sirtuin

# Resveratrol’s Promise in Glaucoma: Ocular Cells and Systemic Aging **Resveratrol** is a polyphenolic compound often touted as a “caloric restriction mimetic” and **SIRT1** activator with antioxidant and anti-inflammatory effects. Early studies showed resveratrol can boost stress resistance and extend lifespan in organisms from yeast to mammals ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC2674270/#:~:text=polyphenol%20found%20in%20berries%2C%20nuts%2C,25%20Kahn%2C%20et%20al)). In cells and animal models, resveratrol activates SIRT1 – a deacetylase linked to longevity – which in turn induces **autophagy** (cellular cleanup) required for its healthspan benefits ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC3032517/#:~:text=Caloric%20restriction%20and%20autophagy,elegans)). These same pathways – reduced oxidative stress, enhanced cellular renewal – underlie interest in resveratrol for age-related eye diseases. In glaucoma, where **trabecular meshwork (TM)** cells and retinal ganglion cells (RGCs) suffer chronic stress and senescence, resveratrol’s anti-aging mechanisms are being explored. ## Trabecular Meshwork: Fighting Senescence and Stress The TM tissue acts as the eye’s drainage filter and becomes less cellular and more dysfunctional in glaucoma. Chronic oxidative stress and inflammation in TM cells trigger senescence (marked by SA-β-gal, lipofuscin) and cytokine release (IL-1α, IL-6, IL-8, ELAM-1). In cultured TM cells subjected to high oxygen stress, chronic resveratrol (25 µM) virtually **abolished the rise in reactive oxygen species (ROS)** and inflammatory markers, and sharply **reduced senescence markers** ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC2674270/#:~:text=TM%20cells%20subjected%20to%20chronic,tissue%20abnormalities%20observed%20in%20POAG)). In one study, resveratrol-treated TM cells had much lower SA-β-gal activity and protein carbonylation despite oxidative challenge ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC2674270/#:~:text=TM%20cells%20subjected%20to%20chronic,tissue%20abnormalities%20observed%20in%20POAG)). This suggests resveratrol may preserve TM cell health by blocking stress-induced aging. Resveratrol also influences Nitric Oxide (NO) pathways in TM cells. In glaucomatous human TM cells, resveratrol increased endothelial NO synthase (eNOS) expression and boosted NO levels, while lowering inducible NOS (iNOS) at higher doses ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC6566435/#:~:text=eNOS%2C%20and%20reduction%20in%20iNOS,RSV%E2%80%99s%20antioxidant%20capabilities%20in%20vision)). Since NO promotes blood flow and may reduce outflow resistance, increased NO could improve ocular perfusion and outflow facility. Likewise, lowering iNOS (which drives damaging oxidative stress) underscores resveratrol’s antioxidant role ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC6566435/#:~:text=eNOS%2C%

Resveratrol and Sirtuin Pathways: From Trabecular Meshwork to Longevity

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