Figure 1. DNA damage is the driver of ageing.

The nuclear and mitochondrial genomes are continuously damaged by exogenous agents (UV, X-rays, chemical compounds in food, water, air), endogenous sources such as reactive oxygen species (ROS), aldehydes and advanced glycation endproducts (AGEs) and spontaneous reactions (hydrolysis). Molecular consequences of time-dependent accumulating DNA damage are: i) genetic aberrations, such as mutations and chromosomal instability, and ii) stalling of RNA and DNA polymerases by DNA lesions, which provokes DNA damage signaling and interferes with primary DNA functioning. Cellular and tissue consequences of DNA damage include cell fate decisions such as cell death and senescence leading to functional loss of cells and organs, cancer, atrophy and inflammation.