autophagy senescence glaucoma

# Introduction Glaucoma is a leading cause of irreversible blindness, marked by progressive death of retinal ganglion cells (RGCs) and damage to the optic nerve. It often involves elevated intraocular pressure (IOP) due to dysfunction in the **trabecular meshwork** (TM) outflow system, as well as age‐related neurodegeneration of RGC axons. Age is the strongest risk factor: aging causes oxidative stress, mitochondrial decline, accumulation of damaged proteins and cells, and chronic inflammation – all of which contribute to glaucoma pathophysiology ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC9795220/#:~:text=Autophagy%20is%20a%20highly%20conserved,18%20Nixon%20et%20al)) ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC10917531/#:~:text=The%20potential%20mechanisms%20underlying%20glaucomatous,the%20pivotal%20role%20of%20cellular)). Biologists studying aging (“longevity pathways”) have identified key regulators – **AMPK**, **mTOR**, **sirtuins**, **autophagy**, and **cellular senescence** – that govern metabolic health and tissue maintenance. These pathways overlap with mechanisms in glaucoma: for example, autophagy dysfunction and inflammation are linked to both neuronal loss and TM failure ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC9795220/#:~:text=Autophagy%20is%20a%20highly%20conserved,18%20Nixon%20et%20al)) ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC10917531/#:~:text=Senescent%20trabecular%20meshwork%20,to%20ameliorate%20RGC%20death%20and)). Translational research now asks whether nutrition or supplements that modulate these pathways can protect the aging optic nerve and TM. This article maps each core pathway to glaucoma biology, highlights supplements that influence them, and suggests biomarkers (like NAD⁺ levels, cytokines, and OCT imaging) to measure effects. We also discuss critical gaps – notably, the lack of controlled trials comparing these supplements to standard IOP‐lowering care – that must be addressed to move from bench to bedside. ## Longevity Pathways in Glaucoma Pathophysiology ### Energy Sensing: AMPK and mTOR **AMPK** (adenosine monophosphate–activated protein kinase) and **mTOR** (mechanistic Target of Rapamycin) are nutrient/energy sensors that regulate cell survival and growth. AMPK is activated by low energy (high AMP/ADP) and promotes catabolism and autophagy, whereas mTOR is active with abundant nutrients and encourages growth and protein synthesis. In aging tissues, AMPK signaling tends to decline while mTOR signaling is relatively enhanced ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC9795220/#:~:text=match%20at%20L276%20Aging%20,2022)), suppressing autophagy and stress resistance. In glaucoma, dysregulated AMPK/mTOR contributes to disease: for example, increased mTOR activity can drive fibrotic scarring in the optic nerve head and TM extracellular matrix, worsening IOP elevation and axonal injury ([pmc.ncb

From Bench to Bedside: Translating Longevity Pathways to Glaucoma Supplements

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