Old neurons can block neurogenesis in mice (A senolytic can unblock)

Medical Xpress / Stem Cell Reports / Cell Press ^ | Jan. 20, 2022 | David R. Kaplan et al

[ConservativeMind]

Destroying senescent cells in the aging stem cell niche enhances hippocampal neurogenesis and cognitive function in mice, researchers report.

"Our results provide further support for the notion that excessive senescence is a driving factor behind aging, and even late-life reduction of these cells can rejuvenate and restore the function of the stem cell niche," says senior author David Kaplan. "Moreover, they identify stem cells as a key cellular target, potentially explaining the widespread effects of senescent cells on tissue decline."

Senescent cells, which are permanently arrested because of chronic stress, are partly responsible for tissue decline during aging.

"Stem cells last throughout life and, like us, are subjected to the ravages of aging, environmental stressors, and deterioration of the machinery that enables them to function optimally," Kaplan explains. "To survive, many stem cells revert to a dormant, unresponsive, and inactive state. Our goal was to wake up these dormant cells and, in doing so, enable them to carry out their biological functions that facilitate learning, memory, and brain repair."

They observed an aging-dependent accumulation of senescent cells, largely senescent stem cells, within the hippocampal stem cell niche coincident with declining adult neurogenesis. Pharmacological ablation of the senescent cells via a drug called ABT-263 caused a rapid increase in normal stem cell proliferation and neurogenesis, and genetic ablation of senescent cells similarly activated hippocampal stem cells.

This burst of neurogenesis had long-term effects in middle-aged mice. One month after treatment with ABT-263, adult-born hippocampal neurons increased and hippocampus-dependent spatial memory was enhanced. "The surprise for us is that only one injection of the drug was sufficient to mobilize the normal stem cells in the hippocampus, and it did so after only 5 days," Kaplan says. "The newly awakened stem cells continued to function well for the next 30 days."

[ConservativeMind]

There are multiple senolytic supplements, including quercetin, fisetin, Piperlongumine, among others. Of these, fisetin is likely the best singular senolytic that does not require a prescription.

[ConservativeMind]

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