Effect of DNA damage mediating psychosocial stress on aging

Abstract

Adversity and psychosocial stress are involved in aging through the following pathways. psychological stress enhances the nerve system to secrete endocrine mediators (hormones). Mitochondrial respiration mediates energy production stimulated by binding to these hormones to their receptors. Energy produced by mitochondria accelerates metabolism and, in its turn, leads to increases in reactive oxygen species (ROS) of free radicals. Cellular stress and accumulation of damage can result from an excess of ROS. Accumulation of damage comprises damages in telomeric and nontelomeric DNA, in addition to mitochondrial DNA. Mitochondrial DNA damage plays an important role in increasing the pathway of p53/p21. The expression of the PGC-1α gene is inhibited by activation of the previous pathway that generates a decrease in mitochondrial biogenesis. The low level of mitochondrial biogenesis generates mitophagy defects and increases the level of dysfunctional mitochondria that lead to a high level of ROS production. Nuclear DNA damage and mitochondrial dysfunction stimulate necrosis or cell senescence. Necrotic cells enhance the inflammatory activity by which damage-associated molecular patterns (DAMPs) are continuously secreted. Senescent cells secrete high levels of the senescence-associated secretory phenotype (SASP) that includes tumor necrosis factor TNF-α and interleukin-6 (IL-6) as inflammatory cytokines, and MCP-2 and interleukin-8 (IL-8) as chemokines. All these processes work together to accelerate the biological aging process by causing defects related to aging such as diabetes and cardiovascular disease.