Dataset Information

Multi-system physiological dysregulation and ageing in a subsistence population.

ABSTRACT: Humans have the longest post-reproductive lifespans and lowest rates of actuarial ageing among primates. Understanding the links between slow actuarial ageing and physiological change is critical for improving the human 'healthspan'. Physiological dysregulation may be a key feature of ageing in industrialized populations with high burdens of chronic 'diseases of civilization', but little is known about age trajectories of physiological condition in subsistence populations with limited access to public health infrastructure. To better characterize human physiological dysregulation, we examined age trajectories of 40 biomarkers spanning the immune (n = 13 biomarkers), cardiometabolic (n = 14), musculoskeletal (n = 6) and other (n = 7) systems among Tsimane forager-horticulturalists of the Bolivian Amazon using mixed cross-sectional and longitudinal data (n = 22 115 observations). We characterized age-related changes using a multi-system statistical index of physiological dysregulation (Mahalanobis distance; D_m) that increases with age in both humans and other primates. Although individual biomarkers showed varied age profiles, we found a robust increase in age-related dysregulation for Tsimane (β = 0.17-0.18) that was marginally faster than that reported for an industrialized Western sample (β = 0.14-0.16), but slower than that of other non-human primates. We found minimal sex differences in the pace or average level of dysregulation for Tsimane. Our findings highlight some conserved patterns of physiological dysregulation in humans, consistent with the notion that somatic ageing exhibits species-typical patterns, despite cross-cultural variation in environmental exposures, lifestyles and mortality. This article is part of the theme issue 'Evolution of the primate ageing process'.

SUBMITTER: Kraft TS

PROVIDER: S-EPMC7540955 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Energy-starved microbes in deep marine sediments subsist at near-zero growth for thousands of years, yet the mechanisms for their subsistence are unknown because no model strains have been cultivated from most of these groups. We investigated Baltic Sea sediments with single-cell genomics, metabolomics, metatranscriptomics, and enzyme assays to identify possible subsistence mechanisms employed by uncultured Atribacteria, Aminicenantes, Actinobacteria group OPB41, Aerophobetes, Chloroflexi, Deltaproteobacteria, Desulfatiglans, Bathyarchaeota, and Euryarchaeota marine group II lineages. Some functions appeared to be shared by multiple lineages, such as trehalose production and NAD+-consuming deacetylation, both of which have been shown to increase cellular life spans in other organisms by stabilizing proteins and nucleic acids, respectively. Other possible subsistence mechanisms differed between lineages, possibly providing them different physiological niches. Enzyme assays and transcripts suggested that Atribacteria and Actinobacteria group OPB41 catabolized sugars, whereas Aminicenantes and Atribacteria catabolized peptides. Metabolite and transcript data suggested that Atribacteria utilized allantoin, possibly as an energetic substrate or chemical protectant, and also possessed energy-efficient sodium pumps. Atribacteria single-cell amplified genomes (SAGs) recruited transcripts for full pathways for the production of all 20 canonical amino acids, and the gene for amino acid exporter YddG was one of their most highly transcribed genes, suggesting that they may benefit from metabolic interdependence with other cells. Subsistence of uncultured phyla in deep subsurface sediments may occur through shared strategies of using chemical protectants for biomolecular stabilization, but also by differentiating into physiological niches and metabolic interdependencies.IMPORTANCE Much of life on Earth exists in a very slow-growing state, with microbes from deeply buried marine sediments representing an extreme example. These environments are like natural laboratories that have run multi-thousand-year experiments that are impossible to perform in a laboratory. We borrowed some techniques that are commonly used in laboratory experiments and applied them to these natural samples to make hypotheses about how these microbes subsist for so long at low activity. We found that some methods for stabilizing proteins and nucleic acids might be used by many members of the community. We also found evidence for niche differentiation strategies, and possibly cross-feeding, suggesting that even though they are barely growing, complex ecological interactions continue to occur over ultralong timescales.

Project description:Research in the basic biology of ageing is increasingly identifying mechanisms and modifiers of ageing in short-lived organisms such as worms and mice. The ultimate goal of such work is to improve human health, particularly in the growing segment of the population surviving into old age. Thus far, few interventions have robustly transcended species boundaries in the laboratory, suggesting that changes in approach are needed to avoid costly failures in translational human research. In this review, we discuss both well-established and alternative model organisms for ageing research and outline how research in nonhuman primates is sorely needed, first, to translate findings from short-lived organisms to humans, and second, to understand key aspects of ageing that are unique to primate biology. We focus on rhesus macaques as a particularly promising model organism for ageing research owing to their social and physiological similarity to humans as well as the existence of key resources that have been developed for this species. As a case study, we compare gene regulatory signatures of ageing in the peripheral immune system between humans and rhesus macaques from a free-ranging study population in Cayo Santiago. We show that both mRNA expression and DNA methylation signatures of immune ageing are broadly shared between macaques and humans, indicating strong conservation of the trajectory of ageing in the immune system. We conclude with a review of key issues in the biology of ageing for which macaques and other nonhuman primates may uniquely contribute valuable insights, including the effects of social gradients on health and ageing. We anticipate that continuing research in rhesus macaques and other nonhuman primates will play a critical role in conjunction with the model organism and human biodemographic research in ultimately improving translational outcomes and extending health and longevity in our ageing population. This article is part of the theme issue 'Evolution of the primate ageing process'.

Dataset Information

Multi-system physiological dysregulation and ageing in a subsistence population.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets