▎ WuXi AppTec content team editor
Aging never gives warning, but quietly comes, it usually appears when you are most defenseless, when you look in the mirror, you accidentally find that there are wrinkles in the corners of your eyes, one or two white hairs in your hair, or a small wound that takes a long time to heal, then you realize that your body really begins to grow old.
But the question we want to know more is, how to slow down aging, or even whether it is possible to reverse it? In 2016, scientists at the Salk Institute of Biology made a preliminary attempt to address this problem, when their study published in Cell showed that by modulating the expression of "mountain factors," cells could be induced to become younger and signs of aging were significantly reduced.
▲ After treatment, the recovery of damaged muscle cells becomes stronger (from left to right) (Image source: References[2], credit: Salk Institute)
The "Yamanaka factor" used here is the Oct4, Sox2, Klf4, and cMyc discovered by Nobel laureate Shinya Yamanaka, four factors that have the ability to reprogram cells. With age, the genes carried by cells will continue to increase the molecular markers associated with time, so the epigenetic patterns of senescent cells and young cells are different, and what Yamanaka factor does is to reverse the aging pattern into a young pattern, indirectly helping a weight to rejuvenate.
In addition to in vitro experiments, the 2016 "Cell" study was also tested in progeria mice and found that briefly promoting factor expression in the mountains could extend the lifespan of these mice by 30%.
In the latest "Nature- Aging" paper, researchers at the Salk Institute of Biology once again pushed this direction forward, they tried to use the Yamanaka factor therapy in healthy aging mice, the mice were divided into two groups according to age, one group was treated at about 15 months, and the course of treatment was up to 7 months (equivalent to 50-70 years old in humans). Another group of mice started treatment for 10 months (equivalent to a human age of 35-70 years) from 12 months of age.
Professor Juan Belmonte and Dr Pradeep Reddy, leaders of both studies (Credit: References[1], credit: Salk Institute)
During the treatment that lasted for several months, the researchers did not observe blood cell abnormalities or neurological changes in the experimental mice, and most importantly, regular and reasonable scheduling of Yamanaka factor therapy would not cause serious side effects of tumors in mice.
After treatment, the researchers observed few conventional signs of aging, such as the kidneys and skin of the mice, in senescent mice, where epigenetic patterns were very similar to those of young mice, whose skin recovered faster than untreated mice after damage and left little permanent scarring. The metabolic molecules in the blood are basically not in a state of aging at all, showing a pattern of youth, that is, it is difficult to distinguish these mice by blood tests alone.
Reprogramming from the cellular level can reverse aging in individuals (Image source: Reference[1], credit: Salk Institute)
Whether it is 7 months or 10 months of treatment, the benefits of rejuvenation can be obtained after treatment. However, some mice that were treated for only 1 month did not change significantly, and even in mice treated for 10 months, the rejuvenation effect was not very obvious at halfway through the treatment. This suggests that the mechanism of factor therapy in the mountains is not to pause aging, but to turn the clock of aging back, and when the reprogrammed young cells prevail, the overall aging characteristics of mice will weaken.
Of course, the use of mountain factors to regulate epigenetics is a very delicate process, in the past observations of the research team, if the use of mountain factors for a period of time (such as 7 consecutive days) of high frequency (such as 7 consecutive days), mice may die, only the frequency is reduced to 2 days of treatment, 5 days interval can really achieve the effect of reversing aging.
It is also based on these results that the progress of relevant clinical trials still needs to wait a certain amount of time, "we really want to know under what conditions this way is safe for long-term use," said study co-author Dr. Pradeep Reddy, "the mice in the new study did not show significant side effects," which is a good sign."
Reversing aging and allowing senescent cells to regain resilience and function is the first step in solving the problem of aging, at least we have witnessed it in mice now, so how far away is it from humans?
Resources:
[1] Cellular rejuvenation therapy safely reverses signs of aging in mice. Retrieved Mar 7th, 2022 from https://www.eurekalert.org/news-releases/945240
[2] Turning back time: salk scientists reverse signs of aging. Retrieved Mar 7th, 2022 from https://www.salk.edu/news-release/turning-back-time-salk-scientists-reverse-signs-aging/
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