No, We Cannot (Yet?) Reverse Aging
On hope, hype, and the nuanced truth in longevity research
Russian roulette
As some of you may know, I’ve been keeping an eye on ‘aging research’ for a while now. Exhibit A. I’ve even been invited to talk about it a few weeks ago.
And recently, I’ve seen a lot of headlines along the lines of ‘Growing younger: Radical insights into aging could help us reverse it’ and ‘Skin cells made 30 years younger with new 'rejuvenation' technique‘. (30 years compared to what? We don’t have biological clocks that are that accurate yet.)
Now, I’m all for a tasty headline or two, yet I’d like to inject some healthy skepticism into the promises implied by said headlines. I did so in a Twitter thread earlier this month, but sometimes more characters can be helpful. (If you are on Twitter and aren’t following me, what are you doing with your life? I’m kidding, of course. But do say hi if you feel like it.)
My key points:
In lab animals and cell cultures, in very tightly controlled conditions, yes, scientists can extend healthy lifespan and (partially) reprogram tissues to what looks like a younger state. But compared to what? In Thinking Ahead’s April 2022 Nuggets, I included a tweet by Matt Kaeberlein (an aging expert) who rightfully pointed out that the characteristics of the control group will be very important for the lifespan comparisons. If you compare your experimental mice to a short-lived strain, have you really extended lifespan?
In humans, in the real world, lifespan extension is a very different matter. Sure, there are things we can do to promote health for as long as possible (don’t smoke, exercise, be mindful about food, etc.), but it seems unlikely that these interventions can drastically extend human lifespan beyond the centenarian realm (for the difference between lifespan and life expectancy, see exhibit A).
And that’s not even close to rejuvenation. The new hope/hype on the longevity extension block is epigenetic reprogramming and, despite the skepticism in the previous points, I think it has great potential.
It also still has a lot of problems. For most of these epigenetic tags (molecules that attach themselves to DNA sequences and alter their expression), we don’t know what they do at the tissue/organism level, we don’t know which tags actually matter, and for all the epigenetic clocks based on these tag patterns, we don’t truly know how closely they track biological age, lifespan potential, etc. We need more epigenetic epistemology!
Of course, perhaps we don’t need to know everything to make it work. If a certain treatment can make lab animals/cell cultures look and act younger and live longer, that’s a great start, isn’t it? Yes, but not everything in those models translates to humans, and even in mice, for example, treatments that extend healthy life in one strain shorten it in another. For now, lab animal rejuvenation is Russian roulette.
The proof, as they say, is in the pudding. We still don’t have a recipe.
Buds of hope
But don’t let my inner curmudgeon fool you. I think that research into the biology of aging is crucially important, and am happy to see that it’s attracting funding and attention. All age-related diseases, after all, have one thing in common: advanced age. If we can ameliorate its effects, the gains in terms of healthcare burden and quality of life will be immense.
To get a good sense of where the field actually is, check out this interview with Morgan Levine, who recently joined Jeff Bezos’s massive aging research initiative Altos Labs as principal investigator.
Some quotes that I particularly like:
"There is no standard, agreed-upon way yet for measuring biological age... and there’s probably no “perfect” way either."
People who tend to age slower don’t smoke, don’t really drink, exercise regularly, eat lots of plants, get better sleep, and experience less stress.
On calorie restriction:
"...whether it is down to the restriction of calories or just the lack of overeating, we don’t know. There is also a question about whether the benefit would be maintained over the long term."
Why you should move your body:
"If you bottled the effect of exercise and sold it as a pill, it would be one of the best anti-ageing interventions on the market. And it is never too late!"
And before you run off to buy much-hyped supplements:
"I would caution those interested in self-experimentation not to put too much faith in every single metric. While hypothetically in the future we could have these applications, we aren’t there yet. "
Perhaps there is hope in the hype. Let’s allow it to bud.