How can we reverse aging?
EXTENDING HUMAN LIFESPAN AND AGE REVERSAL - WITH JAN VIJG
Rejuvenation and regeneration, hope versus hyperbole, healthspans and lifespans. Such is the frenzied focus on the potential for new drugs to extend our life expectancy right now, I cannot deliver a keynote on the future of healthcare or even the future of the world in general without addressing the possibility of ‘age reversal’ therapies.
But it’s a complex field, with more than a few charlatans and opportunists promising new drugs that’ll buy you 150 years and more, and a lot of giddy investors pumping big dollars into it — witness Altos Labs breaking cover earlier this year as the most cashed-up start-up in history, the billions to be set aside for geroscience by Saudi Arabia, and so on. All of which makes sifting the rhetoric for the reality extra challenging!
So I visited the Albert Einstein College of Medicine in New York City and asked one of the world’s leading geroscientists to help me better understand aging processes.
MEETING JAN VIJG
Jan Vijg is Professor and Chairman of the Department of Genetics at Albert Einstein College of Medicine and offers one of the most accomplished voices on the subject. When he comments publicly, he does his utmost to stay grounded in the science and the data. The perfect person to cut through to the reality!
He was exceptionally generous in taking time out of his busy schedule to walk me through the complexities of his field. As you will hear, I also discovered he had a wicked sense of humor and shared a lifelong curiosity about broader trajectories in innovation.
It was a wonderful, brain-expanding conversation and we canvassed nothing less than tinkering with the future of our species biological age. Thank you Jan!
CHECK OUT THE PODCAST TRANSCRIPT →
THE “REJUVENATION” GOAL
Having listened to Jan, isn’t it interesting how quickly we start hitting obstacles to human “rejuvenation” therapies? I opened with what I thought would be a relatively straightforward question: whether we were close to scientific consensus on causes of aging at the cellular level.
How much is down to altered aging of the genome and how much altered epigenome? We don’t know exactly. Have we identified every factor, or are we still missing important parts of the picture? Most likely the latter.
So here is challenge #1: if we don’t have one cause of aging, but multiple causes, then where to start? And from a purely logical point of view, if we don’t know the causes precisely, then how to mix a ‘single cocktail’ or ‘an endless drug cocktail’ – to borrow two of Jan’s wonderful phrases – for partially reprogramming somatic cells?
EVOLUTIONARY BASIS OF LIFESPAN
Next challenge: the evolutionary basis of human lifespan. Is there a natural limit arrived at via evolution or, as some people argue, is there no limit and can we theoretically – via careful avoidance/manipulation/reversal of aging and age-inducing factors imposed from the outside – live forever? Jan walked me through the science pointing to a natural limit to live longer, around one hundred and fifteen years.
Not a ‘hard limit’ but a ‘soft limit’ – a biological, even statistical place that the vast majority of us arrive at when our aging cells are no longer in a good enough shape to keep us going – but still a limit. This again implies a great challenge in turning back the clock with therapeutics.
The research paper he mentioned during our conversation, by the way, is “Why Gilgamesh failed: the mechanistic basis of the limits to human lifespan” published in Nature Aging and provides an excellent overview of his arguments.
COMPLEXITIES ON COMPLEXITIES
And as Jan explained, it gets worse. If you think all DNA sequences perform the same simple, easy-to-define roles from birth to death then think again. DNA sequences that serve an important survival purpose early in life might produce detrimental or even fatal outcomes (such as heart disease) later on because they were ‘baked’ by evolution in a period when externalities such as trauma and disease killed most of us before we reached thirty.
So how do you attack such a sequence with a therapy, and more importantly when do you attack it? And what if efficacy depends on attacking it early, or indeed at the very beginning of a human life? Do we edit embryos He Jiankui style and, in which case, who gives the OK on that? The parents?
Oh, and if the developed transgenic DNA repair therapies should prove the most promising pathway to rejuvenation, then how far do you “rollback” the changes? Mutations are essential to the species. They define “us” as individuals. How much to undo before you lose more than you gain?
Tough questions!
AN OPEN MIND
Note how Jan made clear he does NOT consider interventions that fundamentally extend lifespan impossible, just mind-bendingly complex, and much more complex than some of the “boosters” out there would have us believe.
He monitors all of his colleagues work and endeavors to stay grounded in real science and real experimental data at all times. He keeps an open mind. We should do the same. But wow, what a challenge!
TARGET: HEALTHSPAN
All of which led our discussion back to extending “healthspan” as a far more realistic target for the near future. Here we are talking about extending cellular health and thus our chances of living to the natural limits of our lifespans – i.e. increasing average rather than maximum lifespans. Here there IS room for optimism. Studies show we can be hopeful of therapies where targeted partial reprogramming of specific cells in specific organs like stem cells to restore youthful function and resistance to disease.
I see a cross-over here with those aspects of regenerative medicine where we are learning to make human organ repairs using cells as ‘building blocks,’ such as I observed in Anthony Atala’s lab on my visit to the Wake Forest Institute For Regenerative Medicine. One field, I expect, will inform the other.
GAME-CHANGING THERAPIES
In my view, and after listening to Jan, I expect to see a series of “point therapies” announced by laboratories in the next decade. Think restoration of age-related hearing loss, specific skin conditions, male pattern baldness. All big targets. Add another decade or so to navigate all the trials and FDA approvals and some will translate into general availability, at prices determined by what the market will bear … and eye-wateringly lucrative returns.
Although we cannot rule out therapies that break the limits to human lifespan (and I’ll go further and say it is probable—eventually) let’s keep it real: the sheer scale of the challenge of achieving the desired outcomes while avoiding detrimental effects pushes my personal timetable beyond 2050, which is to say, well into ‘haven’t got a clue’ territory. Like everyone else, I’ll keep watching and learning.
And if and when those lifespan-extending therapies do come, I envision a rollout like this: early recipients will score an extra few years, then five, then more again, with each incremental step also surfacing (because of the hideous complexities) new and unforeseen problems, each of which will also represent a new and potentially worse pathway to death. We will speak of early recipients not so much as ‘the lucky few’ as ‘the brave pioneers.’
REWRITING THE FUTURE OF HEALTHCARE
Even after the hyperbole is stripped away, what remains is an exceptionally exciting frontier. What’s possible now is light years ahead of what anybody would have predicted ten years ago. Our genomic toolsets are comprehensive enough to edit life in any way we want. The limits lie not in the edits, but in our understanding of the multitude of switches and roles and pathways and outcomes: complexities on complexities.
Jan and all his colleagues are going to be super-busy and – despite all his tongue-in-cheek protestations – well-funded through the decades ahead. And for good reasons. Healthspan therapies are set to improve the lives of millions, rewrite our expectations and demands of healthcare systems, and transform our understanding of ‘the aging experience.’
Not immortality, to be sure, but revolutionary. Shoot for the stars, as they say, and you might come back with a handful of moondust.