Bacteria-Host Interaction and Aging Mechanisms

We use the round worm, Caenorhabditis elegans as a model system to investigate how commensal bacteria affect the physiology and aging of their hosts.

Bacteria are not merely food for C. elegans. They colonize adult worms and can dramatically influence the animal’s behavior and life span. Similarly, billions of bacteria colonize the mammalian digestive tract, including that of the human. However, their effects on human wellbeing and lifespan remain largely unknown.

In the laboratory, C. elegans is fed almost exclusively on E. coli. However, in their natural habitat these nematodes consume soil bacteria, such as Bacilli. Remarkably, worms fed B. subtilis live twice as long as those fed E. coli. We identified several key metabolites produced by B. subtilis that extend the life span of the worm and render it more resistant to environmental stressors such as heat and oxidants.

We are designing probiotic strains of bacteria that significantly extend the nematode life span. We also investigate the mechanisms by which bacteria-derived small molecules increase nematode longevity. Separately, we study how different forms of commensal bacterial communities (e.g. biofilms) influence the nematode life span and resistance to stress and infection.

A model for bacterial NO signaling in C. elegans.. While in the worm’s intestine, vegetative B. subtilis produces NO. This small lipophilic molecule freely diffuses into C. elegans cells. There it induces a specific response that strictly depends on DAF-16 and HSF-1 activity and results in the induction of 65 genes, including hsps and several other cytoprotective genes (mtl-1, ctl-2, gei-7 and T19B10.2) (Gusarov et al., 2013) that have been implicated in longevity and stress resistance. A proposed NO activated pathway is indicated in red.