| Popis: |
Aging is a central risk factor for many age-related pathologies including cancer, cardiovascular disease, and autoimmune disease. Therefore, a mechanistic understanding of the aging process promises great potential for discoveries of therapeutic measures that can relieve the burden of age-related pathologies. According to the “DNA damage accumulation theory of aging,” the accumulation of unrepaired DNA damage and resulting genomic instability plays a central role in promoting aging. In line with this, numerous DNA-repair diseases are characterized by increased genomic instability and recapitulation of several symptoms of normal aging. Numerous intrinsic and extrinsic factors contribute to age-dependent DNA damage accumulation, including oxidative stress, DNA replication errors, deteriorating genome-maintenance mechanisms, altered nuclear organization, and survival in presence of DNA damage. This negatively affects cell and tissue homeostasis through causing changes in gene expression profiles, or inducing cellular senescence or apoptosis, thereby promoting functional decline of tissue function, which is characteristic for aging. |
