Aubrey de Grey Comments on the Hallmarks of Aging Paper

The Hallmarks of Aging paper was published earlier this year. It is an outline by a group of noted researchers that divides up degenerative aging into what they believe are its fundamental causes, with extensive references to support their conclusions, and proposes research strategies aimed at building the means to address each of these causes. This is exactly what we want to see more of in the aging research community: deliberate, useful plans that follow the Strategies for Engineered Negligible Senescence (SENS) model of approaching aging.

Read through the Hallmarks of Aging and you'll see that it is essentially a more mild-mannered and conservative restatement of the SENS approach to aging - written after more than ten years of advocacy and publication and persuasion within the scientific community by SENS supporters. To my eyes, the appearance of such things shows that SENS is winning the battle of ideas within the scientific community, and it is only a matter of time before it and similar repair-based efforts aimed at human rejuvenation dominate the field. Rightly so, too, and it can't happen soon enough for my liking. SENS and SENS-like research is the only way we're likely to see meaningful life extension technologies emerge before those of us in middle age now die, so the more of it taking place the better.

Aubrey de Grey, author of the original SENS proposals and now Chief Science Officer of the SENS Research Foundation that funds and guides rejuvenation research programs, is justifiably pleased by the existence of the Hallmarks of Aging. See this editorial in the latest Rejuvenation Research, for example:

A Divide-and-Conquer Assault on Aging: Mainstream at Last

On June 6th, a review appeared concerning the state of aging research and the promising ways forward for the field. So far, so good. But this was not any old review. Here's why: (a) it appeared in Cell, one of the most influential journals in biology; (b) it is huge by Cell's standards - 24 pages, with well over 300 references; (c) all its five authors are exceptionally powerful opinion-formers - senior, hugely accomplished and respected scientists; (d) above all, it presents a dissection of aging into distinct (though inter-connected) processes and recommends a correspondingly multi-pronged ("divide and conquer") approach to intervention.

It will not escape those familiar with SENS that this last feature is not precisely original, and it may arouse some consternation that no reference is made in the paper to that prior work. But do I care? Well, maybe a little - but really, hardly at all. SENS is not about me, nor even about SENS as currently formulated (though a depressing number of commentators in the field persist in presuming that it is). Rather, it is about challenging a profound, entrenched, and insidious dogma that has consumed biogerontology for the past 20 years, and which this new review finally - finally! - challenges (albeit somewhat diplomatically) with far more authority than I could ever muster.


Aging has been shown, over several decades, to consist of a multiplicity of loosely linked processes, implying that robust postponement of age-related ill-health requires a divide-and-conquer approach consisting of a panel of interventions. Because such an approach is really difficult to implement, gerontologists initially adopted a position of such extreme pessimism that all talk of intervention became unfashionable. The discovery of genetic and pharmacological ways to mimic [calorie restriction], after a brief period of confused disbelief, was so seductive as a way to raise the field's profile that it was uncritically embraced as the fulcrum of translational gerontology for 20 years, but finally that particular emperor has been decisively shown to have no biomedically relevant clothes.

The publication of so authoritative a commentary adopting the "paleogerontological" position, that aging is indeed chaotic and complex and intervention will indeed require a panel of therapies, but now combined with evidence-based optimism as to the prospects for implementing such a panel, is a key step in the elevation of translational gerontology to a truly mature field.

In essence, as de Grey points out, work on aging has been following the wrong, slow, expensive, low-yield path for a couple of decades: the path of deciphering the mechanisms of calorie restriction and altering genes and metabolism to slightly slow down aging. This path cannot result in large gains in life expectancy and long-term health, and it cannot result in therapies that will greatly help people who are already old. What use is slowing down the accumulation of the damage of aging if you are already just a little more damage removed from death, and frail and suffering because of it, and the treatment will meaningfully alter none of that? If we want to add decades or more to our healthy life spans before we die, then rejuvenation and repair of damage are what is needed: ways to reverse frailty, remove suffering, and restore youthful function.


