A Look at the Work of David Sinclair

This article paints a picture of David Sinclair as one of the important researchers in the move towards treating aging as a medical condition. I'd say that he's certainly good at publicity and fundraising, and has more than done his part to make drug development for the treatment of aging plausible in the eyes of the public, but it is a pity that all of this is coupled to lines of research (such as the investigation and manipulation of sirtuins) that to my eyes have no hope of producing meaningful therapies. Even if sirtuin-based therapies could do all that the original hype promised, the end result would be a marginal, slight slowing of the aging process. As an end goal for the investment of billions and years of time, that simply isn't worth it when there are far better approaches to the problem such as SENS that can in principle lead to actual rejuvenation and the addition of decades of healthy life.

Today, Sinclair's work on slowing the ageing process, and even reversing some aspects of it, could lead to the most significant set of medical breakthroughs since the discovery of antibiotics nearly a century ago. At the heart of what motivates him is a deceptively simple notion: if the greatest driver of disease in old age is old age itself, then why not find a cure for ageing, which he describes as being "the greatest problem of our time". Sinclair's statement is borne out by the World Health Organisation's Global Burden of Disease Project, which estimates that the number of years lost to premature death or compromised by disability in 2010 was 2.5 billion, meaning that about a third of potential human life goes to waste. The toll from crime, wars and genocides does not come close to matching this. Yet, as Sinclair points out, just one per cent of medical research funding is spent on understanding why we age and even less on doing something about it. His goal is to find the "master control switch" that can regulate the pathways that contribute to ageing itself. "It could be one pill for 20 diseases at once. It would be the most profitable drug ever made."

Extending the generally accepted limits of human life is now being taken seriously by some of the world's top scientists. Backed by wealthy philanthropists and tech giants such as Google, billions of dollars are being poured into longevity research. Press releases and PowerPoint presentations come laced with terms such as health-span, not lifespan. The elderly, we are told, will become the wellderly. There will be fewer bedridden geriatrics taxing our overstretched medical systems. The ever-growing list of billionaires funding research into longevity includes PayPal co-founder Peter Thiel, who has set up Breakout Labs, a non-profit organisation that supports early-stage companies, and Oracle founder Larry Ellison, who has donated more than $US430 million ($600 million) to anti-ageing research.

Sinclair is decidedly reticent when it comes to passing judgment on the work of other scientists such as Craig Venter at Human Longevity Inc. and Cynthia Kenyon at Calico: "I think it's going to take a lot of resources to find the needle in the haystack, but it's helpful that more people are getting involved in ageing research. If Craig and his associates tackle it from the sequencing side and we tackle it from the fundamental biology side and Google's Calico attacks it from bioinformatics side, then there's more chance of finding the right medicines." Circumspection is embedded in Sinclair's DNA. He speaks slowly and deliberately, giving his audiences time to absorb both the complex science behind his discoveries and to underline what motivates him. "How sad would it be if we, after 10,000 generations, we were the last ones to live a normal lifespan? Imagine if we were born one generation too early to reap the benefits of this technology."

Link: http://www.smh.com.au/interactive/2015/never-say-die/


"His goal is to find the "master control switch""

There is no "master control switch". There is no "needle in the haystack", either. He has to know this, so he's either cynically lying because he plans on using the money to fund real therapies, or he's cynically lying to fund worthless sirtuin bullcrap, and it's likely to be the latter.

Posted by: Slicer at October 5th, 2015 12:43 PM

Agree with reason this is pointless. I notice he has a project on lifespan.io but I will not donate, it's a waste of time for little gain. It's reseveratrol again.

Posted by: Steve h at October 6th, 2015 12:06 AM

While I might agree that Sinclair has wasted time and money on just one facet of the aging cascade process, it would be interesting to see the results of the SENS efforts in terms of actual results in comparison. At this point from a results (actual therapeutics with proven clinical performance) perspective - I'm not seeing much difference.

Posted by: Mason Hamilton at October 11th, 2015 10:18 AM

There ARE master epigenetic switches via gene networks: AMPK, NFKAPPA-B, mTOR, KLOTHO, PARP-1, Sirtuin1, Sirtuin3, Nrf2, FOXO, Pgc1a, HIF-1, all which by the way are all favorably switched by resveratrol and other polyphenols. At issue is whether anti-aging agents can overcome a bad diet or whether a limited calorie or low-carbohydrate diet (low carbs comprise 71% of the benefit of a CR diet) is required to go along with it? Certainly an anti-aging pill should not end up giving license to eat Twinkies. If there is no master switch, then tell that to MIT that developed and introduced their own anti-aging NAD pill. In effect, Harvard + investors was paid over $700 million by a pharmaceutical company just to take a micronized resveratrol pill off the market. You don't mean to say that resveratrol was worthless do you? The rub against resveratrol is that it only worked in high-fat fed mice but fat has now been dismissed as the metabolic killer, carbohydrates and refined sugar are now identified as the nemesis. Lots more to think about. Sinclair's work is not fruitless, just not commercially palatable for Big Pharma. Sinclair has said any day this technology (CR mimetics) are utilized, this all will become real. Metformin is posed an an anti-aging pill of sorts, primarily by activation of AMPK, yet resveratrol activates AMPK 50-200 fold better. Re-think. Researchers have not abandoned resveratrol research.

Posted by: Bill Sardi at October 11th, 2015 11:13 AM

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