Aging

How individual neurons age, the cellular pathways that regulate this process, and the ultimate effects aging on neuronal function, are poorly understood. The regenerative potential or ability of a neuron to regrow after injury declines with age across many species and is variable between subtypes of neurons within a single organism. Understanding how the aging process is regulated across the nervous system could help to identify ways to restore and protect this critical tissue from age-related damage and decline.

The InsR/FOXO daf-2/daf-16 pathway is a well-established modulator of lifespan across many species. We found that daf-2/daf-16 regulates worm lifespan and neuronal regenerative lifespan, the ability of a neuron to regrow in older animals, independently of each other. This indicates that the mechanisms regulating the neuronal aging are separate and distinct from those that affect organismal lifespan (doi: 10.1016/j.neuron.2013.11.019).

Regenerative lifespan is variable between subtypes of neurons, some neurons regenerate in the adult animal while others do not.  By taking advantage of the fact that C. elegans have only 302 neurons, all of which have been transcriptionally profiled (doi.org/10.1101/737577), we are working to delineate the molecular mechanisms that account for this heterogeneity of neuronal aging within a single species.