Researchers Safely Used Cellular Rejuvenation Therapy in Mice

In a recently published study scientists at the Salk Institute, in collaboration with Genentech, a member of the Roche group, have shown that they can safely and effectively reverse the aging process in middle-aged and elderly mice by partially resetting their cells to more youthful states. 

As we age, both our external appearance and health change, with every cell in our bodies carrying a molecular clock that records the passage of time. Cells isolated from older people or animals have different patterns of chemicals along their DNA — called epigenetic markers — compared to younger people or animals.

Researchers know that adding a mixture of four reprogramming molecules, Oct4, Sox2, Klf4 and cMyc, also known as “Yamaka factors,” to cells can reset these epigenetic marks to their original patterns. Using this approach researchers can dial back adult cells into stem cells.

In a previous research by Izpisua Belmonte’s lab, scientists reported for the first time that using the Yamaka factors they could counter the signs of aging and increase the lifespan of mice with a premature aging disease. 

New study results 

In the new study, researchers tested variations of cellular rejuvenation in healthy animals as they aged. The mice were treated as follows:

  • From the time they were 15 months old until 22 months (equivalent to age 50-70 in humans).
  • From 12 to 22 months of age (35-70 in humans).
  • Just for 1 month at 25 months of age (80 in humans). 

The researchers wanted to demonstrate that using their approach for a longer time is safe, and they did not find any negative effects on the health or behavior of the animals. Compared with control animals they found no blood cell alterations or neurological changes, and no cancers in any group were found. 

The team found that the animals treated with the Yamaka factors resembled younger animals. They evaluated the kidneys and skin of the treated animals and their epigenetics closely resembled epigenetic patterns seen in younger animals. Also, when injured their skin had a greater ability to proliferate and were less likely to generate permanent scars, and their blood metabolic molecules did not show normal age-related changes. 

These benefits were observed in the animals treated for severe or 10 months with the Yamanaka factors, and not in the animals treated for 1 month only. 

The team is planning to do more studies to evaluate specific molecules and genes, and how they change by long-term treatment with the factors. 


Salk Institute. “Cellular rejuvenation therapy safely reverses signs of aging in mice: Researchers treated mice with anti-aging regimen beginning in middle age and found no increase in cancer or other health problems later on.” ScienceDaily. ScienceDaily, 7 March 2022. <>.

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