Study finds that aging neurons accumulate DNA damage
The progression of age is a multifaceted phenomenon that manifests itself in a decrease in the body’s ability to re-establish its internal balance after aggressions, consequently increasing the likelihood of illness and death. Various elements contribute to ageing, such as the gradual accumulation of damage to large molecules over time, including damage to genetic material. The integrity of the genome present in the nucleus of cells is fundamental to the health of cells, tissues and the organism as a whole.
DNA damage represents a constant threat, since nucleic acids are intrinsically unstable under physiological conditions and susceptible to aggression from internal and external factors. To counteract this threat, all living beings have highly preserved defense systems to identify and correct DNA damage. Persistent DNA damage, a condition known as genotoxic stress, triggers signaling sequences that lead cells to self-destruct (apoptosis) or to a state of dormancy (senescence), thus preventing the replication of a compromised genome. However, this cancer prevention strategy has a side effect: the stimulation of ageing.
In this analysis, we examine evidence that supports the causal role of DNA damage in the aging process. Additionally, we present data connecting genotoxic stress to other cellular processes recognized as drivers of aging, including mitochondrial and metabolic malfunction, alterations in protein maintenance (proteostasis) and inflammation. These interconnections between damage to the genetic code and other pillars of ageing reinforce the idea that DNA damage may be at the root of the ageing process.