Maintaining a favorable and stable social environment is crucial as people get older. One of the essential components of healthy aging, for instance, has been recognized as maintaining close relationships with friends and family.
Studies have demonstrated that while some physiological, mental, and physical impairments are unavoidable as people age, others can be avoided by preserving a healthy social environment.
Researchers have long been curious about these underlying causes and how the environment might offer a way to slow down the rate at which our brains deteriorate.
Many recent studies have indicated changes at the level of gene regulation, or how our genes are turned on and off, according to Noah Snyder-Mackler, an assistant professor at Arizona State University’s School of Life Sciences, the Center for Evolution and Medicine, and an affiliate of the Neurodegenerative Disease Research Center at ASU’s Biodesign Institute. “We still don’t have a good handle on how our social environment can “get under the skin” to affect our bodies and brains, but a lot of recent work has
And with the aid of modern technologies, researchers can start to unravel the puzzling relationship between the dynamics of one’s social surroundings and molecular alterations in the brain.
In order to better understand how our social environment can affect our physiology, from the organismal level all the way down to our genes, scientists like Snyder-Mackler have turned to using nonhuman primates, our closest genetic relatives. This is due to the difficulty of conducting human studies and the fact that aging processes last for decades of the average human life span.
Now, Snyder-Mackler heads an international research team for a new study with co-first authors Kenneth Chiou (a postdoctoral researcher at ASU) and Alex DeCasien (previously at New York University, currently a postdoctoral researcher at the National Institute of Mental Health).
It showed a link between the social environment and healthy brains in a population of macaque monkeys by showing that females with higher social rank had younger, more resilient molecular profiles.
Rhesus macaques, “the best-studied nonhuman monkey model species in medicine,” were used for this experiment. The reduction in bone density and muscle mass, alterations to the immune system, and a general decline in behavioral, sensory, and cognitive function are all age-related changes that these animals also exhibit, according to Snyder-Mackler.
The team included important partners from the University of Washington, the University of Pennsylvania, the University of Exeter, New York University, North Carolina Central University, the University of Calgary, and the University of Lyon. It also included key collaborators from the Caribbean Primate Research Center/University of Puerto Rico. The National Institute on Aging, National Institute of Mental Health, National Science Foundation, and the National Institutes of Health Office of Research Infrastructure Programs provided funding for the study, which was published in the journal Nature Neuroscience.
Professor Michael Platt of the Perelman School of Medicine, School of Arts and Sciences, and Wharton Business School at the University of Pennsylvania said, “This study builds upon more than 15 years of research by our team into the interactions between social behavior, genetics, and the brain in the Cayo macaques.” The results of our team’s research “show the value of all the effort and money put into this lengthy investigation.”
James Higham, an anthropology professor at New York University, said that the study “shows the benefit of developing long-term collaborative networks across institutions.” The secret to achieving significant transdisciplinary findings in naturalistic animal populations is long-term support for such networks.
The social environment and biology of aging
The investigation of the underlying causes and effects of variation in the social environment, at sizes ranging from minuscule molecules to the entire organism, is a major focus of Snyder’s work. Mackler’s
Research on this dynamic interplay between the environment and the genome has been accelerated in the last ten years by the development of new genomic technologies. Can adversity on a social or environmental level resemble aging on a biochemical level? “Definitely yes,” is the response. One of the first studies demonstrating that people who encountered a natural disaster, specifically a storm, had molecularly older immune systems was just recently published by Snyder and Mackler (10.1073/pnas.2121663119).
Rhesus macaques living in the wild on the remote island of Cayo Santiago, Puerto Rico, are the subject of their study. The Caribbean Primate Research Center has been caring for the primates on the island since 1938. (CPRC).
The team conducted two complementary studies to investigate the relationships between social status and the functioning of the brain: 1) creating extensive gene expression datasets from 15 different brain regions; and 2) concentrating on one region in greater detail at the single cell level (in this case, a detailed analysis within a single region of the brain, the dorsolateral prefrontal cortex (dlPFC), a brain area long associated with memory, planning, and decision-making). Along with this research, 36 study animals were used for in-depth behavioral observations and data collection (20 female and 16 male).
Emergent patterns
Eight different gene clusters popped out when they divided each sampled brain region by age. Those involved in metabolic processes, cell signaling, and the immunological and stress responses were among the most fascinating.
We discovered hundreds of genes with age-related variations in gene expression patterns, including about 1,000 with very consistent patterns throughout the brain, according to Chiou.
They then focused their investigation on enlarging the prefrontal cortex region of the brain down to the level of a single cell.
According to Chiou, “We added assessments of the expression of genes in 71,863 unique cells in the dlPFC across 24 females spanning the macaque lifespan to our brain-wide gene expression data.”
They were able to divide each individual cell in the dlPFC brain region into 26 different cell types and subtypes using the gene expression data after first classifying each cell into one of eight general classes of neural cells (excitatory neurons, microglia, etc.).
They also showed clear similarities between the age-related gene expression profiles of macaques and humans. While some of this variation was exclusive to areas of the brain linked to degenerative neurological disorders, other parts of the variation throughout the entire brain reflected preserved neuronal processes linked to aging.
When compared to data from the mouse and human brains, pathways essential for brain cell-to-cell communication (chemical synaptic transmission, shared across five regions), brain growth (negative regulation of neurogenesis, shared among three regions), and a crucial brain regulatory gene for cell growth and death showed the greatest similarities in variation linked to age across regions (positive regulation of the proinflammatory cytokine tumor necrosis factor, shared across three regions).
However, not all of the findings showed similarities in humans, indicating that there may be underlying factors in some neurodegenerative diseases that are also distinctively human.
These crucial distinctions between human and macaque aging processes may shed light on the peculiar mechanisms behind some human neurodegenerative illnesses.
Energy pathways (electron transport chain and oxidative phosphorylation, present in four locations) were among the metabolic processes that showed the greatest age divergence among regions. Interestingly, several of the most divergent gene sets between humans and monkeys were linked to human neurological illnesses like Parkinson’s disease (four locations), Huntington’s disease (three regions), and Alzheimer’s disease (one region).
According to DeCasien, “this suggests that, despite some differences between human and macaque neurodegeneration pathways in terms of age profiles, they still exhibit strong overlap with social adversity, paralleling epidemiological links in humans between social adversity and neurodegenerative diseases.”
Aging is associated with variation in the social environment
The scientists then used their data to examine the social elements of macaque aging, which have a number of distinctive characteristics. The dominance rank (the primate equivalent of social standing) of female macaques is passed down from their mothers and, for the most part, is constant throughout their lifetimes. Male macaques exhibit a quite different pattern, leaving their original groups when they reach adulthood and joining new ones at the bottom of the hierarchy before moving up as their time in the new group lengthens.
According to Snyder-Mackler, “Evidence in humans and other social mammals implies that diversity in social hardship is explained in part by variability in the risk, start, and course of age-related morbidities.” Low social status is linked to higher mortality in female macaques, for instance, and its effects on immune cell gene expression are comparable to human aging gene expression profiles.
They then sought to see if social adversity could be connected to the molecular markers of aging in the macaque brain. They discovered that the effect of rank on gene expression was primarily driven by younger molecular profiles in high-ranking females. This finding suggests that associations between higher rank and younger brain age are not expressed linearly along the social hierarchy but are instead unique to females with the highest ranks. High social standing may come with a number of benefits, such as easier access to resources, more stable surroundings, and less peer pressure.
According to DeCasien, “Our findings offer some of the first evidence of molecular similarities between aging and social adversity in the brain, providing a key mechanism linking unfavorable (or, conversely, beneficial) environments and the earlier onset and faster progression of age-related brain decline and disease.”
Final thoughts
These atlases and discoveries now offer useful research targets in a practical, therapeutically significant model of human health and aging.
These connections may have a cause; for instance, it has been suggested that the ongoing stress of social hardship speeds up aging by encouraging chronic inflammation brought on by a compromised immune system. Their work highlights the significance of taking the social environment into account as a significant moderator of aging and health.
According to Lauren Brent, an associate professor of psychology and animal behavior at the University of Exeter, “There is no longer any doubt that the social lives of humans and other group-living animals are inextricably connected with the rest of their biology.” Exciting new studies will explain why social interactions may affect how rapidly we age and if these effects are reversible.
And based on the information and conclusions from this study, we might already be close to achieving this aim. Snyder-Mackler stated that when taken as a whole, her team’s findings “offer a rich scientific resource for recording age-associated chemical changes in the brain of a model nonhuman monkey living in a complex social and naturalistic setting.” We anticipate that they will provide fresh perspectives on how we can all live longer, healthier, and happier lives.
