Social relationships and physiological determinants of longevity across the human life span.
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ABSTRACT:
SUBMITTER: Yang YC
PROVIDER: S-EPMC4725506 | biostudies-other | 2016 Jan
REPOSITORIES: biostudies-other
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Project description:ObjectivesAlthough stronger social relationships have been associated with reduced mortality risk in prior research, their associations with favorable health outcomes are understudied. We evaluated whether higher social integration levels were associated with longer life span and greater likelihood of achieving exceptional longevity.MethodWomen from the Nurses' Health Study completed the Berkman-Syme Social Network Index in 1992 (N = 72,322; average age = 58.80 years), and were followed through 2014 with biennial questionnaires. Deaths were ascertained from participants' families, postal authorities, and death registries. Accelerated failure time models adjusting for relevant covariates estimated percent changes in life span associated with social integration levels; logistic regressions evaluated likelihood of surviving to age 85 years or older among women who could reach that age during follow-up (N = 16,818).ResultsAfter controlling for baseline demographics and chronic diseases, socially integrated versus isolated women had 10% (95% confidence interval [CI] = 8.80-11.42) longer life span and 41% (95% CI = 1.28-1.54) higher odds of surviving to age 85 years. All findings remained statistically significant after further adjusting for health behaviors and depression.DiscussionBetter social integration is related to longer life span and greater likelihood of achieving exceptional longevity among midlife women. Findings suggest social integration may be an important psychosocial asset to evaluate for promoting longer, healthier lives.
| S-EPMC7664314 | biostudies-literature
Project description:The selective impact of pathogen epidemics on host defenses can be strong but remains transient. By contrast, life-history shifts can durably and continuously modify the balance between costs and benefits, which arbitrates the evolution of host defenses. Their impact, however, has seldom been documented. Here, we show with a simple mathematical model that the selective advantage of the defense system is expected to decrease with decreasing life span. We further document that, in natural populations of the model plant system Arabidopsis thaliana, the expression level of defense genes correlate positively with flowering time, a proxy for the length of vegetative life span. Using a genetic strategy to partition life span-dependent and –independent defense genes, we demonstrate that this positive co-variation is not explained by the pleiotropic action of major regulatory genes controlling both defense and life span. In agreement with our model, this study reveals that natural selection has likely assembled alleles promoting lower expression of defense genes with alleles decreasing the duration of vegetative life span in natural populations of A. thaliana. This is the first study demonstrating that life history evolution has a pervasive impact on the evolution of host immunity.
2017-05-31 | GSE97664 | GEO
Project description:Humans in strong social relationships are more likely to live longer because social relationships may buffer stressors and thus have protective effects. However, a shortcoming of human studies is that they often rely on self-reporting of these relationships. By contrast, observational studies of non-human animals permit detailed analyses of the specific nature of social relationships. Thus, discoveries that some social animals live longer and healthier lives if they are involved in social grooming, forage together or have more affiliative associates emphasizes the potential importance of social relationships on health and longevity. Previous studies have focused on the impact of social metrics on longevity in obligately social species. However, if sociality indeed has a key role in longevity, we might expect that affiliative relationships should also influence longevity in less social species. We focused on socially flexible yellow-bellied marmots (Marmota flaviventer) and asked whether female longevity covaries with the specific nature of social relationships. We quantified social relationships with social network statistics that were based on affiliative interactions, and then estimated the correlation between longevity and sociality using bivariate models. We found a significant negative phenotypic correlation between affiliative social relationship strength and longevity; marmots with greater degree, closeness and those with a greater negative average shortest path length died at younger ages. We conclude that sociality plays an important role in longevity, but how it does so may depend on whether a species is obligately or facultatively social.
| S-EPMC5805924 | biostudies-literature
Project description:The functional connectome of the human brain represents the fundamental network architecture of functional interdependence in brain activity, but its normative growth trajectory across the life course remains unknown. Here, we aggregate the largest, quality-controlled multimodal neuroimaging dataset from 119 global sites, including 33,809 task-free fMRI and structural MRI scans from 32,328 individuals ranging in age from 32 postmenstrual weeks to 80 years. Lifespan growth charts of the connectome are quantified at the whole cortex, system, and regional levels using generalized additive models for location, scale, and shape. We report critical inflection points in the non-linear growth trajectories of the whole-brain functional connectome, particularly peaking in the fourth decade of life. Having established the first fine-grained, lifespan-spanning suite of system-level brain atlases, we generate person-specific parcellation maps and further show distinct maturation timelines for functional segregation within different subsystems. We identify a spatiotemporal gradient axis that governs the life-course growth of regional connectivity, transitioning from primary sensory cortices to higher-order association regions. Using the connectome-based normative model, we demonstrate substantial individual heterogeneities at the network level in patients with autism spectrum disorder and patients with major depressive disorder. Our findings shed light on the life-course evolution of the functional connectome and serve as a normative reference for quantifying individual variation in patients with neurological and psychiatric disorders.
