Reprogramming old age
Researchers from the Salk Institute, in collaboration with Genentech, a member of the Roche group, have shown that it is possible to safely and effectively reverse the aging process in middle-aged and older mice by returning their cells to a younger state.
Cells isolated from old animals have different epigenetic markers– patterns of chemicals surrounding DNA–compared to cells of young animals. It is known that the addition of Yamanaki transcription factors to cells (mixtures of four Oct4, Sox2, Klf4 and cMYC proteins capable of turning somatic cells into pluripotent stem cells) can return these epigenetic markers to their original patterns.
In 2016, the laboratory of Juan Carlos Ispisua Belmonte showed for the first time that it is possible to use Yamanaki factors to combat signs of aging and increase the life expectancy of mice with premature aging (progeria). In another study, the team found that even in young mice, Yamanaka factors can accelerate muscle regeneration. Later, other scientists used this approach to improve the function of the heart, brain and optic nerve.
In a new study, Ispisua Belmonte and colleagues evaluated the safety of an epigenetic approach to rejuvenation in healthy animals as they age. One group of mice received regular doses of Yamanaka factors from 15 to 22 months, which is approximately equivalent to the age of a person from 50 to 70 years. The other group was treated for 12 to 22 months, which is approximately 35 to 70 human years. And the third group received therapy for only one month at the age of 25 months, which is similar to the age of 80 in humans.
Compared with control animals, mice treated with Yamanaki factors showed no changes in blood cells or neurological changes. Moreover, the group found no signs of cancer in any of the animal groups.
The mice treated looked a lot like younger animals. In the kidneys and skin, epigenetic markers corresponded to animals of a smaller age. When wounded, the skin cells of these mice had a greater ability to proliferate and were less likely to form scar tissue; older animals usually have less proliferation of skin cells and more pronounced scarring. In addition, metabolic molecules in the blood of animals treated with Yamanaki factors did not show characteristic age-related changes.
This youthfulness was observed in mice after Yamanaki factor therapy for 7 or 10 months, but not in animals treated for just one month. Moreover, the analysis carried out in the middle of treatment showed that at that stage the effect was not yet so obvious. This suggests that the treatment does not just stop aging, but actively reverses it, although additional studies are needed to confirm the results.
The group is currently planning a new study to determine which specific genes and how they change with prolonged treatment with Yamanaki factors. They are also developing new ways to deliver these factors.
Article by K.C.Browder et al. In vivo partial reprogramming alters age-associated molecular changes during physiological aging in mice is published in the journal Nature Aging.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of the Salk Institute: Cellular rejuvenation therapy safely reverses signs of aging in mice.