Cellular Senescence
The zombie cells. Senescent cells have stopped dividing but resist death. They accumulate with age and secrete inflammatory factors (SASP) that damage surrounding tissue. Clearing senescent cells with senolytics is a promising anti-aging strategy.
What Is Senescence?
Cell Cycle Arrest
Cells permanently stop dividing. Originally protective against cancer. But they persist.
Resist Death
Unlike apoptosis. Don't die and get cleared. Accumulate in tissues.
SASP
Senescence-associated secretory phenotype. Inflammatory cytokines, proteases. Damages neighbors.
Why Senescent Cells Are Harmful
Chronic Inflammation
SASP includes IL-6, IL-8, TNF-α. Constant low-grade inflammation. Inflammaging.
Tissue Dysfunction
Matrix metalloproteinases degrade tissue. Loss of function. Organ decline.
Spread Senescence
SASP induces senescence in neighbors. Bystander effect. Contagious aging.
Stem Cell Exhaustion
SASP signals exhaust stem cells. Reduced regeneration. Healing slows.
Cancer Promotion
Paradoxically, while preventing cancer in cell, SASP promotes it in neighbors.
Frailty
Accumulation correlates with frailty. Muscle weakness, fatigue, slow walking.
Clearing Senescent Cells
Quercetin + Dasatinib
First senolytic combo studied. Quercetin is OTC. Dasatinib is prescription cancer drug.
Fisetin
Found in strawberries. Natural senolytic. Human trials underway. Promising.
Navitoclax
BCL-2 inhibitor. Potent senolytic. Side effects limit use. Research ongoing.
Exercise
May reduce senescent cell burden. Immune clearance improved. Best prevention.
Fasting
Autophagy may clear some. Reduces SASP. Immune system clearance.
Intermittent Dosing
Senolytics taken occasionally. "Hit and run" approach. Once cells die, done.