Genetics and Aging Venture Human Longevity Launched

Technological progress happens in waves, and this is just as much the case in longevity science as elsewhere. Ideas spread within a community, and are acted upon by diverse groups around the same time. Funding is found, companies and laboratories are established, work is accomplished across a few years, and in the course of that new ideas arise. A few more years pass as new connections are forged and the new ideas digested, and then the cycle starts anew. This takes around a decade or so in a fast moving field, and we are, I think, at that overlapping time of the end of the current cycle and the beginning of the next.

The last cycle of development and research included the creation of the SENS research programs and the Methuselah Foundation, attempts to apply sirtuin research and the rest of the first batch of unsuccessful attempts to build calorie restriction mimetics, a great sea change in research community attitudes towards longevity science, and took place over a period in which the tools of genetics have shifted abruptly from costly to cheap.

Given a growing acceptance of the prospects for treating aging to extend healthy life, and the plummeting price of DNA sequencing and genetic engineering, it seems that we will see new large-scale initiatives established at the intersection of genetics and aging. My suspicion is that this is where Google's Calico venture will spend much of its time, for example. Hopefully I will be proven wrong on that count, however. It strikes me that outside of very narrow and specific applications of genetic engineering - such as the SENS approach of allotopic expression to eliminate mitochondrial damage as a cause of aging - focusing on gene sequencing in the context of life extension is very much a case of searching for the keys where the light is good, not in the dark where you dropped them.

Based on the large amount of data accumulated to date on the genetics of longevity, we should expect it to be a very complex domain. There will be thousands of contributing genes, every one of which has a tiny, near-insignificant effect on its own, an effect which is very dependent on other variations, and which will be different in every regional population and lineage. With very few exceptions, it has proven challenging to reproduce associations noted between specific genetic variations and human longevity: the association in one study population is non-existent in others, and wasn't large at all to begin with.

Similarly, manipulation of epigenetic patterns, the decorations on our genes that determine whether and how much of a protein is produced from its genetic blueprint, and which change rapidly in response to circumstances, is also an enormously complex undertaking. It is an extension of targeted drug discovery, really, where researchers aim for ever more precise ways to change the expression of specific genes so as to produce beneficial effects. Given so far unsuccessful struggle of the past decade to try to recapitulate even just a fraction of the benefits of the known and cataloged epigenetic changes that accompany calorie restriction - something that is not expected to extend life in humans by much more than five years - I'm not anticipating great benefits to longevity to arise from this path ahead, or at least not soon enough to matter.

But genetics is cheap now, and while human longevity may not benefit greatly over the next few decades, many other aspects of medicine will. So people will try:

In Pursuit of Longevity, a Plan to Harness DNA Sequencing

Dr. Venter announced on Tuesday that he was starting a new company, Human Longevity, which will be focused on figuring out how people can live longer and healthier lives. To do that, the company will build what Dr. Venter says will be the largest human DNA sequencing operation in the world, capable of processing 40,000 human genomes a year. The huge amount of DNA data will be combined with other data on the health and body composition of the people whose DNA is sequenced, in hopes of gleaning insights into the molecular causes of aging and age-related illnesses like cancer and heart disease.

Slowing aging, if it can be done, could be a way to prevent many diseases, an alternative to treating one disease a time. "Your age is your number one risk factor for almost every disease, but it's not a disease itself," Dr. Venter said in an interview. Still, his company will also work on treating individual diseases of aging as well. Human Longevity said it had raised $70 million, most of it from wealthy individuals, some of whom have backed his existing company, Synthetic Genomics.

My comments above aside, a rising tide floats all boats. If the next ten years brings ever-greater legitimacy for longevity science, and ever-greater public support for the goal of eliminating age-related disease from the human condition, then I'm fine with that even if a lot of the participants are barking up the wrong tree, or taking the slow and expensive road that generates data and little else.

As I note with great regularity, we don't actually need a complete understanding of aging in order to effectively treat it. Developing that complete understanding will cost far, far more to than to simply act on what we know already: list the known root causes of degenerative aging and repair them. Given that the research community already has a well-defined list of the differences between old tissues and young tissues, we can skip the exceedingly complex and expensive part of development in which it is determined exactly and in great detail as to how these changes progress and interact with our biology. Researchers know what the changes are, and there exist plausible plans to develop the means to revert these alterations. More knowledge is always good, but it isn't strictly necessary, and certainly isn't as important as saving lives through a greater focus on implementation of clinical therapies.


