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Growth Factor Implicated in Aging

Inhibitor tamps down TGF-beta1 and rejuvenates aging stem cells in brain and muscles, in a lab animal model.

The failure of adult stem cells to generate replacements for damaged cells and thus repair the body’s tissues is thought to be a major mechanism of aging.  Previous studies suggest that this decreased stem cell activity is largely a result of inhibitory chemicals in the environment around the stem cell, some of them dumped there by the immune system as a result of chronic, low-level inflammation that is also a hallmark of aging. David Schaffer and Yousef H, Conboy, from the University of California/Berkeley (UCB; California, USA), and colleagues previously explored  the growth factor TGF-beta1, which depresses the ability of various types of stem cells to renew tissue.  In the brain’s hippocampus, TGF-beta1 activity associates with memory and learning. Among the hallmarks of aging are a decline in learning, cognition and memory. In the present study, the team showed that in old mice, the hippocampus has increased levels of TGF-beta1 similar to the levels in the bloodstream and other old tissue. The investigators then injected into the blood a chemical known to block the TGF-beta1 receptor and thus reduce the effect of TGF-beta1. This small molecule, an Alk5 kinase inhibitor already undergoing trials as an anticancer agent, successfully renewed stem cell function in both brain and muscle tissue of the same old animal.  The study authors submit that: “These findings suggest that at high levels typical of aged tissues, TGF-beta1 promotes inflammation instead of its canonical role in attenuating immune responses.”

Yousef H, Conboy MJ, Morgenthaler A, Schlesinger C, Bugaj L, Paliwal P, Greer C, Conboy IM, Schaffer D.   “Systemic attenuation of the TGF-[beta] pathway by a single drug simultaneously rejuvenates hippocampal neurogenesis and myogenesis in the same old mammal.” Oncotarget. 2015 May 20;6(14):11959-78.

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