Hallmarks of Skin Aging: Update.

Aging is defined as impaired physiological integrity, decreased function, increased susceptibility to external risk factors and various diseases. Skin, the largest organ in our body, may become more vulnerable to insult as time goes by and behave as aged skin. Here, we systemically reviewed three categories including seven hallmarks of skin aging. These hallmarks including genomic instability and telomere attrition, epigenetic alterations and loss of proteostasis, deregulated nutrient-sensing, mitochondrial damage and dysfunction, cellular senescence, stem cell exhaustion/dysregulation, and altered intercellular communication. These seven hallmarks can generally be divided into three categories including (i) causes of damages as primary hallmarks in skin aging; (ii) responses to damage as antagonistic hallmarks in skin aging; and (iii) culprits of the phenotype as integrative hallmarks in skin aging.