You are the man, Aubrey. Don't let the haters bring you down. We believe in you.

Posted by: Nathan Voodoo at September 6th, 2013 9:00 PM

Open access? Huh??? Paying 31.50 bucks is not open access. Or do I miss something???

Posted by: Ragle at September 7th, 2013 10:44 AM

@Ragle: Brain failure on my part. de Grey's commentary is open access, not the Hallmarks of Aging paper. I've altered the post accordingly.

Posted by: Reason at September 7th, 2013 12:47 PM

If anyone's interested, a user at forums has posted a link to the full HoA paper in the thread dedicated to reason's entry.

Posted by: Musli at September 7th, 2013 1:31 PM

This being the link to that thread:

Posted by: Reason at September 7th, 2013 1:39 PM

Oh, holy crap. Thanks Musli. I just found "It." I am going to start reading Hallmarks of Aging right now. Thanks again.

Posted by: Nathan Voodoo at September 7th, 2013 1:59 PM

For what it is worth, I predict that you will accomplish your goal much sooner than you think, and with less funding that you believe you need. There will be a surprise finding in the human liver, I don't know just what it will be, but it is something that is stumbled upon, and it will take you where your are headed, and God speed.

Posted by: Glory Lampert at September 7th, 2013 7:28 PM

@Glory Lampert I think it's cool that you are making such predictions. I hope you are right. While I do think that the liver is crucial to detoxification, rejuvenation, and ultimately survival, I do not think that it will be the critical element. Before I state my prediction to the contrary, I will openly say, I could be very wrong. My personal prediction is that, if aging is reduced to only one system of the body, versus the many processes currently being explored by science, it will be the brain, most specifically the limbic system. If one is to search for hypothalamic overactivation and type in an illness such as CFS, it will demonstrate the great effect that stress has on the brain, how it responds, and what feedback mechanisms fire amiss in such a state. That being said, the brain changes from childhood to adulthood, somewhat proportionately to the propensity for illness. Adults are often do not have the resilience to stress that children do, often due to the increased cognitive function, and the repetitive and intense overanalytical nature that follows more "evolved" ways of thinking. I predict that a reversal could work one of two ways. The first, is that neuroscientists could deduce what causes the brain to change, both internal and external environmental factors, and then, would thus be able to bring the brain of an adult back to the being the brain of a child, without interfering with cognitive processes such as logic and reason. The second scenario would be exploring the stress response in its entirety, and figuring out how to only create the minimal amount of stress for growth and positive adaptation, however, reversing the rest of the process that has been unproductive or biologically unneccessary. Without fail, Glory, I respect your intuitive predicition, and am curious to see the outcome. It doesn't matter who is right in the end, maybe none of us. If we can reverse aging, we all win. Anyone who thinks we are both wrong, please contribute. You may have the idea that inspires someone important who may be reading this.

Posted by: Adam at September 8th, 2013 4:40 PM

SENS6 Conference Coverage

I've noticed a lack of coverage of Aubrey de Grey's big SENS6 conference. I'm hoping videos will be posted on youtube like they were for SENS5.

But here's some conference-related coverage that I found:

Crowd-fund longevity research in mice:

(also on indiegogo, from SENS4: )

Final conference activity, Aubrey de Grey arguing why aging isn't programmed while punting down the river and drinking a beer:

Posted by: Carl at September 8th, 2013 11:47 PM

@Carl: Last time, I produced the videos for SENS5. I offered SENSF to do it again for SENS6, but they decided to hire a professional camera crew from the UK this time. I'm going to ask Ben Zealley when the first videos are going to be uploaded to Youtube.

Posted by: Nicolai Kilian at September 9th, 2013 2:24 PM

It seems that de Grey's comments aren't open access anymore :(

Posted by: Antonio at January 3rd, 2017 8:52 AM

Thanks, Michael :) That link works.

Posted by: Antonio at January 4th, 2017 12:25 AM
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