Longer and better life


in 2006, Shinya Yamanaka, a Japanese researcher in the field of stem cells, has discovered how to reprogram adult cells and return them to an embryonic state. This discovery won him the Nobel Prize. It also revolutionized cell biology and the search for ways to treat human disease.

Researchers are now determined to use cellular reprogramming (or epigenetic reprogramming) to reverse aging and eradicate the diseases associated with it.

“The effects could be broader than those of Crispr,” says biologist David Sinclair, referring to the revolutionary gene-editing technology. […] It’s probably the biggest thing since Crispr in terms of funding and people dedicated to it. »

In early 2022, a group of prominent tech entrepreneurs, including Jeff Bezos (founder of Amazon), revolutionizes the tightly connected world of aging research. They invested $3 billion in reprogramming company Altos Labs. Shinya Yamanaka signed on there as a consultant. Other prominent scientists, in prestigious university positions, were poached.

We can see the huge investment in nascent technology in two ways: the embodiment of Silicon Valley hubris or a smart bet on the medicine of the future.

“People aren’t going to invest big money if the science isn’t credible,” notes Steve Horvath, who recently retired from UCLA to join Altos. So the question is whether everyone will benefit from it. »

Shinya Yamanaka used four transcription factors. These proteins initiate and regulate gene expression. Thanks to them, the researcher erases the identity of the mature cells. In other words, it returns them to their original state.

It was a biologist working on organ regeneration, Juan Carlos Izpisua Belmonte, who gave the idea to apply this method to aging. He wanted to use Yamanaka’s factors to turn back time halfway – to restore the elasticity of young cells, while retaining their identity and function.

Izpisua Belmonte and her team at the Salk Institute for Biological Studies in La Jolla, California, have been experimenting with mice for several years. Without much success. Until they found a protocol that reanimates the animals instead of killing them.

Using partial reprogramming of the cells, they extended the life of premature mice and accelerated the recovery of mice that aged normally but suffered muscle injuries. At the time, Izpisua Belmonte said these experiments showed that aging “may not have to be looked at in one direction.”

Today, Altos’ chief scientific officer, he no longer speaks publicly about the possibility of making aging a two-way street. The company insists it is not looking to reverse aging, but disease.

Supporters may not like the long and questionable history of snake oil to prevent aging from being remembered. Or keep in mind that the Food and Drug Administration will approve treatments for disease, not aging.

What’s the difference? David Sinclair asks, rolling his eyes. A professor of genetics, Sinclair is also co-director of the Paul F. Glenn Center for Research in the Biology of Aging at Harvard Medical School. And he makes no secret of his mission: to confront aging. Including.

He has founded or invested in more than a dozen companies to commercialize longevity technologies and molecules. At age 53, he took metformin and sprinkled his breakfast with resveratrol. “I try at least once the things people talk about,” he says. I’m curious. I like to try. »

Sinclair lifts weights to keep hormone levels high — and posted on Instagram that he does it for his testosterone. He has recently adopted a vegan diet. “It’s not as boring as I thought it would be,” he says. He closely monitors his biological age through InsideTracker, a company he advised to analyze forty-three biomarkers.

He showed me the results at his desk on the computer. C-reactive protein, marker? “I’m a lot shorter than what a 20-year-old would be,” said Sinclair. He sifts through other data and concludes: “I am very far from what we see among young people.”

Later, David Sinclair wanted to reprogram the cells of mice that were losing sight due to old age. A colleague, an ophthalmology researcher, bets that it won’t work. “And you know what?,” Sinclair gloats. “It worked!”

The results were published in Nature in December 2020. Since then, Sinclair has continued her studies. He says the benefits appear to be long-lasting.

At the same time, Sinclair and the researchers in his lab are conducting amazing “Back to the Future”-type experiments. It accelerates the aging of mice, which become more wrinkled and lethargic. Or they accelerate the aging of one organ, or all organs. By revitalizing aging, they hope to learn how to cut it back.

Sinclair targeted the optic nerve because it is one of the first places in the body to age. Cells stop regenerating there soon after birth. Sinclair believes his studies provide a game-changing model for treating spinal cord injuries and disorders of the central nervous system. He explains that if retrograde the cellular age makes it possible to restore sight, why not also make it possible to regenerate the spinal cord or the ability to walk or remember?

Meanwhile, there is a lot we can do to fight aging. Harvard researchers studied data from 123,219 adults in the United States over decades. Bottom line: Five habits that can increase life expectancy by 14 years for women and 12 years for men: good nutrition, regular exercise, not being overweight, not smoking, and not drinking too much.

“If you only do one sport—which I don’t recommend—exercise is the biggest benefit for you,” says Matt Kaeberlin, MD, professor of laboratory medicine and pathology, and director of the university’s Institute for Longevity and Healthy Aging. Washington.


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