Reversing Cellular Senescence is a clinical and scientific objective focused on eliminating or functionally rejuvenating senescent cells, which are cells that have permanently ceased dividing but remain metabolically active and secrete pro-inflammatory molecules known as the Senescence-Associated Secretory Phenotype (SASP). Senescent cells accumulate with age and contribute significantly to tissue dysfunction, chronic inflammation, and the pathology of multiple age-related diseases. Therapeutic strategies aim to clear these detrimental cells or reprogram them to a non-senescent state, thereby improving tissue function and extending healthspan. This is a direct intervention into a fundamental mechanism of biological aging.
Origin
This concept originates from the field of rigorous geroscience, following the pivotal discovery of cellular senescence as a fundamental mechanism of aging and age-related disease. The term “Reversing” reflects the development of novel therapeutic classes, such as senolytics (drugs that selectively kill senescent cells) and senomorphics (drugs that suppress the SASP), moving the goal from merely studying aging to actively intervening in its core cellular mechanisms.
Mechanism
The mechanism of reversal primarily involves two therapeutic approaches: senolysis, which selectively induces apoptosis in senescent cells by targeting their anti-apoptotic pathways, and senomorphics, which modulate the senescent cell’s secretome to significantly reduce its inflammatory impact on surrounding tissue. By reducing the overall senescent cell burden, clinicians aim to restore tissue homeostasis, mitigate chronic systemic inflammation, and enhance the regenerative capacity of the remaining healthy cells.
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