Animals respond to caloric restriction by altering their life history strategies to promote enhanced lifespan and expansion of their reproductive window. Different regimens limiting food availability and/or food intake result in distinct downstream effects. This observation demonstrates the complexity of the interaction between nutrition and aging-related physiology. Our research focuses on systemic physiologic signaling emanating from the intestine that influences life history strategies. The intestine plays a critical role in nutrient uptake and removal, functioning in food digestion, nutrient absorption and waste removal. The intestine also affects animal physiology and behavior more broadly through the release of peptides and insulin-like molecules that act on distinct targets to influence metabolic, developmental and behavioral choices. We are investigating the effects of an intestinal disruption that appears to induce a severe caloric restriction phenotype. The mutation of an intestinal gap junction subunit, innexin-16 (
inx-16), results in poor intestinal cell-to-cell communication that alters a rhythmic calcium wave. This calcium wave evokes signaling that initiates the digestive motor program resulting in regular waste elimination, defecation. The
inx-16 mutant suffers several defecation defects resulting in severe constipation. We are analyzing additional phenotypes associated with poor nutrition.
inx-16 mutants exhibit extended lifespan, reduced body size, delayed development, and reproductive changes associated with long-lived mutants. The mutants have low overall brood sizes and remain reproductively active much longer than wild-types. Egg production is a limiting factor and vitellogenin levels are compromised. The
inx-16s' Oil Red O stained fat levels are markedly reduced. These factors lead us to propose that nutrient uptake is altered in the mutant. Since feeding rates, measured by pharyngeal pumping, are normal, poor nutrient absorption may be the root cause of the aging and reproductive changes. To further elucidate the effects of altering intestinal calcium waves we are comparing the
inx-16 mutant with a feeding mutant,
eat-2, and a di- and tri-peptide transporter mutant,
pept-1, via epistatic and other comparative assays. This work will provide valuable insight into links between intestinal cell-cell communication, nutrient uptake and longevity.