Age may be just a number, but it is also a number that often has unwanted effects, from brittle bones and weaker muscles to increased cardiovascular disease and cancer. Now, scientists at the Salk Institute, in collaboration with Genentech, a member of the Roche group, have demonstrated that they can safely and effectively reverse the aging process in middle-aged and elderly mice by partially resetting their cells to younger states.
The method, according to a co-author, is effective in mice, and safe and effective, according to the Roger Guillemin Chair. This approach may, in addition to restoring tissue and organismal health by improving cell function and resilience in different disease situations, such as neurodegenerative diseases.
As organisms age, it is not just their appearance and health that progress; every cell in their bodies carries a molecular clock that records the passage of time. Unlike younger individuals or animals, organisms with four reprogramming moleculesOct4, Sox2, Klf4 and cMyc, also known as Yamanaka factorsto, may reverse these epigenetic markings to their original patterns. This technique is used to measure adult cells, developmentally speaking, into stem cells.
For the first time, the Izpisua Belmontes lab informed that they might utilize the Yamanaka factors to counteract signs of aging and increase life spanin mice with a premature aging disease. More recently, the lab found that the Yamanaka factors can accelerate muscle regeneration. Other researchers have used the same approach to improve the function of other tissues, such as the heart, the brain, and the optic nerve.
Izpisua Belmonte and his colleagues used Yamanaka factors to evaluate variations in healthy animals from the time they were 15 months old until 22 months, according to the group''s average age of 50 to 70 in humans. Another group was then treated for one month at age 25 months, similar to age 80 in humans.
Pradeep Reddy, a Salk staff scientist and co-first author of the new book, stated that using this approach for a longer time period was effective. In fact, we did not notice any detrimental effects on these animals'' health, behavior, or body weight.
There were no blood cell abnormalities or neurological abnormalities in mice that had received Yamanaka factors, according to the study. Achieved no cancers in any of the animals'' groups
The researchers examined the normal signs of age in animals who had been treated. Both the kidneys and the skin, the epigenetics of treated animals more closely resembled epigenetic patterns seen in younger animals. When injured, the skin cells of treated animals had a greater ability to proliferate and were less likely to form permanent scarsolder animals. Moreover, metabolic molecules in the blood of treated animals did not show normal age-related changes.
This youthfulness was observed in the animals treated for seven or ten months with the Yamanaka factors, but not the animals treated for one month. Whats more, when the treated animals were analyzed midway through their treatment, the effects were not yet as evident. This suggests that the therapy is not only causing longevity, but also driving it backwards. However, more research is required to distinguish between the two.
The team is planning future research to help analyze how specific molecules and genes are affected by long-term treatment with the Yamanaka factors. They are also developing new approaches of delivering the factors.
We want to restore resilience and function to older cells so they are more resistant to stress, injury, and disease. This study indicates that, at least in mice, there is a path forward to accomplishing that.