Rewinding the Clock: Emerging Pharmacological Strategies for Human Anti-Aging Therapy

Aging is a complex, multifactorial process characterized by progressive physiological decline and increased vulnerability to chronic diseases and syndromes. Recent studies have highlighted nine interrelated telomere(definition) attrition, cellular senescence(definition))." style="text-decoration:underline dotted; text-underline-offset:2px; cursor:help;">hallmarks of aging(definition), emerging primarily from an understanding of cellular homeostasis, health, and senescence, such as genomic instability, telomere attrition, and cellular senescence. These hallmarks provide a conceptual framework for advancing pharmacotherapeutic interventions. In this review, we present an overview of old and new pharmacotherapeutic interventions that are being developed using these hallmarks of aging to enhance healthspan(definition) delay and ameliorate age-related pathologies. We classify these strategies into five broad categories, including senolytics(definition), senomorphics, NAD+ precursors, mTOR(definition) inhibitors, and metabolic modifiers, such as metformin, and review the mechanisms by which they act, preclinical evidence for efficacy, and their translational potential to a clinical context. In addition, we consider the clinical landscape and report the important trials that are currently underway and some of the main obstacles, including key challenges such as biomarker identification, safety issues, and regulatory challenges. Overall, we discuss ahead-of-time gerotherapeutics and the important role of a collective, mechanism-focused basis for therapeutically targeting aging biology.