Microbial evolutionary signatures of longevity in very old mice

Abstract

Aging, one of the biggest health challenges of our time, is associated with several occurrences, including an increase in inflammation and gut microbial dysbiosis. These events contribute to aging by rising intestinal permeability and inflammation, but it remains undisclosed how they influence microbiota evolution and pathobiont selection. Here we approach this question by comparing microbial evolution in the guts of mice of different ages: young (6-9 weeks old), old (19 months old), and very old (25 months old). Previous work described the adaptation of an E. coli commensal strain to the intestine of young animals and showed that it acquires metabolic-related mutations whereas, in old mice, the pattern is shifted towards stress-related mutations, and metabolic adaptations arise slower. Yet, we were interested in understanding the features associated with longevity, and for that, we compared frailty, intestinal inflammation, and microbiota composition of very old animals to younger ones. Very old mice had higher frailty but did not show higher intestinal inflammation than the old. Curiously, when compared with the other age groups, very old mice showed an increase in health-associated bacteria, e.g., Akkermansia muciniphila, and E. coli evolution resembled the pattern found in young animals, as it displayed more metabolic than stress-related mutations. These data suggest that microbiota alterations during aging may not be exclusively dysbiotic and may eventually even be associated with longevity.