Rapamycin Inhibits The Effects Of Senescent Cells

Senescent fibroblast. Credit: Glyn Nelson/Flickr

Senescent fibroblast. Credit: Glyn Nelson/Flickr

Rapamycin may be able to block the harmful, inflammatory signalling of senescent cells through two distinct mechanisms

Rapamycin is one of the most well known, and promising, longevity drugs under study. Previous work has revealed it could impact on something called the senescence-associated secretory phenotype, or SASP. This is essentially what makes senescent cell such bad news; consisting of inflammatory signals that break down tissue and may even contribute to cancer risk as well as driving body wise, systemic inflammation. It was believed that rapamycin was able to do this through one distinct mechanism - upregulating a regulator called Nrf2. Nrf2 is involved with a large range of processes from detoxification to repair and metabolism and controls over 200 genes. We know that its activation is able to dampen down this harmful SASP. 

"The increase in cellular senescence associated with aging, and the inflammation associated with that, can help set the stage for a wide variety of degenerative disease, including cancer, heart disease, diabetes and neurologic disease, such as dementia or Alzheimer's. In laboratory animals when we clear out senescent cells, they live longer and have fewer diseases. And rapamycin can have similar effects"

A new direct mechanism

New research has revealed that rapamycin actually acts through an additional mechanism too and is actually able to directly act on the SASP itself through another pathway called the STAT3 pathway. This reveals that rapamycin acts via a two-pronged approach and effectively inhibiting the SASP produced by senescent cells. 

"Any new approach to help protect neurons from damage could be valuable. Other studies, for instance, have shown that astrocyte cells that help protect neuron function and health can be damaged by SASP. This may be one of the causes of some neurologic diseases, including Alzheimer's disease"

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