The gut microbiota is responsible for the age-dependent decline of DNA damage repair.
The ageing process is caused by the failure to repair DNA damage. Age-related inflammation also contributes to ageing. Recent studies have shown that repair efficiency of double-strand break (DSB) caused by diethylnitrosamine, a DEN-based compound, rapidly decreases with age. We hypothesized that the age-related inflammation is responsible for the decrease in DNA damage repair.
Design We compared the effectiveness of the resolution of DEN-induced damage to the DNA in the livers at different ages, and after various permutations aimed to manipulate the age-related inflammation in the liver.
Results We found that altered gut microbiota was associated with age-related deregulations of innate immunity. Consequently, MyD88 ablation, antibiotic treatment or germ-free mouse had reduced cytokine production and improved DSBs joining in 6-month-olds mice. A high-fat diet for young mice increased inflammation and facilitated DSB repair. Antibiotic treatment reversed this effect. The inactivation of Kupffer cells or the replenishment with gadolinium chlorine reduced proinflammatory cytokine production and reversed declines in DSB repair. The addition of proinflammatory cytokines ablated DSBs joining mediated by macrophage derived heparin binding epidermal-growth factor-like-growth factor.
Source:
https://gut.bmj.com/content/early/2019/10/05/gutjnl-2019-318491.abstract
