Modern Rejuvenation and Anti-Aging Therapies: Molecular Mechanisms, Risk Factors, Current Interventions, and Future Technological Directions

Abstract

Aging is the dominant risk factor for most chronic diseases and functional decline, yet it is increasingly understood not as a passive process, but as a biologically regulated and partially plastic trajectory. Contemporary geroscience has reframed aging as a network phenomenon driven by interacting hallmarks that include genomic instability, telomere attrition, epigenetic drift, loss of proteostasis, impaired autophagy, mitochondrial dysfunction, deregulated nutrient sensing, cellular senescence, stem cell exhaustion, chronic low-grade inflammation, altered intercellular communication, and microbiome dysregulation (López-Otín et al., 2013; López-Otín et al., 2023). This framework has enabled the emergence of rejuvenation-oriented strategies that aim either to slow the rate of damage accumulation or to reverse selected biological features of aging. Modern interventions span lifestyle measures such as exercise and fasting-related regimens, pharmacological gerotherapeutics including metformin, rapalogs, senolytics, and NAD+-modulating compounds, as well as more experimental approaches such as partial epigenetic reprogramming, cell-free regenerative therapies, and plasma or proteome-based rejuvenation (Barzilai et al., 2016; Guarente et al., 2024; Kerepesi et al., 2024).
This review examines the molecular basis of aging and rejuvenation, the principal biological and environmental risk factors that accelerate aging, and the evidence supporting current anti-aging interventions. Particular attention is given to nutrient-sensing pathways, mitochondrial quality control, the senescence-associated secretory phenotype, immune aging, and stem cell niche failure. The review also addresses biological age assessment, including epigenetic clocks and broader biomarker frameworks, which are increasingly central for clinical translation and intervention testing (Bell et al., 2019; Horvath, 2013; Levine et al., 2018; Moqri et al., 2023). Although progress has been substantial, most rejuvenation technologies remain limited by incomplete long-term safety data, tissue specificity, uncertain durability, and regulatory complexity. The field is therefore at a transitional stage: no single therapy currently reverses systemic human aging, but convergent evidence suggests that combination approaches, biomarker-guided personalization, and safer genetic and epigenetic engineering may define the next era of longevity medicine. Future progress will likely depend on precision geroscience, validated aging clocks, and interventions designed to restore resilience rather than merely suppress isolated disease endpoints (Kennedy et al., 2014; Seals et al., 2016).