| S-EPMC10515818 | biostudies-literature
Project description:While average human life expectancy has increased dramatically in the last century, the maximum life span has only modestly increased. These observations prompted the notion that human life span might have reached its maximal natural limit of ~115 years. To evaluate this hypothesis, we conducted a systematic analysis of all-cause human mortality throughout the 20th century. Our analyses revealed that, once cause of death is accounted for, there is a proportional increase in both median age of death and maximum life span. To examine whether pathway targeted aging interventions affected both median and maximum life span, we analyzed hundreds of interventions performed in multiple organisms (yeast, worms, flies, and rodents). Three criteria: median, maximum, and last survivor life spans were all significantly extended, and to a similar extent. Altogether, these findings suggest that targeting the biological/genetic causes of aging can allow breaking the currently observed ceiling of human maximal life span.
| S-EPMC6454488 | biostudies-literature
Project description:BackgroundLoneliness and social isolation are emerging public health challenges for aging populations.MethodsWe followed N = 11 302 U.S. Health and Retirement Study participants aged 50-95 from 2006 to 2014 to measure persistence of experiences of loneliness and exposure to social isolation. We tested associations of longitudinal loneliness and social isolation phenotypes with disability, morbidity, mortality, and biological aging through 2018.ResultsDuring follow-up, 18% of older adults met criteria for loneliness, with 6% meeting criteria at 2 or more follow-up assessments. For social isolation, these fractions were 21% and 8%. Health and Retirement Study participants who experienced loneliness and were exposed to social isolation were at increased risk for disease, disability, and mortality. Those experiencing persistent loneliness were at a 57% increased hazard of mortality compared to those who never experienced loneliness. For social isolation, the increase was 28%. Effect sizes were somewhat larger for counts of prevalent activity limitations and somewhat smaller for counts of prevalent chronic diseases. Covariate adjustment for socioeconomic and psychological risks attenuated but did not fully explain associations. Older adults who experienced loneliness and were exposed to social isolation also exhibited physiological indications of advanced biological aging (Cohen's d for persistent loneliness and social isolation = 0.26 and 0.21, respectively). For loneliness, but not social isolation, persistence was associated with increased risk.ConclusionsDeficits in social connectedness prevalent in a national sample of U.S. older adults were associated with morbidity, disability, and mortality and with more advanced biological aging. Bolstering social connectedness to interrupt experiences of loneliness may promote healthy aging.
| S-EPMC8514074 | biostudies-literature
Project description:Chemosensation is a potent modulator of organismal physiology and longevity. In Drosophila, loss of recognition of diverse tastants has significant and bidirectional life-span effects. Recently published results revealed that when flies were unable to taste water, they increased its internal generation, which may have subsequently altered life span. To determine whether similar adaptive responses occur in other contexts, we explored the impact of sensory deficiency of other metabolically important molecules. Trehalose is a major circulating carbohydrate in the fly that is recognized by the gustatory receptor Gr5a. Gr5a mutant flies are short lived, and we found that they specifically increased whole-body and circulating levels of trehalose, but not other carbohydrates, likely through upregulation of de novo synthesis. dILP2 transcript levels were increased in Gr5a mutants, a possible response intended to reduce hypertrehalosemia, and likely a contributing factor to their reduced life span. Together, these data suggest that compensatory physiological responses to perceived environmental scarcity, which are designed to alleviate the ostensive shortage, may be a common outcome of sensory manipulation. We suggest that future investigations into the mechanisms underlying sensory modulation of aging may benefit by focusing on direct or indirect consequences of physiological changes that are designed to correct perceived disparity with the environment.
| S-EPMC4598796 | biostudies-literature
Project description:Background: Improving maternal health in Ethiopia is a major public health challenge. International studies indicate that it is possible to improve maternal health outcomes through action on the Social Determinants of Health (SDH). This study aimed to explore the SDH that influence the antenatal care (ANC) utilization in Ethiopia over time. Methods: The study used data from the nation-wide surveys conducted by the Ethiopian Central Statistical Agency (CSA) and ORC Macro International, USA in 2005, 2011, and 2016. A negative binomial with random effects at cluster level was used to model the number of ANC visits whereas a multilevel binary logistic regression modeled binary responses relating to whether a woman had at least 4 ANC visits or not. The model estimates were obtained with the statistical software Stata SE 15 using the restricted maximum likelihood method. Results: Although the median number of ANC visits significantly increased between 2005 and 2016, the majority of the women do not obtain the four ANC visits during pregnancy as recommended. The odds of having at least four ANC visits were significantly lower among women: below 20 years, those living in the rural areas, having higher birth order, or Muslim. In contrast, higher educational attainment, higher socio-economic status, exposure to mass media, and self-reporting decision empowerment were significantly associated with having at least four ANC visits. Conclusion: The use of ANC visits is driven mostly by the social determinants of health rather than individual health risk. The importance of the various SDHs needs to be recognized by Ministry of Health policy and program managers as a key driving force behind the country's challenges with reaching targets in the health agenda related to maternal health, particularly related to the recommended number of ANC visits.
