Rejuvenation therapies are worth developing before aging is fully understood: Fight Aging! author responds to aging researcher Miller

Rejuvenation therapies are worth developing before aging is fully understood: Fight Aging! author responds to aging researcher Miller

On November 6, the blog’s author, Reason, responded to aging researcher Richard Miller’s criticism of removing senescent cells to extend lifespan. These cells enter a stable state of growth arrest after stress and can sustain inflammation in tissues.

Reason, co-founder of the biotechnology company Repair Biotechnologies, proposes in his response to Miller that suspected causes of aging should be tested by attempting to repair specific forms of damage in the body. Understanding the mechanisms helps avoid costly mistakes, while the results of repair attempts refine our understanding of aging. Reason argues that without the first experiments removing senescent cells, researchers would still be debating their contribution to bodily deterioration:

“In most fields, the fastest way to understand is to build and fail repeatedly, and sometimes to build and succeed.”

Reason interpreted Miller’s criticism as a demand for understanding before action. In an article published on October 27, Miller challenges the search for a single cause of aging and proposes studying what controls its rate. Drugs, diets, and mutations can already produce long-lived mice. Miller proposes comparing young animals that will age at different rates and looking for changes shared across these interventions. He hopes this will identify mechanisms that slow the decline of many bodily functions together.

In a 2018 study, researchers tested the causal role of senescent cells by transplanting them into mice and testing drugs that remove such cells. After transplantation, strength and endurance declined compared with mice given the same cell types without signs of senescence. A combination of dasatinib and quercetin, which can kill some types of senescent cells, reduced this effect. In naturally aged mice, the same combination improved grip strength and endurance. In a separate experiment involving 147 mice, treatment began at 24–27 months of age; median remaining lifespan increased by 36% relative to the control group.

In a program that tests compounds for their ability to extend lifespan in mice, in which Miller participates, fisetin, another candidate for removing senescent cells, did not extend lifespan under the regimens tested. Activity of the p16 gene served as an indirect measure of the accumulation of these cells. In the liver, kidneys, and brain, researchers found no reduction in its activity that could be distinguished from random variation. For subsequent tests, the authors proposed changing how fisetin is administered or using other agents to remove the cells.

Whether the targeted cells were removed, whether tissue function improved, and whether lifespan increased each require a separate measurement. These measurements help determine the next experiment: testing another agent to remove the cells or examining the effects on the body once cell removal has been confirmed.