Why “reprogramming” is the buzziest approach to reversing aging right now

Earlier this week, Life Biosciences, a biotech company focused on reversing age-related diseases, announced that it had dosed its first volunteer. A person with glaucoma has had an experimental treatment injected straight into their eyeball . The idea is to try to treat the disease—which can cause vision loss—by regenerating healthy nerves in the eye. But David Sinclair, the chairman and cofounder of the company behind the trial, hopes to go further. If the treatment can reverse glaucoma, perhaps similar treatments can reverse other diseases of aging. Maybe, just maybe, they can reverse aging altogether. The approach is designed to work by “reprogramming” cells to a younger state. It’s one of many strategies being explored by biotech companies looking to slow and reverse the process of aging. But of all of them, it seems to be the one that is truly taking off . Aging is complicated. As we get older, we experience so many changes across pretty much all our biological systems. Scientists have tried to categorize these effects. In 2013, one team published a seminal paper describing nine “ hallmarks of aging .” That list features many of the processes scientists have attempted to target. But some of those targets have fallen in and out of fashion over the years. Take telomere attrition, for example. Telomeres are DNA sequences at the ends of our chromosomes, often likened to the plastic caps that stop the ends of our shoelaces from fraying. When cells divide, telomeres shorten until, eventually, the DNA is vulnerable to damage. When I started reporting on aging, telomere shortening was all the rage. Shrinking telomeres had been linked to age-related diseases of the heart and brain. Shortened telomeres were considered a sign of premature aging . In 2017 Liz Parrish, CEO of the biotech company BioViva, injected herself with an experimental gene therapy that she hoped might lengthen her telomeres. Then it suddenly seemed to go out of style. Research continued , but all the excitement within the aging and longevity community seemed to move on to another hallmark. (Parrish also continued with self-experimentation; she calls herself “the most genetically modified person on Earth.”) That hallmark was cellular senescence. This happens when cells stop dividing but don’t die, instead entering a “zombie” state in which they churn out chemicals that can cause harmful inflammation. Senescent cells gradually accumulate in pretty much every organ studied, where they are thought to contribute to age-related damage. Why not just periodically clear them out? When a team of scientists took that approach in mice in 2011 , they found they could delay the onset of age-related conditions like cataracts and hunchback. The treated mice even looked younger. But when scientists at Unity Biotechnology trialed a similar approach in people with osteoarthritis and an age-related eye condition in the late 2010s and early 2020s, the results were disappointing . The company laid off every employee in May last year and has since shuttered entirely. Again, that doesn’t mean senolytic drugs that target “zombie cells” won’t work. But it feels as if many in the field have moved on. These days, the buzz is all about reprogramming . The idea here is to essentially return cells to a young state. It’s based on the Nobel Prize–winning discovery that four genetic factors can turn an adult cell into a stem cell, which can be encouraged to develop into pretty much any other cell type. Some promising studies in mice suggest that this approach might help wind back the clock. It seems to improve tissue healing , restore vision , and even improve learning and memory . Running parallel to all this research are repeated injections of hundreds of millions of dollars in funding. In 2021, my colleague Antonio Regalado reported on the founding of the biotech company Altos Labs to pursue reprogramming for rejuvenation. Altos was funded by the billionaire Yuri Milner—reportedly along with