| S-EPMC6603173 | biostudies-literature
Project description:ABSTRACT MAGWIRE, MICHAEL MAHLON. Mutations Increasing Drosophila melanogaster Life Span. (Under the direction of Trudy F. C. Mackay.) Better living conditions and advances in medicine have made it possible for humans to live considerably longer than before. This has uncovered many health problems associated with age. By identifying genes involved in the limitation of life span, we may better understand the processes that lead to aging. In model organisms, we can use mutagenesis to discover mutations that increase life span, and hence infer that the wild-type allele limits life span by some means. We have assessed longevity in a collection of 1332 co-isogenic gene-trap P-element insertion lines and determined changes in life span of each insert line relative to the corresponding control line. Significant lines were determined via two different methods of analysis: A 95% confidence interval was established based on deviations of the mutant life spans from the controls and Dunnett’s two tailed t-tests were used to examine differences between mutant and control in each individual block. Based on the 95% confidence interval, 139 inserts displayed an increase in life span and 194 inserts a decrease. Using Dunnett’s, 70 lines increased in life span, while 270 decreased in life span. An additional 48 increased longevity lines were close enough to meeting Dunnett’s criteria to be considered for additional investigation. Combining these two analyses, we chose 83 inserts associated with increased life span for a secondary screen using an additional twelve replicates. 58 of these lines remained significant. We have determined the P-element insertion site for 50 of these lines. Starvation resistance, chill coma recovery time and climbing activity were measured on the lines remaining significant after the the secondary screen to identify pleiotropic effects. A positive correlation was found for males between life span and starvation resistance as well as between life span and chill coma recovery. Females only displayed a correlation between life span and chill coma recovery, which was negative. None of the lines indicated increased fitness for all phenotypes, indicating there may be some type of trade-off. There also appears to be a lot of pleiotropic variation depending on background and sex. Ten of the lines, all with the same parental background, were chosen for a half-diallel cross to identify epistasis between the mutants. There were substantial epistatic interactions between all ten lines. Furthermore, males and females displayed vastly different patterns of epistasis, again indicating major differences in life span regulation between the sexes. Finally, a subset of seven of the lines used in the epistatic study, in addition to the corresponding parental control, were chosen for microarray analysis to look for possible pathways and novel genes involved in increasing life span. 1,996 probe sets were significant at a false discovery rate q-value threshold of q < 0.0001. Tukeys tests were carried out for these probe sets to determine how each of the seven mutant backgrounds differed compared to the control and each other. In addition, each mutant background was compared individually with the control to identify any changes in expression. Gene ontologies were determined for each of the lines to identify over-represented biological functions which would indicate possible longevity pathways. Dozens of pathways were suggested, including several novel pathways. Keywords: Genetic (P-element insertion) modification and comparison to control line
2008-08-01 | GSE8775 | GEO
Project description:Advanced age is not only a major risk factor for a range of disorders within an aging individual but may also enhance susceptibility for disease in the next generation. In humans, advanced paternal age has been associated with increased risk for a number of diseases. Experiments in rodent models have provided initial evidence that paternal age can influence behavioral traits in offspring animals, but the overall scope and extent of paternal age effects on health and disease across the life span remain underexplored. Here, we report that old father offspring mice showed a reduced life span and an exacerbated development of aging traits compared with young father offspring mice. Genome-wide epigenetic analyses of sperm from aging males and old father offspring tissue identified differentially methylated promoters, enriched for genes involved in the regulation of evolutionarily conserved longevity pathways. Gene expression analyses, biochemical experiments, and functional studies revealed evidence for an overactive mTORC1 signaling pathway in old father offspring mice. Pharmacological mTOR inhibition during the course of normal aging ameliorated many of the aging traits that were exacerbated in old father offspring mice. These findings raise the possibility that inherited alterations in longevity pathways contribute to intergenerational effects of aging in old father offspring mice.
| S-EPMC5877957 | biostudies-literature