Cellular Senescence Reduction

Cellular senescence is a permanent exit from the cell cycle triggered by telomere shortening, DNA damage or oncogene activation. It evolved as a tumour suppression mechanism, but senescent cells resist apoptosis and accumulate with age, particularly in adipose tissue, skin and joints. They secrete the senescence-associated secretory phenotype: interleukin-6, interleukin-1beta, TNF-alpha and matrix metalloproteinases that inflame surrounding tissue and induce senescence in neighbouring cells. The causal evidence in animals is unusually strong: transgenic mice allowing clearance of p16-positive cells showed delayed age-related pathology and extended median lifespan, and transplanting senescent cells into young mice induces physical dysfunction. Human evidence is far earlier — small open-label trials of dasatinib plus quercetin have reduced senescent markers in adipose tissue and improved walk distance in pulmonary fibrosis, but no trial has shown healthspan or mortality benefit.

Exercise is the intervention with real human data: both aerobic and resistance training reduce p16 expression and SASP markers reproducibly. Maintain a healthy body composition, since adipose tissue is a principal reservoir of senescent cells. Avoid the accelerators — smoking, excess UV exposure, chronic hyperglycaemia and chemotherapy all increase senescent burden. Among interventions under investigation, fisetin at 20 mg/kg for two to three consecutive days on an intermittent schedule is the most accessible senolytic candidate, dasatinib plus quercetin is the combination used in human pilot trials but dasatinib is a prescription chemotherapy agent requiring supervision, and metformin, rapamycin and spermidine act more as senomorphics that suppress the secretory phenotype without killing the cells. Anyone considering senolytics should understand they are participating in an experiment rather than following established medicine.

• •Regular aerobic and resistance training, which reduces senescence markers
• •Maintaining low visceral adiposity
• •Stopping smoking
• •Sun protection to limit UV-induced dermal senescence
• •Maintaining good glycaemic control
• •Adequate sleep, which supports DNA repair