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At least 19 recordsLinked to original sources

Life-course influence of birthweight and subsequent pathways on healthy aging: a Mendelian randomization study.

BACKGROUND: Birthweight readily measurable marker of fetal growth that may influence health across the lifespan. We aimed to investigate the potential causal association between birthweight and healthy aging and to identify the mediating roles of subsequent socioeconomic, behavioral, functional, and disease-related factors to inform life-course strategies to promote healthy aging and reduce health inequities. METHODS: We performed two-sample Mendelian randomization analyses in European-ancestry participants to estimate the effect of birthweight (n = 298,142-423,683) on two robust, composite healthy aging phenotypes (genetically independent phenotype of aging (aging-GIP) and multivariate aging-related genetic factor (mvAge)) and six individual aging phenotypes, including healthspan, resilience, parental lifespan, self-rated health, phenotypic age deceleration, and 90th percentile self-longevity (n = 34,710-1,958,774), and screened for 100 candidate mediators (n = 14,267-1,812,017) using a two-step mediation analysis. RESULTS: Genetically determined each 1-SD higher birthweight was associated with higher aging-GIP (β [95% CI] in different models ranging from 0.131 [0.066-0.196] to 0.162 [0.089-0.235] SDs) and mvAge (0.036 [0.010-0.063] to 0.045 [0.024-0.067]), independent of later-life obesity indicators; also with more interpretable benefits, including 12%-16% higher odds of longer healthspan, a 0.079-0.089 SD improvement in resilience, and a 1.22-1.74 year increase in parental lifespan. Of 100 candidates, 26 and 25 mediated the effect of birthweight on aging-GIP and mvAge, respectively, including socioeconomic indicators (education, household income, occupational attainment; individual mediation proportion: 12.72%-27.79%); behaviors (e.g., cheese intake, age at first sex; 10.38%-29.56%); physical functions (e.g., blood pressure, grip strength; 7.57%-42.65%); and cardiometabolic diseases (e.g., type 2 diabetes, cardiovascular diseases; 25.02%-70.11%). CONCLUSIONS: Higher birthweight within the normal range directly promotes healthy aging, mediated by multifaceted modifiable factors. Our findings advocate adopting a life-course approach to foster healthy aging, starting with optimal birthweight and extending to interventions that enhance socioeconomic status, promote healthy behaviors, strengthen physical functions, and prevent cardiometabolic diseases.

Mendelian Randomization Analysis

Bone mineral content of the healthy aged.

Using Norland-Cameron photon-absorption technique, bone mineral content of 436 healthy aged was measured and compared with that of 198 healthy, aged 21-50. Bone mineral content of postmenopausal females decreased continuously with age and bone mineral content of males began to decrease at age over 70. Bone width and menopausal age seemed to be important factors influencing bone mineral content, but previous physical activity seemed to have no effect on the bone mineral content of the aged.

Aged

Nucleosome stability safeguards cell identity, stress resilience and healthy aging.

Nucleosomes are the minimal repeating units of chromatin. Their dynamic assembly and disassembly underpins chromatin organization and genome regulation. However, it remains unclear how intrinsic nucleosome stability contributes to higher-level yet fundamental cellular and organismal properties-such as preservation of cell identity, lineage specification, stress resilience and ultimately healthy aging. To address this, we tested the impact of decreased intrinsic nucleosome stability across multiple cell, tissue and organismal models by introducing histone mutants that weaken histone-histone interactions. While nucleosome instability did not broadly alter global chromatin accessibility, DNA damage, cell proliferation or viability, it impaired lineage-specific gene expression programs, altered lineage specification and activated intrinsic inflammatory and stress pathways in a manner reminiscent of aging in mouse tissues and human cells. Consistently, nucleosome instability accelerated the onset of age-associated transcriptional alterations and functional decline in Caenorhabditis elegans and Drosophila melanogaster, and reduced cellular resilience to exogenous perturbations-including environmental, epigenetic and mitotic stress-in human cells and Saccharomyces cerevisiae. These cross-species findings identify nucleosome stability as an evolutionarily conserved epigenetic safeguard that preserves cell identity and stress resilience and supports organismal function and healthy aging.

Journal Article

Q-technique methodology in the study of healthy aged men: Part I.

The paper describes the application of the Q-technique to the study of healthy aged men. The research is an NIMH project, and the Q-technique was performed on the initial study done in 1957 (47 Ss across 550 variables). The paper focuses on clusters of interdisciplinary relationships which contained biological and cognitive influences. Twenty-eight out of the 64 clusters fell within this category. This first paper concentrates on methodological precedures and issues, and also presents 6 clusters of output derived from the first two Q-factors. The remaining 22 clusters will be described in subsequent papers.

