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Aging, Senescence, and GlaucomaGlaucoma is a leading cause of blindness and its risk rises with age. In aged eyes, cells can enter a senescent state – they stop dividing but stay alive – and release harmful signals called the senescence-associated secretory phenotype (SASP). Senescent cells in the eye can worsen disease. For example, aged trabecular meshwork cells (the filter in front of the eye) become stiff and clogged, raising eye pressure (). In the retina and optic nerve, senescent cells release cytokines (like IL-6, IL-8, IL-1β) and enzymes (MMPs) that cause inflammation, tissue remodeling, and nerve cell death () (). These SASP factors have been found in human glaucomatous eyes and animal models of eye pressure, where they drive retinal ganglion cell (RGC) damage () (). Targeting these cells is a new idea: removing or quieting them may help protect the optic nerve.Senescence in the EyeSenescent cells build up in key eye tissues. In the trabecular meshwork (TM), senescence stiffens the meshwork and increases resistance to fluid outflow (). This raises intraocular pressure, a main risk factor for glaucoma. In humans with glaucoma, more senescent TM cells (marked by enzymes like SA-β-gal, or proteins p16^INK4a and p21^CIP1) have been measured compared to normal eyes (). High p16 and p21 in TM cells correlate with glaucoma and fewer TM cells survive into old age (). In the optic nerve head and retina, aging and stress cause RGCs and supporting cells (astrocytes, microglia) to become senescent. These cells then secrete SASP factors – pro-inflammatory cytokines (IL-6, IL-1β, IL-8), chemokines (CCL2, CXCL5), and matrix metalloproteinases – which poison nearby neurons and propagate senescence to neighbors () (). In mouse models of high eye pressure and in human glaucoma tissue, elevated levels of IL-6, IL-1β, IL-8 and other SASP markers have been found, linked to chronic inflammation and RGC death (). Thus, senescence and SASP contribute to TM dysfunction and optic nerve damage in glaucoma.Quercetin and Fisetin as SenolyticsSenolytic drugs are agents that kill senescent cells, while senomorphics suppress their harmful secretions. Quercetin and fisetin are natural flavonoids with senolytic or senomorphic activity. Quercetin is found in many fruits and vegetables and is known as an antioxidant. Research shows quercetin can selectively eliminate senescent cells and tone down the SASP (). It has anti-inflammatory and anti-oxidant properties in the eye as well. In models of retinal stress, quercetin increases protective enzymes (like Nrf2 and HO-1) and reduces cell death (). As a senolytic, quercetin suppresses NF-κB (a key SASP regulator) and lowers secretion of IL-6 and other cytokines from senescent cells (). Fisetin, a sibling of quercetin, is emerging as a powerful senolytic. In one report, fisetin outperformed quercetin in killing senescent cells in culture and mice (). Fisetin treatment in old mice reduced p16^INK4a and other senescence markers in tissues, improved health span, and extended lifespan () (). Fisetin is already used as a dietary supplement and appears safe. Its strong senolytic effect suggests it might clear senescent eye cells too. Both quercetin and fisetin have favorable safety profiles in humans, so they are attractive for trials () (). Preclinical Evidence in GlaucomaIn glaucoma models, removing senescent cells has shown clear benefit. In a mouse model of acute ocular hypertension, many RGCs became senescent and activated SASP genes after eye
