Cellular Senescence Triggered by Food and Environmental Genotoxins

Abstract

Cellular senescence (CSEN) is caused by a variety of factors that trigger complex molecular pathways. These include telomere shortening, oncogene activation and replicative stress, as well as DNA damage caused by genotoxic anticancer drugs and endogenous and exogenous genotoxins. Here, we review the induction of CSEN by exogenous genotoxic insults resulting from food and environmental exposures. The available data show that genotoxins/carcinogens in tobacco smoke and smokeless tobacco, in the environment, in food, beverages and life-style products induce CNS. The exposures include N-nitroso compounds, polycyclic aromatic hydrocarbons, heterocyclic aromatic amines, acrylamide, heavy metals, fine dust, mycotoxins, phytotoxins, and phycotoxins. Also, heme in red meat contributes to CSEN as it catalyzes the formation of genotoxic species in the colon. Induction of CSEN by external genotoxins/carcinogens is bound on the DNA damage response pathway (DDR), which relies on activation of the ATM/ATR-CHK2/CHK1-p53-p21 axis and the p53-independent p16/p14 axis, eliciting cyclin-dependent kinase inhibition and permanent cell cycle arrest. Other factors that can be involved are DREAM, MAPK, cGAS/Sting, and NF-κB. The accumulation of non-repaired DNA damage triggering CSEN following external genotoxic exposures may contribute significantly to the amelioration of senescent cells and organ failure with age in humans. Senescent cells drive, via the senescence-associated secretory phenotype (SASP), inflammation that is involved in many diseases, including cancer. Although most of the studies were performed with in vitro cell systems, the consequences of CSEN induction by genotoxic nutritional components and environmental exposures seem to be underestimated. Since CSEN correlates with aging, it is reasonable to conclude that exogenous genotoxic pollutants contribute significantly to the aging process through CSEN induction. In light of these findings, it is deduced that reducing genotoxin exposures and using “rejuvenation” supplements (senotherapeutics) are reasonable strategies to counteract cellular senescence and the aging process.