Aged

Event-related potential changes in healthy aged females.

Neurophysiological changes in the central nervous system were demonstrated with EEG even-related potentials in healthy, aged women. Compared to young women, the aged women showed decreased amplitude of the late sustained potential (SP), increased P2 latency, disruption of the normal stimulus intensity-response amplitude function of P2 and increased amplitude of the P1 component. These age-related changes are interpreted as neurophysiological reflections of CNS deterioration found in non-senile elderly persons.

Adult

Characterizing midlife-onset alcohol dependence: Implications for etiology, prevention, and healthy aging.

We evaluated the developmental epidemiology of midlife-onset alcohol dependence (AD) in the Dunedin Study (N=1,037), a population-representative cohort followed across five decades. At ages 18, 21, 26, 32, 38, and 45, past-year AD prevalence was 11.0%, 18.4%, 13.6%, 8.1%, 9.6%, and 11.3%, respectively. As expected, relative to never-diagnosed individuals, those with early-onset AD (first diagnosis: age-18 or age-21, prevalence=22.9%) were distinguished by a range of early-life and adult correlates. Individuals with midlife-onset AD (first diagnosis: age-38 or age-45, prevalence=5.6%) were distinguished by fewer early-life correlates, but exhibited a family history of AD, and adolescent dysregulation and marijuana-use. They were characterized by an array of adult correlates, including internalizing disorders, mental-health treatment-contact, criminal-behavior, perceived-stress, coping-by-drinking, lower likelihood of marriage and parenthood, and reduced preparedness for old age. They also experienced more adult alcohol-related impairment than the early-onset group. Results can guide efforts to reduce midlife alcohol-related problems and support healthy aging.

Journal Article

Exponential analysis of elastic recoil and aging in healthy males and females.

To examine the effects of aging on the elasticity of the lungs a single exponential function (V = A - B exp (-KP)), where V is lung volume, P is recoil pressure, and A, B, and K are constants) and a fourth-order polynomial were fitted to the static pressure-volume data from 124 healthy nonsmokers (83 males). K, the index of compliance, was independent of sex and increased with age. B/A and recoil pressures at various lung volumes were higher in males than females, but decreases with age were similar in both sexes. Static compliance (expressed as percent of total lung capacity/cmH2O), derived from the polynomial expression, was the same in males and females and increased with age. The results show that the lungs of males and females have the same intrinsic elasticity, and differences in recoil pressure depend on differences in lung size and in maximum distending forces. Loss of elasticity with age is consistent with an increase in the unstressed dimensions of alveoli and a decrease in their elastic fibers.

Adolescent

[Synthesis of natural allohemagglutinins of the ABO system in healthy children aged 3 months to 3 years].

The work was carried out to establish the titre and score of haemagglutination of natural anti-A and anti-B antibodies in healthy children during the first three years of life. The material studied included 900 healthy children aged between 3 months and 3 years and 100 adults serving as controls. The method of test tube haemagglutination was used for determining the titre and score of alloagglutinins in relation to standard erythrocytes always obtained from the same donors. In addition, in 72 children and 10 adults the levels of IgG, IgA and IgM were determined quantitatively. A statistical analysis of the results showed that the levels of anti-A and anti-B alloagglutinins were relatively high at the age of 3 months / about 25% of the adult levels / and increased very rapidly in the first years of life reaching about 90% of the adult level at the end of the 3rd year of life. Besides that, it was demonstrated that it is useful in clinical practice to use the titre and score of natural alloagglutinins as indicators of humoral immunity, especially in children in the first years of life. Acceleration was demonstrated in the intensity of haemagglutination of natural antibodies in the last 40 years since their titre in the contemporary infantile population / up to the age of 1 year / is about 50% higher than that found in 1929. These findings suggest that increased immune reactivity of children observed presently may be due to prophylactic vaccinations.

ABO Blood-Group System

The iron status in healthy individuals aging from 18-25 years.

The haemoglobin, haematocrit, erythrocyte count, transferrin and serum iron values of a group of 65 healthy young people aging from 18-25 years were determined. Ferritin in serum was quantitated by radioimmunoassay to determine the usefulness of this assay in reflecting iron stores of healthy people.

Adolescent

Monovalent inactivated A/New Jersey/8/76 (Hsw1N1) vaccine in healthy children aged three to five years.

