Scientists Identify Chemical Means to Reverse Cellular Aging

Researchers at Harvard Medical School uncovered six chemical cocktails in mice that may help to fight aging and age-related diseases.

The study, led by Professor David Sinclair and published in the journal Aging, is built upon the previous discovery in mice that adding to molecules two specific genes, called Yamanaka factors, could convert adult cells into induced pluripotent stem cells (iPSCs).

iPSCs are cells that have been reprogrammed back into an embryonic-like pluripotent state and can be used for therapeutic purposes, such as creating new blood free of cancer cells for a leukemia patient or neurons to treat neurological disorders.

This Nobel Prize-winning discovery raised the question of whether it might be possible to reverse cellular aging without causing cells to become too young and turn cancerous.

In their new study, the researchers screened for molecules that could, in combination, reverse cellular aging and rejuvenate human cells. They developed high-throughput cell-based assays to distinguish young cells from old and senescent cells, including transcription-based aging clocks and a real-time nucleocytoplasmic protein compartmentalization (NCC) assay. Deterioration of NCC is one of the most well-conserved physiological hallmarks of aging.

Development of the assays allowed the team to identify six chemical cocktails that restore NCC and genome-wide transcript profiles to youthful states and reverse transcriptomic age in less than a week.

The authors say the findings may revolutionize the treatment of aging, injuries, and age-related diseases and potentially lead to whole-body rejuvenation. Previously, reversing cellular aging was only possible using gene therapy, which is expensive and raises safety concerns associated with introducing genetic material into the body. Therefore, the scientists hope that the new chemical means could lower costs and shorter timelines in development.

"Until recently, the best we could do was slow aging. New discoveries suggest we can now reverse it," says David A. Sinclair, A.O., Ph.D., Professor in the Department of Genetics and co-Director of the Paul F. Glenn Center for Biology of Aging Research at Harvard Medical School and lead scientist on the project. "This process has previously required gene therapy, limiting its widespread use."

The findings are consistent with Sinclair’s "Information Theory of Aging" which proposed that a decline of epigenetic information triggers events, such as inflammation and cellular aging, leading to a progressive decline in cell and tissue function and, as a result, aging and age-related diseases.

However, before initiating human trials, the safety of chemical rejuvenation cocktails has to be tested in mammalian animal models.

Sinclair says: "This new discovery offers the potential to reverse aging with a single pill, with applications ranging from improving eyesight to effectively treating numerous age-related diseases.”