According to research published in science, ten years after Shinya Yamanaka of Kyoto University was awarded the Nobel Prize for discovering a cocktail of proteins that reprogram adult cells into flexible stem cells, two groups have claimed that the proteins might reverse the aging process for whole species or perhaps the human race.
A biotech company used gene therapy to provide Yamanaka factors to aged mice, extending their lives somewhat. Another group used a similar method to repair aging-like alterations in genetically modified mice. In both cases, there is evidence that the Yamanaka factors rejuvenated a section of the epigenome, the suite of chemical changes to DNA and proteins that govern gene expression.
Age reversal claims, according to non-participating physicians, are premature. “These investigations employ reprogramming agents to correct epigenetic alterations that occur throughout aging,” says Matt Kaeberlein of the University of Washington in Seattle. Â
Several studies have indicated that genetically altered mice expressing Yamanaka factors in old age can mitigate some of the consequences of aging. Rejuvenate Bio delivered adeno-associated viruses (AAVs) expressing genes for three OSK components into elderly (124-week-old) mice to investigate a strategy that may be more practical for people. Â
The company revealed in a bioRxiv publication this month that these mice lived an average of 18 weeks, compared to 9 weeks for a control group. They partially restored DNA methylation patterns that were characteristic of younger animals. According to Rejuvenate’s chief scientific officer and co-founder, Noah Davidsohn, gene therapy has been provided to mice with no apparent detrimental side effects.  Â
“It’s provocative—possibly a breakthrough,” says aging scientist Steven Austad of the University of Alabama in Birmingham. This second research, led by Harvard Medical School geneticist David Sinclair, was published in Cell yesterday. For more than two decades, Sinclair has lobbied for various problematic “anti-aging” medications.
Davidson argues that while Sinclair is not participating in Rejuvenate’s study, the two businesses did collaborate on the project’s approach. The “information hypothesis of aging” proposed by Sinclair, which posits that the degradation of our epigenetic markers causes us to age, was tested. He claims that the lifelong DNA repair processes of cells remove these markers.
To put this theory to the test in animals, researchers created a genetically modified mouse that, when given a drug, releases an enzyme that breaks DNA at 20 genomic locations and reliably repairs it. Extensive DNA methylation and gene expression changes verified Sinclair’s idea. The mice became unwell with an epigenetic profile characteristic of aged animals. They began to bald and gray within weeks, and within months, they began to feel frail and saw their tissues age. Â
To investigate if epigenetic degradation might be reversed, the researchers used AAVs expressing OSK genes, which Sinclair’s lab recently proved can correct a visual loss in old rats. The combination reversed many DNA break-induced epigenetic alterations in mice’s muscles, kidneys, and retinas. Sinclair believes the findings indicate epigenome-targeting drugs for human aging and a method to “forward and backward” age an animal. Â
Molecular biologist Wolf Reik, director of the Altos Cambridge Institute of Science (founded last year by rejuvenation company Altos Labs), praised the Harvard team’s sophistication and thoroughness but said the team’s indirect method of inducing epigenetic changes with dramatic DNA breaks that could have other effects makes it difficult to prove those changes cause aging.Â