Single doses (50, 100, or 200 chick cell-agglutinating [CCA] units) of split-product or whole-virus (50 or 100 CCA units), monovalent inactivated A/New Jersey/8/76 (Hsw1n1) virus vaccine or placebo were given to healthy children aged three to five years in Maryland. Split-product vaccine was nonreactogenic but also virtually nonimmunogenic. Lower doses of whole-virus vaccine (50 CCA units of Merck, Sharp and Dohme [West Point, Pa.] and 50 or 100 CCA units of Merrell-National Laboratories [Cincinnati, Ohio] vaccine) were mildly reactogenic (approximately 25% of the children had low-grade fevers of 100 F-101 F). These dosage levels of whole-virus vaccine stimulated titers of greater than or equal to 1:20 in 68% and titers of greater than or equal to 1:40 in 37% of the children. Two inoculations of whole-virus vaccine (primary immunization followed by a booster one month later) were tolerated and induced titers of greater than or equal to 1:80 in 100% of the children.

Child, Preschool

Oscillations in reverse triiodothyronine levels in serum of healthy infants aged 0 to 130 hours.

rT3 was measured by RIA in sera from 273 normal healthy infants between 0--130 h of age. The curve for the mean rT3 level plotted against age was polyexponential in shape and showed superimposed oscillations with a period of about 16 h, similar to the curves for T4, T3, and TSH previously found for the same group of subjects (J Clin Endocrinol Metab 47: 61, 1978). The ratio of concentrations of rT3 to T4 remained approximately constant, with a mean value of 0.016 over the age range of 3--130 h. These observations suggest that the variations in rT3 levels in newborn serum during the first few days of life are largely accountable by variations in T4 substrate concentrations.

Humans

A genome-wide association study identified 10 novel genomic loci associated with intrinsic capacity.

BACKGROUND: Intrinsic capacity (IC) is a multidimensional concept within the World Health Organization framework for healthy aging. It refers to the composite of an individual's physical and mental capacities that enable them to maintain well-being, functional ability, and engagement in valued activities throughout life. While substantial evidence supports the biological basis of IC and its subdomains, the extent to which genetic factors influence IC remains largely unexplored, with no studies currently available. METHODS: Using datasets from the UK Biobank (UKB; N = 44 631) and the Canadian Longitudinal Study on Aging (CLSA; N = 13 085), we implemented the restricted maximum likelihood method to estimate SNP-based heritability (h2snp), followed by a Genome-Wide Association Study (GWAS) to identify genetic variants associated with IC, and post-GWAS analyses to pinpoint biological implications. RESULTS: The h2snp for IC was estimated at 25.2% in UKB and 19.5% in CLSA. Our GWAS identified 38 independent SNPs for IC across 10 genomic loci and 4289 candidate SNPs, mapped to 197 genes. Post-GWAS analysis revealed the role of these genes in cellular processes such as cell proliferation, immune function, metabolism, and neurodegeneration, with high expression in muscle, heart, brain, adipose, and nerve tissues. Of the 52 traits tested, 23 showed significant genetic correlations with IC, and a higher genetic loading for IC was associated with higher IC scores. CONCLUSIONS: Overall, this study provides comprehensive evidence on the genetic architecture of IC, identifying novel genetic variants and biological pathways, advancing our current knowledge and laying the foundation for ongoing and future research on healthy aging.

Adult

Clinical reactions and serologic responses in healthy children aged six to 35 months after two-dose regimens of inactivated A/New Jersey/76 influenza virus vaccines.

In collaborative clinical trials, two-dose regimens of four monovalent A/New Jersey (NJ)/76 influenza virus vaccines were evaluated in 89 children aged six to 35 months. Clinical reactions to vaccination consisted primarily of low-grade fever. Rectal temperatures of between 100 F and 102 F occurred less frequently after inoculation with split-product vaccines (seven [23%] of 31 children) than whole-virus vaccines (19 [33%] of 58). After administration of single doses of vaccines, titers of hemagglutination-inhibiting (HAI) antibody reached greater than or equal to 1:20 in three (13%) of the 23 recipients of split-product vaccines and in 23 (51%) of the 45 recipients of whole-virus vaccines. After administration of two doses, 89%-94% of recipients of Parke, Davis and Company (PD, Detroit, Mich.), Merrell-National Laboratories (Cincinnati, Ohio), and Merck Sharp and Dohme (West Point, Pa.) vaccines, but only 50% of the recipients of Wyeth Laboratories (Philadelphia, Pa.) vaccine, had titers of HAI antibody of greater than or equal to 1:20. Single doses of more reactogenic whole-virus vaccines may be justifiable for rapid immunization of young children during epidemics of influenza. Given in a two-dose regimen, however, PD split-product vaccine was immunogenic and was the most well-tolerated vaccine tested in this age group.

Antibodies, Viral