Can we reverse aging? A bold new approach could reprogram cells

Aging can feel like an unstoppable force. Some researchers believe it may one day be slowed or even paused, thanks to an emerging technique known as cellular reprogramming.

Curiosity has surrounded this approach since a 2016 mouse experiment at the Salk Institute, where progeric rodents (that age more rapidly than normal) lived longer after exposure to four genes that could rewrite cellular aging.

Lucy Xu, a postdoctoral research fellow at Harvard Medical School, has followed these findings closely.

How reprogramming changes aging cells

Every mammalian cell contains DNA. However, the DNA in your heart cells behaves differently than it does in your skin cells because of the epigenome, an outer layer affected by methylation patterns that can turn genes on or off. Over a lifetime, methylation shifts with diet, pollution, exercise, and stress.

Scientists discovered that activating four reprogramming genes, named after Shinya Yamanaka, can strip away large portions of these methyl marks. This can reset cells to an earlier, more flexible state, which can be good or dangerous.

Potential and pitfalls

Animal studies have linked complete reprogramming to teratomas, which are bizarre growths that sprout tissues like teeth and hair in odd places.

In one early mouse experiment by Spanish researchers, “many of the animals died within weeks,” which reveals just how risky total cellular regression can be.

In partial reprogramming, researchers use fewer Yamanaka genes or cycle them briefly to avoid pushing cells back into a stem cell state. This less-extreme version aims to refresh cells while preserving their identity.

Why safety is a concern

“I don’t believe there can be reprogramming. You’re practically telling these cells to become cancer,” said Charles Brenner, a scientist at City of Hope research center in Duarte, California. Creating extra stem-like cells might be a path to fierce cancers. 

To reduce the odds of uncontrolled cell growth, some scientists use a well-known antibiotic to control gene activity. They turn it on briefly, then shut it off. The hope is that this approach rejuvenates tissues without allowing runaway cell division.

Reprogramming cells in aging tissues

Research from Harvard in 2020 showed promise by focusing on eye tissues in older mice. David Sinclair, a Harvard geneticist who worked on the study, used only three of the original four genes – removing the one most associated with tumors.

A biotech company, Life Biosciences, has advanced this strategy by testing partial cell reprogramming on monkeys with eye damage.

The firm plans to apply for permission to do the same in people who have suffered sudden optic nerve strokes, believing the antibiotic-switch method is safer than previous attempts.

A closer look at aging itself

While eye tissues seem like a controlled starting point, some labs also hope to apply partial reprogramming more broadly.

A follow-up project at the Salk Institute used carefully timed reprogramming in mice with extra copies of reprogramming genes. Tumors were less common, and some tissues showed younger biological markers, although lifespans did not increase.

Those results fuel speculation that certain organs, such as the brain, might benefit from partial reprogramming. Investigations at Stanford University tested this approach in mice, aiming to improve brain aging.

The targeted reprogramming boosted newly formed neurons, though the mice had an uptick in inflammation.

Many questions remain

The technique still prompts concerns about long-term effects and who will have access if human trials succeed. Some fear only people with deep pockets may benefit initially. Others wonder if reprogramming might lead to costly or risky treatments that never live up to the hype.

Some scientists remain optimistic. They believe partial reprogramming might transform eye disease care, and later, other age-related problems. They acknowledge that verifying safety is key and that any therapy for aging must pass rigorous testing.

Life Biosciences expects to begin clinical trials in the near future, and will use partial reprogramming to help certain adults who suffer acute optic nerve issues.

Analysts say these initial results will guide future work. If the therapy shows no tumors or unexpected complications, it could open a path for new treatments targeting age-related loss of function.

“I worry about the speed,” Xu said, noting that more questions need answers before the technology expands beyond small clinical studies.

Future of reprogramming cells

No one knows whether these methods will eventually slow or alter aging in humans. Undeterred, investors hope partial reprogramming can become a novel strategy for a range of conditions.

Research continues across universities and startups. Many experts see partial reprogramming as a step forward, as long as scientists can balance rejuvenation with safety.

Others warn that tampering with cellular identity may unleash problems we can’t yet predict. Even so, interest in these trials keeps growing.

The study is published in the journal Nature.

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