Epigenetic Antiaging Progress in Mice Studies

Epigenetic modification has been used to create antiaging effects in mice. Long-term partial reprogramming leads to rejuvenating effects in different tissues of mice and at the organismal level. In addition, they show that the duration of the treatment determined the extent of the beneficial effects.

Cellular rejuvenation therapy safely reverses signs of aging in mice. Salk researchers treated mice with anti-aging regimen beginning in middle age and found no increase in cancer or other health problems later on.

When the researchers looked at normal signs of aging in the animals that had undergone the treatment, they found that the mice, in many ways, resembled younger animals. In both the kidneys and 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 scars—older animals usually show less skin cell proliferation and more scarring. Moreover, metabolic molecules in the blood of treated animals did not show normal age-related changes.

Adding a mixture of four reprogramming molecules (Oct4, Sox2, Klf4 and c-Myc) aka “Yamanaka factors” to cells can reset epigenetic marks to their original patterns.

In 2016, Izpisua Belmonte’s lab reported for the first time that they could use the Yamanaka factors to counter the signs of aging and increase life span in mice with a premature aging disease. More recently, the team found that, even in young mice, the Yamanaka factors can accelerate muscle regeneration. Following these initial observations, other scientists have used the same approach to improve the function of other tissues like the heart, brain and optic nerve, which is involved in vision.

The latest work was long-term partial reprogramming regimens in healthy animals, including different onset timings, during physiological aging.

One group of mice received regular doses of the Yamanaka factors from the time they were 15 months old until 22 months, approximately equivalent to age 50 through 70 in humans. Another group was treated from 12 through 22 months, approximately age 35 to 70 in humans. And a third group was treated for just one month at age 25 months, similar to age 80 in humans.

Compared to control animals, there were no blood cell alterations or neurological changes in the mice that had received the Yamanaka factors. Moreover, the team found no cancers in any of the groups of animals.

Youthfulness effects were seen in the animals with longer seven or 10 months treatments but not the animals treated for just one month. The treated animals were analyzed midway through their treatment and the effects were not yet as evident. Partial reprogramming protocols can be designed to be safe and effective in preventing age-related physiological changes.

Nature Aging : “In vivo partial reprogramming alters age-associated molecular changes during physiological aging in mice.”

Partial reprogramming by expression of reprogramming factors (Oct4, Sox2, Klf4 and c-Myc) for short periods of time restores a youthful epigenetic signature to aging cells and extends the life span of a premature aging mouse model. However, the effects of longer-term partial reprogramming in physiologically aging wild-type mice are unknown. Here, Genetech and Salk Institute researchers performed various long-term partial reprogramming regimens, including different onset timings, during physiological aging. Long-term partial reprogramming lead to rejuvenating effects in different tissues, such as the kidney and skin, and at the organismal level; duration of the treatment determined the extent of the beneficial effects. The rejuvenating effects were associated with a reversion of the epigenetic clock and metabolic and transcriptomic changes, including reduced expression of genes involved in the inflammation, senescence and stress response pathways. Overall, our observations indicate that partial reprogramming protocols can be designed to be safe and effective in preventing age-related physiological changes. They further conclude that longer-term partial reprogramming regimens are more effective in delaying aging phenotypes than short-term reprogramming.

SOURCES – Nature Aging, Salk Institute
Written by Brian Wang, Nextbigfuture.com