ACTN3, Morbidity, and Healthy Aging.
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ABSTRACT:
SUBMITTER: Pickering C
PROVIDER: S-EPMC5787547 | biostudies-literature | 2018
REPOSITORIES: biostudies-literature
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Project description:Homozygosity for a premature stop codon (X) in the ACTN3 "sprinter" gene is common in humans despite the fact that it reduces muscle size, strength and power. Because of the close relationship between skeletal muscle function and cardiometabolic health we examined the influence of ACTN3 R577X polymorphism over cardiovascular and metabolic characteristics of young adults (n = 98 males, n = 102 females; 23 ± 4.2 years) from our Assessing Inherent Markers for Metabolic syndrome in the Young (AIMMY) study. Both males and females with the RR vs XX genotype achieved higher mean VO2 peak scores (47.8 ± 1.5 vs 43.2 ±1.8 ml/O2/min, p = 0.002) and exhibited higher resting systolic (115 ± 2 vs 105 ± mmHg, p = 0.027) and diastolic (69 ± 3 vs 59 ± 3 mmHg, p = 0.005) blood pressure suggesting a role for ACTN3 in the maintenance of vascular tone. We subsequently identified the expression of alpha-actinin 3 protein in pulmonary artery smooth muscle, which may explain the genotype-specific differences in cardiovascular adaptation to acute exercise. In addition, we utilized targeted serum metabolomics to distinguish between RR and XX genotypes, suggesting an additional role for the ACTN3 R577X polymorphism in human metabolism. Taken together, these results identify significant cardiometabolic effects associated with possessing one or more functional copies of the ACTN3 gene.
| S-EPMC4480966 | biostudies-literature
Project description:ObjectivesTo study the association between multi-morbidity percentiles, which is a measure of clinical aging, and interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α.MethodsParticipants 50 to 95 years of age from the Mayo Clinic Study of Aging were assigned age- and sex-specific multi-morbidity percentiles using look-up tables that were reported previously (n = 1646). Percentiles were divided into quintiles for analysis. Plasma IL-6, IL-10, and TNF-α levels were measured in 1595 participants. Median inflammatory marker levels were compared across multi-morbidity quintiles using nonparametric tests.ResultsPeople with higher multi-morbidity percentiles had significantly higher IL-6 and TNF-α levels compared with those with lower multi-morbidity percentiles. Tests for trend across five multi-morbidity quintiles were significant among women for IL-6 and among participants 70 years of age or older for IL-6 and TNF-α. IL-10 was not associated with multi-morbidity percentiles.ConclusionsMulti-morbidity percentiles may be a useful clinical index of biological age for future studies, particularly in women and people 70 years of age and older.
| S-EPMC9274410 | biostudies-literature
Project description:ACTN3 encodes the protein α-actinin-3, which affects the muscle phenotype. In the present study, we examined the association of ACTN3 R577X polymorphism with body somatotype and cardiorespiratory fitness in young, healthy adults. The study group included 304 young adults, in whom cardiorespiratory fitness was evaluated and the maximum oxygen uptake was determined directly. The somatotype components were calculated according to the Heath-Carter method. Genotyping for the ACTN3 gene was performed using a polymerase chain reaction followed by high-resolution melting analysis. In the female group, a lower maximal heart rate (HRmax) was more strongly associated with the RR genotype (p = 0.0216) than with the RX and XX genotypes. In the male group, the ACTN3 RX genotype, as compared with other genotypes, tended to be associated with a lower percentage of adipose tissue (p = 0.0683), as also reflected by the body mass index (p = 0.0816). ACTN3 gene polymorphism may affect cardiorespiratory fitness. Our analysis of ACTN3 gene polymorphism does not clearly illustrate the relationships among genotype, body composition, and somatotype in young, healthy adults.
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Project description:The study of cognitive change across a life span, both in pathological and healthy samples, has been heavily influenced by developments in cognitive psychology as a theoretical paradigm, neuropsychology and other bio-medical fields; this alongside the increase in new longitudinal and cohort designs, complemented in the last decades by the evaluation of experimental interventions. Here, a review of aging databases was conducted, looking for the most relevant studies carried out on cognitive functioning in healthy older adults. The aim was to review not only longitudinal, cross-sectional or cohort studies, but also by intervention program evaluations. The most important studies, searching for long-term patterns of stability and change of cognitive measures across a life span and in old age, have shown a great range of inter-individual variability in cognitive functioning changes attributed to age. Furthermore, intellectual functioning in healthy individuals seems to decline rather late in life, if ever, as shown in longitudinal studies where age-related decline of cognitive functioning occurs later in life than indicated by cross-sectional studies. The longitudinal evidence and experimental trials have shown the benefits of aerobic physical exercise and an intellectually engaged lifestyle, suggesting that bio-psycho-socioenvironmental factors concurrently with age predict or determine both positive or negative change or stability in cognition in later life.
