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

跨多个领域的老龄化速度的社会修饰者 随着老龄化人口的快速增长，老龄化的发生率也相应快速增加-- 相关疾病。然而，并不是每个人都同时成为与衰老相关的疾病的受害者--确实存在 老年病的发病和进展的年龄有很大的变异性。有证据表明， 这种差异与社会逆境有关，如社会经济地位低下和社会孤立。但 确切地说，社会逆境是如何“深入”改变老龄化速度的，目前仍不得而知。这方面的进展 排名靠前是因为要求提供个人已实现生物年龄的全面肖像 在多个领域和器官系统中的寿命，这一壮举在人类身上基本上是不可行的。一个合适的动物模型， 这种非人类的灵长类动物是需要的，因为社会行为和衰老的自然变化都是 与人类同源，并可在不同组织和区域追踪其寿命。 衰老。 这项建议的目标是建立一个生物学模型，说明社会对自然老龄化的贡献。 非人灵长类动物的数量。为了做到这一点，它利用了对自由生活的恒河猴种群的长期研究 猕猴。这些动物为探索衰老及其社会决定因素提供了一个无与伦比的机会 大量的种群生活在自然主义的环境中，因为他们与人类在进化上很接近， 社会逆境的同源自然标志，包括社会孤立和低社会地位，由 优势等级低，寿命相当短(3-4倍)。这个项目测试了这样一个假设，即社会 逆境加速了多种组织类型和三个中心衰老领域的生物衰老：(I) 分子(例如DNA甲基化和端粒磨损)、(Ii)免疫学(例如炎症和白细胞 构成)，以及(Iii)身体(例如，脆弱，包括关节活动和身体状况)。 该项目的目标1旨在通过以下方式生成跨域和系统的全面老化配置文件 这一方法是：(A)横截面跨组织类型和(B)纵向跨个体寿命。通过 跟踪不同组织类型和寿命的衰老，我们将准确定位衰老变化的可修改来源，如 并确定可改变的衰老区域的时间和性别特异性。目标2借鉴了详细的社交网络 测试社会逆境如何以及在哪些领域加速衰老的表型。 这个项目将对衰老生物学中的两个主要问题提供变革性的见解。首先，它将产生 使用自然灵长类动物模型研究衰老的分子、免疫学和物理特征的有价值的数据 对人类衰老有好处。其次，它将揭示社会环境如何改变老龄化的速度，这将告诉我们 有针对性地开展可减轻老龄化负担的社会和生理干预措施-- 我们老龄化人口中的相关疾病。

Social modifiers of the pace of aging across multiple domains 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.