Immune gene regulation is associated with age and environmental adversity in a nonhuman primate.

Phenotypic aging is ubiquitous across mammalian species, suggesting shared underlying mechanisms of aging. Aging is linked to molecular changes to DNA methylation and gene expression, and environmental factors, such as severe external challenges or adversities, can moderate these age-related changes. Yet, it remains unclear whether environmental adversities affect gene regulation via the same molecular pathways as chronological, or 'primary', aging. Investigating molecular aging in naturalistic animal populations can fill this gap by providing insight into shared molecular mechanisms of aging and the effects of a greater diversity of environmental adversities - particularly those that can be challenging to study in humans or laboratory organisms. Here, we characterised molecular aging - specifically, CpG methylation - in a sample of free-ranging rhesus macaques living off the coast of Puerto Rico (n samples = 571, n individuals = 499), which endured a major hurricane during our study. Age was associated with methylation at 78,661 sites (31% of all sites tested). Age-associated hypermethylation occurred more frequently in areas of active gene regulation, while hypomethylation was enriched in regions that show less activity in immune cells, suggesting these regions may become de-repressed in older individuals. Age-associated hypomethylation also co-occurred with increased chromatin accessibility while hypermethylation showed the opposite trend, hinting at a coordinated, multi-level loss of epigenetic stability during aging. We detected 32,048 CpG sites significantly associated with exposure to a hurricane, and these sites overlapped age-associated sites, most strongly in regulatory regions and most weakly in quiescent regions. Together, our results suggest that environmental adversity may contribute to aging-related molecular phenotypes in regions of active gene transcription, but that primary aging has specific signatures in non-regulatory regions.

The biology of aging in a social world: Insights from free-ranging rhesus macaques.

Social adversity can increase the age-associated risk of disease and death, yet the biological mechanisms that link social adversities to aging remain poorly understood. Long-term naturalistic studies of nonhuman animals are crucial for integrating observations of social behavior throughout an individual's life with detailed anatomical, physiological, and molecular measurements. Here, we synthesize the body of research from one such naturalistic study system, Cayo Santiago, which is home to the world's longest continuously monitored free-ranging population of rhesus macaques (Macaca mulatta). We review recent studies of age-related variation in morphology, gene regulation, microbiome composition, and immune function. We also discuss ecological and social modifiers of age-markers in this population. In particular, we summarize how a major natural disaster, Hurricane Maria, affected rhesus macaque physiology and social structure and highlight the context-dependent and domain-specific nature of aging modifiers. Finally, we conclude by providing directions for future study, on Cayo Santiago and elsewhere, that will further our understanding of aging across different domains and how social adversity modifies aging processes.

Evolution of vertebral numbers in primates, with a focus on hominoids and the last common ancestor of hominins and panins.

The primate vertebral column has been extensively studied, with a particular focus on hominoid primates and the last common ancestor of humans and chimpanzees. The number of vertebrae in hominoids-up to and including the last common ancestor of humans and chimpanzees-is subject to considerable debate. However, few formal ancestral state reconstructions exist, and none include a broad sample of primates or account for the correlated evolution of the vertebral column. Here, we conduct an ancestral state reconstruction using a model of evolution that accounts for both homeotic (changes of one type of vertebra to another) and meristic (addition or loss of a vertebra) changes. Our results suggest that ancestral primates were characterized by 29 precaudal vertebrae, with the most common formula being seven cervical, 13 thoracic, six lumbar, and three sacral vertebrae. Extant hominoids evolved tail loss and a reduced lumbar column via sacralization (homeotic transition at the last lumbar vertebra). Our results also indicate that the ancestral hylobatid had seven cervical, 13 thoracic, five lumbar, and four sacral vertebrae, and the ancestral hominid had seven cervical, 13 thoracic, four lumbar, and five sacral vertebrae. The last common ancestor of humans and chimpanzees likely either retained this ancestral hominid formula or was characterized by an additional sacral vertebra, possibly acquired through a homeotic shift at the sacrococcygeal border. Our results support the 'short-back' model of hominin vertebral evolution, which postulates that hominins evolved from an ancestor with an African ape-like numerical composition of the vertebral column.

The biology of aging in a social world:insights from free-ranging rhesus macaques.

Social adversity can increase the age-associated risk of disease and death, yet the biological mechanisms that link social adversities to aging remain poorly understood. Long-term naturalistic studies of nonhuman animals are crucial for integrating observations of social behavior throughout an individual's life with detailed anatomical, physiological, and molecular measurements. Here, we synthesize the body of research from one such naturalistic study system, Cayo Santiago Island, which is home to the world's longest continuously monitored free-ranging population of rhesus macaques. We review recent studies of age-related variation in morphology, gene regulation, microbiome composition, and immune function. We also discuss ecological and social modifiers of age-markers in this population. In particular, we summarize how a major natural disaster, Hurricane Maria, affected rhesus macaque physiology and social structure and highlight the context-dependent and domain-specific nature of aging modifiers. Finally, we conclude by providing directions for future study, on Cayo Santiago and elsewhere, that will further our understanding of aging across different domains and how social adversity modifies aging processes.