Accelerated biological aging: the role of chronic inflammation, weathering and novel therapeutic strategies.

Abstract

Biological aging is a gradual, multisystem process characterized by progressive functional decline, diminished physiological resilience, and increased susceptibility to chronic diseases. Growing evidence suggests that persistent exposure to adverse social environments, chronic psychological stress, and socioeconomic disadvantage can accelerate biological aging by altering age-related biomarkers and stress-response pathways. The weathering hypothesis provides a framework to explain how the cumulative burden of psychosocial adversity becomes biologically embedded, resulting in physiological wear and tear that hastens age-related deterioration over time. A central mechanism underlying this process is chronic low-grade inflammation, which contributes to the pathogenesis of numerous age-related conditions, including cancer and neurodegenerative diseases (NDDs). These disorders are highly prevalent among Caribbean Hispanics, a population disproportionately affected by social disadvantages and rapid population aging. Recent advances in the biology of inflammation and cellular senescence have generated interest in therapeutic strategies aimed at modulating fundamental mechanisms of aging. Emerging approaches, including senolytics, anti-inflammatory agents, and non-coding RNA-based interventions, offer promising opportunities for precision medicine; however, RNA-based therapies remain largely experimental, and their clinical translation to address stress-related aging and health disparities has yet to be established. In this review, we examine the interplay between weathering and inflammation in shaping biological aging and discuss the potential of innovative precision medicine approaches to mitigate age-related decline and reduce health disparities in vulnerable populations.