Pamela Larsen, Ph.D.

What biological mechanisms govern adult health and life span? Genetic and environment components contribute to a long healthy life. The longevity manipulations we use in C. elegans are: 1) mutation of the daf-2 gene, which is homologous to insulin/IGF1 signaling pathways, and 2) cultivation at a cool temperature. Both cooler core body temperatures and reduction of the daf-2/insulin/IGF-1 signaling pathway are pro-survival in multiple species including humans. We are defining environment by genotype interactions that alter gene transcription (epigenetics) and then testing the functional contribution to adult health and life span. For this our studies include different genotypes at different non-stress-inducing temperatures. We have found that health can be uncoupled from long life. Environmental changes trigger beneficial and detrimental responses. By associating molecular signatures with phenotypes, we can better predict adult health and life span outcomes in different genotypes and environments.

The figure shows results from a neurological exam we did on individuals each day from when they were healthy middle-aged adults. In wild type, we find locomotion slows with age and a small number become paralyzed when old. When we inhibit our candidate adaptive response, we see nearly all show progressive paralysis and yet the life span is not significantly shorter.