PUMPING IRONY: Forever Young?

Let’s just imagine, for the sake of argument, that you’re trudging through your late 60s, feeling mostly OK but not always that great. You’re taking something to tamp down your cholesterol levels and something else for your blood pressure, and your doctor says you’re on a path that will eventually meet up with type 2 diabetes. Meanwhile, occasional memory lapses suggest dementia may be lurking around the corner.

These are not matters that regularly occupy your mind, but while channel surfing some night you land on a commercial promoting a pill that will magically make you 10 YEARS YOUNGER! You are naturally skeptical, but you mention the drug to your doctor during your next appointment, and you find yourself headed to the pharmacy later that day with a prescription in hand and your eyes fixed on a surprisingly long and healthy future.

This is a scenario Harvard scientist David Sinclair, PhD, envisions sometime in the coming years. And he believes the results of research released earlier this month in the journal Cell bring us all a bit closer to a time when we’ll be able to roll back the years pharmaceutically. “We think the various causes of aging may be addressable with a single treatment to reset the cell,” he tells the Boston Globe. “So, in the future, we could get one treatment — it could be a pill, it could be an injection — to go back 10 years [in cellular life], and then we’ll repeat that process every 10 years.”

The 13-year study, involving Sinclair’s Harvard lab and 18 others, describes how researchers damaged the DNA of lab mice to replicate the age-related breaks of DNA in human cells. The mice quickly showed the effects of aging before a three-gene treatment reversed the forced epigenetic shifts and restored their youthful vigor.

Sinclair and his team admit they can’t completely explain how or why their genetic manipulation managed to hasten — and then reverse — aging in the mice, but they suspect it has something to do with activating a spare copy of epigenetic software that was able to reprogram the cells.

“It is now apparent that mammals retain a backup copy of youthful epigenetic information that can safely restore the function of old tissues, akin to reinstalling software,” the study authors note in Cell.

On a certain level, there’s a lot to like about the notion that we all come equipped with a fresh set of cellular software programmed to reinvigorate our aging genes. But I have to agree with Thomas Rando that rebooting a computer is a little less daunting than reconfiguring our DNA.

Rando, MD, PhD, director of UCLA’s Broad Stem Cell Research Center, lauds the researchers’ innovative portrayal of the aging process, but he reminds us that mice are not humans and that messing in the cellular world could trigger dysregulated cell growth and cancer. “That’s the biggest risk in this whole field of aging reprogramming,” he tells the Globe. “There will always be a safety issue in attempts to reverse aging. There will always be the risk of unwanted outcomes in mucking with the genome.”

That’s not likely to dissuade Sinclair and the growing cadre of antiaging researchers from continuing their pursuit of perpetual youth. Human trials will no doubt proceed at some point, as will lobbying efforts to convince the Food and Drug Administration (FDA) to consider defining aging as a specific disease. Without that classification, all antiaging studies will have to present their results as antidotes to a particular age-related malady, such as Alzheimer’s, rather than as an all-encompassing solution to growing old.

And while the FDA has been known to tweak its criteria for drug approvals (see: Aduhelm), labeling as a disease a condition affecting every human may be a bridge too far for even that Big Pharma–friendly agency. So, it’s certainly premature to engage in much conjecture regarding such variables as demand, pricing, and insurance coverage. We can, however, ponder the potential demographic, economic, and psychological side effects of a popular drug that allows a select portion of the population to extend its lifespan well beyond its current limits.

On the plus side, Ferris Jabr writes in the New York Times, some antiaging experts believe bio-medical interventions to extend lifespans could reduce the toll age-related diseases exact on seniors while allowing them to pursue a variety of fulfilling careers. “Imagine, some say, how wise our future elders could be,” he notes. “Imagine what the world’s most brilliant minds could accomplish with all that time.”

Others are less sanguine, pointing to an already overpopulated planet where socioeconomic — and lifespan — disparities would only worsen should an expensive life-extending drug become a reality. And they suspect an older population would be less amenable to positive cultural change.

Jabr cites comments from Paul Root Wolpe, PhD, director of the Center for Ethics at Emory University, during a 2016 public debate on life extension: “There is a wisdom to the evolutionary process of letting the older generation disappear,” Wolpe argues. “If the World War I generation and World War II generation and perhaps, you know, the Civil War generation were still alive, do you really think that we would have civil rights in this country? Gay marriage?”

And Jabr questions whether we are psychologically suited to the sort of extended lifespan Sinclair and others promote. “All of human culture evolved with the understanding that earthly life is finite and, in the grand scheme, relatively brief,” he writes. “If we are one day born knowing that we can reasonably expect to live 200 years or longer, will our minds easily accommodate this unparalleled scope of life? Or is our neural architecture, which evolved amid the perils of the Pleistocene, inherently unsuited for such vast horizons?”

In their hot pursuit of an extended lifespan, Jabr argues, Sinclair and his ilk may actually be searching for something far more elusive: “not for a life that is simply longer, but for one that is long enough to feel utterly perfect and complete.”

Good luck finding a pill that guarantees that.

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