New Approach to Reverse Aging and Restore Cellular Function

Researchers have opened a new front in the battle against aging and diseases associated with old age through a ground-breaking study. The research was carried out by a group of experts at Harvard Medical School, and it has shown the first chemical method to train cells to be in a younger condition. This was previously only possible with a potent gene treatment.

Chemical Approach to Reverse Aging and Restore Cellular Function
Mice in the Sinclair lab have been engineered to age rapidly to test the effectiveness of therapies to reverse the aging process. The mouse on the right has been aged to 150% that of its sibling on the left by disrupting its epigenome. Image Credit: D. Sinclair, Harvard Medical School

On July 12th, 2023, researchers from Harvard Medical School, the University of Maine, and the Massachusetts Institute of Technology (MIT) published a new priority study in the journal Aging.

The authors are Jae-Hyun Yang, Christopher A. Petty, Thomas Dixon-McDougall, Maria Vina Lopez, Alexander Tyshkovskiy, Sun Maybury-Lewis, Xiao Tian, Nabilah Ibrahim, Zhili Chen, Patrick T. Griffin, Matthew Arnold, Jien Li, Oswaldo A. Martinez, Alexander Behn, Ryan Rogers-Hammond, Suzanne Angeli, Vadim N. Gladyshev, and David A. Sinclair.

The research team’s results add to the knowledge that adult cells could become induced pluripotent stem cells (iPSCs) by expressing particular genes known as Yamanaka factors. This Nobel Prize-winning finding made others wonder if it could be possible to slow down biological aging without making cells excessively young and susceptible to cancer.

The goal of this new study was to identify molecules that, when combined, could regenerate human cells and reverse cellular aging. They created real-time nucleocytoplasmic protein compartmentalization (NCC) assays and transcription-based aging clocks as high-throughput cell-based assays to distinguish between young and senescent cells.

The team has made the amazing finding of identifying six chemical cocktails that reverse transcriptome age and return NCC and genome-wide transcript profiles to youthful states in less than a week.

By virally delivering particular Yamanaka genes into cells, Harvard researchers previously showed that it is possible to reverse cellular aging without unchecked cell proliferation.

Promising findings have been found in research on the optic nerve, brain tissue, kidney, and muscle. Enhanced vision and an extended lifespan have been seen in mice, and more recently, enhanced vision in monkeys has been reported.

This discovery has far-reaching consequences, potentially leading to whole-body regeneration and regenerative medicine. This breakthrough could change the treatment of aging, accidents, and age-related disorders by creating a chemical alternative to age reversal via gene therapy.

It also provides the possibility of reduced prices and quicker development times. The lab's age reversal gene therapy is currently undergoing preparations for human clinical trials in the wake of successful results in reversing blindness in monkeys in April 2023.

Until recently, the best we could do was slow aging. New discoveries suggest we can now reverse it. This process has previously required gene therapy, limiting its widespread use.

David A. Sinclair, A.O., Ph.D., Professor, Department of Genetics, Harvard Medical School

Sinclair is also the co-Director of the Paul F. Glenn Center for Biology of Aging Research.

The Harvard team is looking forward to a time when age-related diseases can be properly treated, injuries can be mended more quickly, and the possibility of whole-body regeneration is a reality.

Sinclair concluded, “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.

Source:
Journal reference:

Yang, J.-H., et al. (2023). Chemically induced reprogramming to reverse cellular aging. Aging. doi.org/10.18632/aging.204896

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