Science Gazette

In mice, cellular rejuvenation treatment safely reverses aging symptoms

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Researchers gave mice an anti-aging treatment while they were in their middle years and observed no rise in cancer or other health issues later on.

Although age is simply a number, it has a lot of negative consequences, such as brittle bones and weak muscles, as well as an increased risk of cardiovascular disease and cancer. Scientists at the Salk Institute have now shown that they can safely and efficiently reverse the aging process in middle-aged and old mice by partly resetting their cells to more youthful states in partnership with Genentech, a Roche group company.

“We are ecstatic that we can apply this strategy to halt aging in normal animals throughout their lives. In mice, the approach is both safe and effective “Juan Carlos Izpisua Belmonte, a professor at Salk’s Gene Expression Laboratory and co-corresponding author, agrees. “This technique may give the biomedical community with a new tool to restore tissue and organismal health by enhancing cell function and resilience in diverse illness circumstances, such as neurodegenerative disorders, in addition to combating age-related diseases.”

Not alone do creatures’ outer looks and health change as they age; each cell in their body has a molecular clock that tracks the passage of time. In comparison to younger individuals or animals, cells separated from older humans or animals exhibit distinct patterns of chemicals throughout their DNA, known as epigenetic markers. Scientists have discovered that injecting a cocktail of four reprogramming molecules into cells — Oct4, Sox2, Klf4, and cMyc, often known as “Yamanaka factors” — may restore epigenetic patterns. This method allows researchers to turn adult cells into stem cells at a later stage of development.

In 2016, Izpisua Belmonte’s group demonstrated for the first time that the Yamanaka factors may be used to slow down the symptoms of aging and extend the lifespan of mice with a premature aging condition. The scientists recently discovered that Yamanaka factors may speed up muscle regeneration in young mice. Other scientists have utilized the same strategy to enhance the function of other organs such as the heart, brain, and optic nerve, which is crucial in vision, as a result of these first findings.

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Izpisua Belmonte and his colleagues examined several approaches to cellular rejuvenation in healthy mice as they aged in the latest research. One group of mice was given Yamanaka factors on a regular basis from the time they were 15 months old until they were 22 months old, which is about equal to human ages 50 to 70. Another group was treated for 12 to 22 months, or 35 to 70 years in human years. A third group was given treatment for only one month at the age of 25 months, which is equivalent to the human age of 80.

“What we really wanted to prove was that employing this strategy over a longer period of time is safe,” says Pradeep Reddy, a Salk staff scientist and co-first author of the new research. “In fact, we found no detrimental consequences on these animals’ health, behavior, or body weight.”

There were no blood cell abnormalities or neurological changes in the Yamanaka factor-treated mice as compared to control mice. Furthermore, no malignancies were discovered in any of the animal categories.

When the researchers examined typical markers of aging in the mice that had received the medication, they discovered that the mice resembled younger animals in many respects. The epigenetics of treated animals were more similar to epigenetic patterns found in younger animals in both the kidneys and the skin. When treated mice were damaged, their skin cells had a stronger capacity to multiply and were less likely to develop permanent scars, while older animals had less skin cell proliferation and more scarring. Furthermore, metabolic components in the blood of treated mice showed no signs of normal aging.

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This youthfulness was detected in mice treated with Yamanaka factors for seven or ten months, but not in animals treated for only one month. Furthermore, the effects of the therapy were not yet apparent when the animals were evaluated halfway through their treatment. This shows that the therapy isn’t only delaying aging, but actually reversing it, but additional study is required to make the distinction.

The team is currently working on a study to see how long-term therapy with the Yamanaka factors affects individual molecules and genes. They’re also coming up with innovative methods to convey the variables.

“At the end of the day,” adds Reddy, “we want to restore resilience and function to older cells so they are more resistant to stress, damage, and illness.” “This research suggests that, at least in mice, there is a way to get there.”

In addition to being a professor at the Salk Institute, Belmonte is an Institute Director at Altos Labs, Inc.

Mako Yamamoto, Isabel Guillen Guillen, Sanjeeb Sahu, Chao Wang, Yosu Luque, Javier Prieto, Lei Shi, Kensaku Shojima, Tomoaki Hishida, Concepcion Rodriguez Esteban, and Concepcion Rodriguez Esteban of Salk; Kristen Browder, Zijuan Lai, Qingling Li, Feroza Choudhury, Weng Wong, Yuxin Liang,

The Universidad Católica San Antonio de Murcia (UCAM) and Fundación Dr. Pedro Guillén collaborated on the research.

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