[Aging--from the molecule to the organism]

Area of Science:

• Gerontology and Molecular Biology
• Cellular and Organismal Aging Research

Background:

• Aging manifests heterogeneously at molecular, cellular, and organismal levels.
• Numerous aging theories exist, but robust evidence for programmed vs. random changes is lacking.
• Cellular senescence, characterized by limited division potential, serves as a model for aging.

Purpose of the Study:

• To explore the central role of DNA damage and repair in cellular senescence.
• To investigate the relationship between DNA repair capacity and maximum species lifespan.
• To discuss age-related changes in key organs and organismal aging aspects like multimorbidity.

Main Methods:

• Review of recent studies on DNA damage, repair, and cellular senescence.
• Analysis of in vitro fibroblast division potential in relation to donor age.
• Discussion of age-related physiological changes in brain, heart, liver, and locomotory systems.

Main Results:

• A direct relationship exists between DNA repair capacity and maximum species lifespan.
• Fibroblasts from younger individuals exhibit greater proliferative capacity than those from older individuals.
• Organ-specific aging and organismal aging phenomena like multimorbidity and altered pharmacokinetics are observed.

Conclusions:

• DNA damage and repair mechanisms are critical determinants of cellular senescence and aging.
• Cellular aging models, like fibroblast division potential, reflect organismal aging.
• Understanding aging requires integrating molecular, cellular, and organ-level perspectives, including disease.