Principles of the Molecular and Cellular Mechanisms of Aging

Aging can be defined as a state of progressive functional decline accompanied by an increase in mortality. Time-dependent accumulation of cellular damage, namely lesions and mutations in the DNA and misfolded proteins, impair organellar and cellular function. Ensuing cell fate alterations lead to the accumulation of dysfunctional cells and hamper homeostatic processes, thus limiting regenerative potential; trigger low-grade inflammation; and alter intercellular and intertissue communication. The accumulation of molecular damage together with modifications in the epigenetic landscape, dysregulation of gene expression, and altered endocrine communication, drive the aging process and establish age as the main risk factor for age-associated diseases and multimorbidity.