MECANISMOS MOLECULARES DO ENVELHECIMENTO HUMANO: DOS HALLMARKS À SENESCÊNCIA NEGLIGENCIÁVEL

Biological aging is currently redefined by translational biogerontology as the progressive decline of cellular homeostasis, driven by the accumulation of stochastic molecular damage - a process whose partial reversibility has been demonstrated at the epigenetic and molecular level in pre-clinical models. This narrative review analyzes the fundamental molecular mechanisms of human aging through the hallmarks framework (LÓPEZ-OTÍN et al., 2013; 2023). Core domains include: genomic instability and telomere(definition) attrition, cellular senescence(definition) coupled with the Senescence-Associated Secretory Phenotype (SASP), metabolic dysregulation of the mTOR(definition)/IGF-1 axis, autophagic insufficiency, and proteostatic failure. Evidence of negligible senescence in Turritopsis dohrnii, Hydra sp., and Heterocephalus glaber, alongside regenerative competence across taxa, indicates that senescence-induced mortality is not a universal biological constraint. The concept of amortality - the absence of intrinsic age-related functional decline while retaining exogenous vulnerability - is discussed as a translational horizon of modern geroscience. It is concluded that the mechanistic drivers of aging exhibit therapeutic modulability, and that geroprotective interventions represent a relevant frontier for extending the healthy lifespan (healthspan(definition)).