Biochem Biophys Res Commun. 2025 Sep 25. pii: S0006-291X(25)01424-X. [Epub ahead of print]785 152708
Contemporary gene therapy approaches represent a promising avenue for intervening in aging mechanisms and treating age-associated diseases. This review analyzes findings from preclinical and clinical studies of gene therapeutic strategies targeting age-related pathologies, including neurodegenerative, cardiovascular, metabolic, and ophthalmological disorders. We examine how specific aging mechanisms - DNA damage accumulation, telomere attrition, mitochondrial dysfunction, and chronic inflammation - can be addressed through targeted gene therapies. Key therapeutic targets include telomerase reactivation through TERT overexpression for genomic stability, KLOTHO supplementation for anti-inflammatory effects, metabolic regulation via SIRT family genes and FoxO3, and protein homeostasis modulation through APOE variants. Additional approaches encompass growth differentiation factors such as GDF11 for tissue regeneration, senolytic strategies for eliminating senescent cells, and epigenetic reprogramming techniques for tissue rejuvenation. Rather than characterizing these as universal 'longevity genes,' we emphasize their context-dependent effects, disease-specific applications, and associated benefit-risk profiles. Current methodological limitations and promising directions for developing personalized gene therapy interventions targeting the biological processes underlying aging are discussed.
Keywords: Age-related diseases; Aging mechanisms; Cellular senescence; Delivery systems; Gene therapy