Cellular Senescence Triggered by Food and Environmental Genotoxins.

Area of Science:

• Cellular and Molecular Biology
• Toxicology
• Gerontology

Background:

• Cellular senescence (CSEN) is a complex process triggered by various stressors, including DNA damage from genotoxins.
• Exogenous genotoxins from environmental and dietary sources are increasingly recognized as inducers of CSEN.
• CSEN is implicated in aging, organ failure, and age-related diseases through the senescence-associated secretory phenotype (SASP).

Purpose of the Study:

• To review the induction of cellular senescence by exogenous genotoxic insults from food and environmental exposures.
• To highlight the molecular pathways involved in CSEN induction by these external factors.
• To discuss the implications of CSEN for aging and organ function.

Main Methods:

• Literature review of studies investigating CSEN induction by exogenous genotoxins.
• Analysis of data on genotoxins present in tobacco, food, beverages, and lifestyle products.
• Examination of the molecular mechanisms, including DNA damage response (DDR) pathways.

Main Results:

• Genotoxins/carcinogens in tobacco smoke, environment, food, and lifestyle products induce CSEN.
• Identified genotoxins include N-nitroso compounds, PAHs, HACs, acrylamide, heavy metals, and mycotoxins.
• CSEN induction by genotoxins involves DDR pathways (ATM/ATR-CHK2/CHK1-p53-p21, p53-independent p16/p14) and other signaling cascades.

Conclusions:

• Exogenous genotoxins significantly contribute to CSEN induction, potentially exacerbating aging and organ failure.
• The role of CSEN induced by dietary and environmental genotoxins is likely underestimated.
• Reducing genotoxin exposure and utilizing senotherapeutics are proposed strategies to mitigate CSEN and aging.