Well, there's a subset of the population, particularly in the US, but increasingly around the world, who are using the internet to educate themselves and are trying to take action before they become sick. Sometimes with medical supervision, sometimes not. It's a grassroots movement right now; for it to become mainstream, the regulations would have to change so that doctors can feel comfortable prescribing medicines to prevent diseases. But, if we don't change, then we will continue to practice whack-a-mole medicine and only treat one disease at a time after it's already developed.

You are very well known for your work with NAD+ and its precursors; we're often asked whether nicotinamide riboside or nicotinamide mononucleotide is better?

They're very similar molecules, and both have been shown to provide a variety of health benefits in mice. That doesn't mean either of them will work to slow aging in humans, and that's why placebo-controlled clinical trials are required to know if one of them, or both of them, will work in certain conditions. Those studies began over a year ago, and they are currently Phase 1 safety studies in healthy volunteers. Next year, the plan is to test the pharmaceutical product in a disease area, most likely a rare disease, but also in the elderly to see if we can recapitulate some of the results we've seen in mice, such as increased blood flow and endurance.

Another area that you are involved in is partial cellular reprogramming to reverse age-related epigenetic alterations in cells and tissues. Please tell us a little bit about this approach and the approach that you are taking and how you're progressing so far?

For 20 years, we've been working on epigenetic changes as a cause of aging, starting with work in yeast and now in mammals. We've developed viral vectors and combinations of reprogramming factors that appear to be much safer than past approaches, and we've used them to reprogram the eye to restore vision in mice with glaucoma and in very old mice. Currently, it is believed that the epigenetic clock is just an indicator of age and not part of the actual aging process, but our recent work strongly suggests that the process of reversing the clock doesn't just change the apparent age of the body, it actually reverses aging itself by restoring the function of the old cells to behave as though they're young again. Therefore, the clock may not just be telling time; it may actually be controlling time.

Could you please tell us a little bit about your book and what the readers should look forward to?

"Lifespan: Why We Age and Why We Don't Have To" takes the reader on a journey through history, looking at the endeavor of humans to try to live longer and using that historical perspective to look at today's situation and project into the future. The book also takes readers on a journey through the very cutting edge of aging research and things that the reader can do right now to take advantage of these new discoveries in their daily lives with changes in their daily activity, what they eat, when they eat, but also medicines that are currently available on the market that may extend lifespan. The last chapter is about where we are headed, what are the medicines that are in development, and then when these drugs become available, what does the world look like? Is it a better place or a worse place, and how will our lives change?