Upregulation of colonic luminal polyamines produced by intestinal microbiota delays senescence in mice

Prevention of quality of life (QOL) deterioration is associated with the inhibition of geriatric diseases and the regulation of brain function. However, no substance is known that prevents the aging of both body and brain. It is known that polyamine concentrations in somatic tissues (including the brain) decrease with increasing age, and polyamine-rich foods enhance longevity in yeast, worms, flies, and mice, and protect flies from age-induced memory impairment. A main source of exogenous polyamines is the intestinal lumen, where they are produced by intestinal bacteria. We found that arginine intake increased the concentration of putrescine in the colon and increased levels of spermidine and spermine in the blood. Mice orally administered with arginine in combination with the probiotic bifidobacteria LKM512 long-term showed suppressed inflammation, improved longevity, and protection from age-induced memory impairment. This study shows that intake of arginine and LKM512 may prevent aging-dependent declines in QOL via the upregulation of polyamines. P olyamines (PAs) such as putrescine (PUT), spermidine (SPD), and spermine (SPM) are present in the cells of all mammalian species. PAs have various bioactivities, such as the synthesis and stabilization of DNA, RNA and protein, and stimulation of cell proliferation or differentiation 1,2 . PAs also have strong antiinflammatory functions There is a close association between PAs and maintenance of intestinal mucosal barrier functions, which are required for the secretion of mucous or secretory IgA from intestinal epithelial cells 5 , recovery of damaged mucosal layers 6 , and upregulation of E-cadherin 7 and occluding proteins 8 that are bound by tight junctions to intestinal epithelial cells. Moreover, PAs suppress mutagenic events by repressing the occurrence of frameshift mutations 9 and DNA alkylation 10 . Recent studies demonstrated that PAs can enhance longevity in bacteria, yeast, worms, flies, and mice, and that this is due to promotion of autophagy(definition) 11 . In the case of mammals, Soda et al. extended the lifespan of mice by administering PA-rich food 12 . Consistent with this, we previously found that increasing intestinal PA concentrations by supplementing chow with Bifidobacterium animalis subsp. lactis LKM512 inhibited senescence(definition) and enhanced longevity in mice 13 . PAs also regulate brain function, which is one of the most important criteria upon which quality of life (QOL) is evaluated. N-methyl-D-aspartate (NMDA) receptors, which play a key role in activation-dependent synaptic plasticity and formation of memory in rodents, are regulated by PAs 14 . Chronic treatment with difluoromethylornithine (DFMO), a potent and irreversible inhibitor of ornithine decarboxylase (ODC), depletes PAs and impairs spatial learning and memory 15 . In contrast, striatal injection of SPM improved recognition memory Recently, it has been reported that PA-rich diets protect fruit flies from age-induced memory impairment