The soil Mycobacterium sp. promotes health and longevity through different bacteria-derived molecules in Caenorhabditis elegans

Commensal bacteria and their derivatives hold significant promise as therapeutic interventions to delay aging. However, with the diverse nature of the soil microbiome
and the long lifespan of mammalian models, the exploration of the influence of soil
bacteria and bacteria-derived molecules on host aging remains limited. We conducted
a lifespan screening in Caenorhabditis elegans using plant root bacterial collection. Our
screening identified 8 genera of bacterial isolates capable of extending lifespan, with
Mycobacterium sp. Root265 exhibits the most pronounced effect on lifespan extension. Biochemical analysis revealed two specific molecules derived from Root265, polysaccharides (PSs) and arabinogalactan peptidoglycan (AGP), responsible for lifespan
extension via daf-16-dependent and -independent pathways, respectively. Notably,
AGP exhibited a unique ability to enhance protein homeostasis effectively. Moreover,
polar lipids originating from Root265 were found to extend lifespan while mitigating age-related BAS-1 decline in neurons. Intriguingly, even brief exposures to these
bioactive compounds were sufficient to achieve the lifespan-promoting effects. We
found diverse beneficial bacteria and anti-aging active compounds from soil bacteria.
These findings highlight the potential of exploring bacterial derivatives as therapies
targeting aging without the constraints associated with direct microbial interventions.