Social stress, epigenetics and immune function across bat lifespans

总结

Summary The overarching goal of this project is to determine how social stress, due either to differences in social status or lack of social integration, influences innate immunity over the lifespan of bats. Bats are proposed for study because of their extraordinary longevity and sociality. No other mammalian group exhibits comparable longevity relative to body size or variation in sociality. In addition, recent evidence indicates that some bats do not exhibit several hallmarks of aging and can modulate their immune response to tolerate high levels of virus exposure. The four species chosen for study are distantly related, include some of the longest-lived species from three different families, and have been the subject of long-term studies involving individually marked animals, which makes them uniquely suitable for an aging study. Aim 1 will use gene expression of mononuclear white blood cells after ex vivo stimulation with lipopolysaccharide (LPS) to quantify immune response in first year and old (i.e. greater than mean adult lifespan) individuals of both sexes to determine if there are sex differences in immunity over the lifespan. DNA methylation will be profiled using a microarray that assays conserved sites and then used to determine if there are sex differences in epigenetic aging and to identify genomic biomarkers of aging. Aim 2 will evaluate the effect of social status in males of the four species on both gene expression and DNA methylation. Male status will be determined either from physical defense of female groups during the mating season or from estimates of paternity. Aim 3 will assess the effect of social integration on annual change in gene expression and DNA methylation in two ways, one of which will utilize variation in female group composition in wild greater spear-nosed bats and the other will utilize social networks measured at different spatial and temporal scales using captive vampire bats, which have perhaps the most complex social system of any bat. The R61 phase of the project will address Aims 1 and 2 in greater spear-nosed bats. The R33 phase will expand the scope of Aims 1 and 2 to include three additional species and will address Aim 3. The R33 phase will also expand the scope of the DNA methylation profiling by using whole genome bisulfite sequencing to determine the extent to which sex-specific aging biomarkers in bats compare to those in humans across the genome. This multispecies approach has the potential to reveal unique adaptations that contribute to longevity and do not simply reflect differences between a bat and other mammals.