This review synthesizes current evidence on whether a NAD+–sirtuin–mitochondrial quality control (MQC) network in lens epithelial cells (LECs) acts as a modulator of crystalline lens aging, encompassing presbyopia and age-related cataract.
Evidence supports age-associated declines in mitochondrial oxygen consumption in primary human LECs, SIRT1-linked stress tolerance, and PINK1/Parkin-dependent mitophagy as protective mechanisms, but a causal link from LEC NAD+ depletion to tissue-level lens aging remains unproven.
Age-dependent NAD+ changes in normal human LECs have not been directly measured; no causal epithelial-to-tissue pathway has been established; the review proposes but does not execute the three experimental validation levels it describes.
There is no practice-ready intervention from this review; it frames NAD+ homeostasis in LECs as a testable—but not yet proven—target for lens aging research, and clinicians should await prospective experimental validation before considering NAD+-based strategies for presbyopia or cataract.
