Age-Associated Impairment of Human Tissue Regeneration: Contribution of Key Aging Mechanisms

Abstract

Elucidating the mechanisms underlying the progressive loss of tissue regenerative capacity during aging constitutes a fundamental challenge in contemporary science. Although individual aging mechanisms have been extensively characterized, studying them separately fails to reveal how these mechanisms jointly contribute to the decline in tissue regeneration. The present review offers a systems-level perspective, integrating key cellular and molecular aging processes into an interconnected network instead of describing each one separately. We demonstrate that age-associated regenerative decline does not arise from a single dominant defect but from a complex multi-layered interplay that generates self-reinforcing pathological loops, wherein each component exacerbates the others. These interactions manifest as organ-specific patterns of regenerative failure across the heart, liver, kidneys, lungs, bone, skin, skeletal muscle, and brain. Consequently, age-related regenerative impairment represents a systemic phenomenon whose effective management requires integrative therapeutic strategies that concurrently target multiple critical nodes within the pathological network.