I believe CR to be more of a quirk in the metabolic function of organisms than an evolved response to famine. The requirements for full micronutrient content is very unlikely to occur in the wild especially at up to 60% restriction, yet CR still works at such levels. So why would it work in conditions never found in nature(60% restriction micronutrient fortified food, normal food is unlikely to meet nutrient requirements at such a level of restriction)?

In longer lived species such as some dogs, 25% restriction still yields about 15-18% increase in lifespan. OF course if dogs suffer from the same protein igf1 issue that humans do, it may be that not controlling for protein intake may've reduced some of the benefits, and 25% increase would've been seen.

Regards CR mimetics,
Resveratrol has increased the lifespans of yeast, worms, fruit flies, fish, mice fed a high-calorie diet, genetically induced mitochnodrially dysfunctional mice, and in senescence accelerated SAMP8 and SAMR1 mice. It has also tripled human cell survival to a dose of gamma radiation.

I believe CR can add more than a decade to lifespan, mere lifestyle changes add a decade CR even if it's benefits were modest should at the least match the added lifespan from lifestyle changes.

"Five simple health behaviors promoted by the Seventh-day Adventist Church for more than 100 years (not smoking, eating a plant based diet, eating nuts several times per week, regular exercise and maintaining normal body weight) increase life span up to 10 years."-wikipedia

The fact that resveratrol seems to protect from the adverse effects on lifespan of obesity suggest strong cardiovascular protective effects. While it might not have affected the particular causes of death of normal mice significantly, if it affects other more relevant to human causes of death such as cardiovascular ones it should show better results.

Posted by: Darian S at March 5th, 2014 11:33 AM

@Reason: I read an article recently about a somewhat eccentric seeming billionaire named Peter Nygard and I was curious if you had heard of him. He is proposing to build some kind of clinic in the Bahamas, for stem cell treatments. He has personally been injecting himself with embryonic stem cells for four years -or so he says- and he seeks to create an anti-aging clinic with similar treatments in the Bahamas and in other places. I was not sure what to make of him and was wondering if you had heard of this guy and if so, had an opinion. I searched a bit and found a photo of him chatting with AuBrey DeGrey...but see no evidence of involvement with SENS. What is factual is that he has a sizable amount of personal wealth. Just curious.

Posted by: Jersey Jones at March 5th, 2014 1:27 PM

I believe Dr. Venter was on the panel for the denialist submissions in Technology Review. You would think a person like this who was aware of the concept and even judged it (the SENS approach) they would be less inclined for this slowing aging nonsense.

(yes he was!)

Posted by: Michael at March 5th, 2014 7:19 PM

By panel I of course mean the judging panel, not a co-author of Estep et al.

Posted by: Michael at March 5th, 2014 7:23 PM

Craig Venter is 67 years old. He has no choice but to take these shots. Hopefully he and others succeed in slowing or halting the aging process. I'm cheering for them.

Posted by: johnathan at March 6th, 2014 12:07 AM

It is a pity that Venter will probably wind up wasting all those research dollars on an approach unlikely to work. But sometimes failure is the only way to build a consensus on what does and doesn't work. So in way this investment is helping the research community to 'fail faster' and eventually come around to seriously trying the SENS approach.

I also think the current rush of investment in Calico and now Human Longevity is due to the ever falling costs of genetic sequencing technology. This is a fantastic tool for many things, but when you are a hammer everything starts to look like a nail. Looking for metabolism modifying genes is probably the wrong approach, but it is getting cheaper, so there will be more attempts and failure over the next decade...

Posted by: Jim at March 6th, 2014 4:38 AM

Yes, Craig Venter belonged to the jury of the SENS Challenge back in 2006, the evaluation project initiated by Technology Review magazine, and in the end he wasn't totally against the whole SENS approach but was not really convinced of it, like the other judges too:

"Craig Venter most succinctly expressed the prevailing opinion. He wrote, "Estep et al. in my view have not demonstrated that SENS is unworthy of discussion, but the proponents of SENS have not made a compelling case for it." "

So, if no one has deeper informations that he has changed his fundamental opinion in the last eight years about SENS one cannot expect really that Human Longevity Inc. will incorporate it.

Posted by: Lothar at March 6th, 2014 3:48 PM
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