Social modifiers of the pace of aging across multiple domains and tissues

Social modifiers of the pace of aging across multiple domains and tissues Social modifiers of the pace of aging across multiple domains and tissues With a rapidly growing aging population comes a correspondingly rapid increase in the incidence of aging-related diseases. However, not everyone falls victim to aging-related diseases at the same time there is substantial variability in the age at onset and progression of diseases of aging. Evidence suggests that part of this variation is associated with social adversity, such as low socioeconomic status and social isolation. But precisely how social adversity gets under the skin to alter the pace of aging remains elusive. Progress on this front lags because comprehensive portraits of individuals realized biological age are required across the lifespan in multiple domains and organ systems, a feat largely unfeasible in humans. A suitable animal model, such a non-human primate, is needed where natural variation in both social behavior and aging are homologous to that in humans, and can be tracked across the lifespan in different tissues and domains of aging. The objective of this proposal is to develop a biological model of the social contributions to aging in a natural population of nonhuman primates. To do so, it draws on a long-term study of a free-living population of rhesus macaques. These animals present an unparalleled opportunity to probe aging and its social determinants in a large population living in naturalistic circumstances because of their phylogenetic proximity to humans, homologous natural markers of social adversity, including social isolation and low social status represented by low dominance rank, and considerably shorter (3-4x) lifespans. This project tests the hypothesis that social adversity accelerates biological aging across multiple tissue types and in three central aging domains: (i) molecular (e.g., DNA methylation and telomere attrition), (ii) immunological (e.g., inflammation and leukocyte composition), and (iii) physical (e.g., frailty, including joint mobility and body condition). Aim 1 of this project aims to generate comprehensive aging profiles across domains and systems by taking an approach that is: (a) cross-sectional across tissue types and (b) longitudinal over individuals lifespans. By tracking aging across tissue types and the lifespan, we will pinpoint modifiable sources of aging variation, as well as establish the timing and sex-specificity of modifiable aging domains. Aim 2 draws on detailed social phenotypes to test how, and in what domains, social adversity accelerates aging. This project will lend transformative insights into two major issues in the biology of aging. First, it will generate valuable data on molecular, immunological and physical signatures of aging using a naturalistic primate model for human aging. Second, it will reveal how the social environment alters the pace of aging, which will inform the targeted development of social and physiological interventions that could reduce the burden of aging-related disease in our aging population. Social modifiers of the pace of aging across multiple domains and tissues The size of the elderly population in the United States is increasing rapidly. As individuals age, their mobility is impacted through the development of degenerative joint disease (DJD), reducing their ability to interact with both the social and physical aspects of the world, so reducing quality of life. This supplement adds new measures of skeletal health to the parent proposal, which tracks naturalistic molecular and immunological changes in a nonhuman primate model across the lifespan. The specific objective of the supplement is to probe the relationship between aging signatures in the genome across tissues, immune function and inflammation, and the onset of age-related bone diseases, in order to assess the potential for biomarkers of DJD that can be measured before the onset of physical symptoms. As part of this project, a permanent digital archive will be created to preserve skeletons of rhesus macaques who are being studied for the parent proposal, and to promote external research access to that collection. In addition to providing a comprehensive and highly-novel dataset on the etiology of age-related skeletal diseases in a non-human primate model, it will also be key to the career development of a post-doctoral researcher from an underrepresented background, who will expand on their current skillset by learning immunoassay and molecular techniques, and by exploring new avenues of inquiry in skeletal health and aging biology. Social modifiers of the pace of aging across multiple domains and tissues With a rapidly growing aging population comes a correspondingly rapid increase in the incidence of aging-related diseases. However, not everyone falls victim to aging-related diseases at the same time there is substantial variability in the age at onset and progression of diseases of aging. Evidence suggests that part of this variation is associated with social adversity, such as low socioeconomic status and social isolation. But precisely how social adversity gets under the skin to alter the pace of aging remains elusive. Progress on this front lags because comprehensive portraits of individuals realized biological age are required across the lifespan in multiple domains and organ systems, a feat largely unfeasible in humans. A suitable animal model, such a non-human primate, is needed where natural variation in both social behavior and aging are homologous to that in humans, and can be tracked across the lifespan in different tissues and domains of aging. The objective of this proposal is to develop a biological model of the social contributions to aging in a natural population of nonhuman primates. To do so, it draws on a long-term study of a free-living population of rhesus macaques. These animals present an unparalleled opportunity to probe aging and its social determinants in a large population living in naturalistic circumstances because of their phylogenetic proximity to humans, homologous natural markers of social adversity, including social isolation and low social status represented by low dominance rank, and considerably shorter (3-4x) lifespans. This project tests the hypothesis that social adversity accelerates biological aging across multiple tissue types and in three central aging domains: (i) molecular (e.g., DNA methylation and telomere attrition), (ii) immunological (e.g., inflammation and leukocyte composition), and (iii) physical (e.g., frailty, including joint mobility and body condition). Aim 1 of this project aims to generate comprehensive aging profiles across domains and systems by taking an approach that is: (a) cross-sectional across tissue types and (b) longitudinal over individuals lifespans. By tracking aging across tissue types and the lifespan, we will pinpoint modifiable sources of aging variation, as well as establish the timing and sex-specificity of modifiable aging domains. Aim 2 draws on detailed social phenotypes to test how, and in what domains, social adversity accelerates aging. This project will lend transformative insights into two major issues in the biology of aging. First, it will generate valuable data on molecular, immunological and physical signatures of aging using a naturalistic primate model for human aging. Second, it will reveal how the social environment alters the pace of aging, which will inform the targeted development of social and physiological interventions that could reduce the burden of aging-related disease in our aging population. Social modifiers of the pace of aging across multiple domains and tissues Social modifiers of the pace of aging across multiple domains and tissues