Reverse aging cocktail: First “groundbreaking” discovery for chemically reprogramming cells

18 Jul 2023 --- Reversing cellular aging is possible in less than a week and without causing cells to become too young or turn cancerous, new research finds. This was previously only achievable using gene therapy, limiting widespread use. The study unlocks new solutions in fighting against aging and age-related diseases.

“Until recently, the best we could do was slow aging. Discoveries suggest we can now reverse it,” says David A. Sinclair, A.O., Ph.D., professor, 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.

The discovery has “far-reaching” implications for regenerative medicine and potentially “whole-body rejuvenation.”

Conducted by researchers at Harvard Medical School, Moscow State University, University of Maine and Massachusetts Institute of Technology, the study was published in Aging, titled “Chemically induced reprogramming to reverse cellular aging.”

Potential revolutionary applications
The chemical alternative to age reversal might “revolutionize” the treatment of aging, injuries and age-related diseases with possible lower costs and shorter timelines in development.  

“On the heels of positive results in reversing blindness in monkeys in April 2023, preparations for human clinical trials of the lab’s age reversal gene therapy are in progress,” share the researchers.The mouse on the right has been aged to 150% that of its sibling on the left by disrupting its epigenome (Image Credit: Sinclair, Harvard Medical School).

In a previous study, Harvard researchers showed it is possible to reverse cellular aging without uncontrolled cell growth by virally introducing specific Yamanaka genes into cells. These genes are OCT4, SOX2, KLF4 and c-MYC.

How cells age
The Harvard team envisions a future of effective treatments for age-related diseases and injuries and where the dream of whole-body rejuvenation becomes a reality.

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

The theory of aging posits that aging manifests due to a decline in cellular information, specifically epigenetic information. “This triggers a cascade of events, including mitochondrial dysfunction, inflammation and cellular senescence, leading to a progressive decline in cell and tissue function, manifesting as aging and age-related diseases,” reads the study.

“The accumulation of senescent cells with age promotes inflammation and generates additional reactive oxygen species, locally and across the organism, contributing to a broad range of age-related diseases.”

Rejuvenating potions
The research builds on the Nobel Prize-winning discovery of the expression of specific genes, Yamanaka factors, that can convert adult cells into induced self-renewing pluripotent stem cells (iPSCs). Based on this, the scientists questioned whether it would be possible to reverse cellular aging.

Thus, the team screened for molecules that could reverse cellular aging and rejuvenate human cells. 

They then distinguished young cells from old and senescent cells by developing high-throughput cell-based assays, transcription-based aging clocks and a real-time nucleocytoplasmic protein compartmentalization (NCC) assay.

Followingly, the team discovered six chemical cocktails that restore NCC and genome-wide transcript profiles to youthful states and reverse transcriptomic age in less than a week.

“Experiments are in progress to understand the effect of the cocktails on various cell types from young and old individuals,” write the authors.Age reversal of senescent human skin cells by chemical means (Image Credit: Jae-Hyun Yang, Harvard Medical School).

Most potent cocktail
According to the research, the chemical cocktail that induced the most potent rejuvenation was VC6TF. However, the researchers flag that VC6TF has not been reported to be capable of fully reprogramming human cells to chemically iPSCs. 

“All six chemical cocktails, C1-C6, decreased biological and chronological age below that of even the non-senescent cell populations,” write the authors. “Sodium butyrate, a histone deacetylase inhibitor, was one of the most effective additives in both human and mouse cocktails.”

VC6TF consists of five small molecules that play a role in cellular reprogramming. Namely, chemicals valproic acid and CHIR-9902, inhibitors 616452 and tranylcypromine and forskolin, sourced from the Indian Coleus plant.

Within nutrition supplements, forskolin has been touted to help with insomnia and promote weight loss.

Anti-aging solutions
In related news, L’Oréal and Verily jointly launched a multi-year study to help researchers better understand the biological, clinical and environmental factors contributing to skin and hair health over time.

Last week, Shiseido found that the hardening of the stratum corneum, the outermost layer of skin, is a significant cause of wrinkle formation while also developing a treatment for it. 

Researchers at the US National Institutes of Health discovered anti-aging and healing solutions by probing the regenerative properties of Hydractinia symbiolongicarpus, a minute animal living on hermit crabs’ shells.

China-based researchers reviewed the use of natural products containing polyphenols, saponins, alkaloids and polysaccharides as potential anti-aging agents by highlighting the nutrient-sensing pathways these products influence for their health effects.

By Venya Patel