| S-EPMC7908458 | biostudies-literature
Project description:The process of aging results in a host of changes at the cellular and molecular levels, which include senescence, telomere shortening, and changes in gene expression. Epigenetic patterns also change over the lifespan, suggesting that epigenetic changes may constitute an important component of the aging process. The epigenetic mark that has been most highly studied is DNA methylation, the presence of methyl groups at CpG dinucleotides. These dinucleotides are often located near gene promoters and associate with gene expression levels. Early studies indicated that global levels of DNA methylation increase over the first few years of life and then decrease beginning in late adulthood. Recently, with the advent of microarray and next-generation sequencing technologies, increases in variability of DNA methylation with age have been observed, and a number of site-specific patterns have been identified. It has also been shown that certain CpG sites are highly associated with age, to the extent that prediction models using a small number of these sites can accurately predict the chronological age of the donor. Together, these observations point to the existence of two phenomena that both contribute to age-related DNA methylation changes: epigenetic drift and the epigenetic clock. In this review, we focus on healthy human aging throughout the lifetime and discuss the dynamics of DNA methylation as well as how interactions between the genome, environment, and the epigenome influence aging rates. We also discuss the impact of determining 'epigenetic age' for human health and outline some important caveats to existing and future studies.
| S-EPMC4693469 | biostudies-other
Project description:With increasing life expectancies worldwide, it is an important public health issue to identify factors that influence the quality of aging. We aimed to investigate the individual and combined roles of lifestyle factors at midlife for healthy aging (HA). We analyzed data from 2203 participants of the French ”Supplémentation en Vitamines et Minéraux Antioxydants” (SU.VI.MAX) cohort aged 45?60 years at baseline (1994?1995), and assessed the combined impact of lifestyle factors (weight, smoking status, physical activity, alcohol consumption, and diet) on HA (absence of chronic diseases and function-limiting pain, good physical and cognitive functioning, functional independence, no depressive symptoms, and good social and self-perceived health) with a five-component healthy lifestyle index (HLI). Relative risks (RR) and 95% confidence intervals (CIs) were estimated using a robust-error-variance Poisson regression. Approximately 39% of our sample aged healthily. After adjustment for potential confounders, a one-point increase in HLI was related to an 11% higher probability of HA (95% CI = 6%, 16%; p < 0.001). The proportions of HA attributable to specific factors based on the “population attributable risk” concept were 7.6%, 6.0%, 7.8%, and 16.5% for body mass index (BMI), physical activity, diet quality, and smoking status, respectively. This study highlights the importance of healthy lifestyle habits at midlife for the promotion of good overall health during aging.
| S-EPMC6073192 | biostudies-literature
Project description:Hippocampal sclerosis of aging (HS-Aging) is a causative factor in a large proportion of elderly dementia cases. The current definition of HS-Aging rests on pathologic criteria: neuronal loss and gliosis in the hippocampal formation that is out of proportion to AD-type pathology. HS-Aging is also strongly associated with TDP-43 pathology. HS-Aging pathology appears to be most prevalent in the oldest-old: autopsy series indicate that 5-30 % of nonagenarians have HS-Aging pathology. Among prior studies, differences in study design have contributed to the study-to-study variability in reported disease prevalence. The presence of HS-Aging pathology correlates with significant cognitive impairment which is often misdiagnosed as AD clinically. The antemortem diagnosis is further confounded by other diseases linked to hippocampal atrophy including frontotemporal lobar degeneration and cerebrovascular pathologies. Recent advances characterizing the neurocognitive profile of HS-Aging patients have begun to provide clues that may help identify living individuals with HS-Aging pathology. Structural brain imaging studies of research subjects followed to autopsy reveal hippocampal atrophy that is substantially greater in people with eventual HS-Aging pathology, compared to those with AD pathology alone. Data are presented from individuals who were followed with neurocognitive and neuroradiologic measurements, followed by neuropathologic evaluation at the University of Kentucky. Finally, we discuss factors that are hypothesized to cause or modify the disease. We conclude that the published literature on HS-Aging provides strong evidence of an important and under-appreciated brain disease of aging. Unfortunately, there is no therapy or preventive strategy currently available.
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Project description:INTRODUCTION:Optimism-the expectation that good things will happen-has emerged as a promising health asset, as it appears to be related to healthier behaviors and reduced disease risk. Growing research finds that higher optimism is associated with lower mortality, yet it is critical to understand whether this prolonged longevity is accompanied by good health. This study tested whether higher optimism was associated with increased likelihood of healthy aging. METHODS:Prospective data analyzed in 2018 from the Nurses' Health Study included 33,326 women with no major chronic diseases at baseline. Poisson regression models evaluated if optimism was associated with healthy aging 8 years later, considering potential confounders (sociodemographic variables, depression) and intermediate variables (health behaviors). Optimism was assessed in 2004 by validated self-report using mailed questionnaires and healthy aging was assessed in 2012, defined as (1) remaining free of major chronic diseases; (2) having no subjective memory impairment; (3) having intact physical function; and (4) surviving through follow-up. RESULTS:Overall, 20.5% of women (n=6,823) fulfilled the definition of healthy aging in 2012. After adjusting for sociodemographic factors and depression, the most (top quartile) versus least (bottom quartile) optimistic women had a 23% greater likelihood of healthy aging (95% CI=1.16, 1.30). Associations were similar in white and black participants, although the sample of black women was small (n=354). CONCLUSIONS:Higher optimism was associated with increased likelihood of healthy aging, suggesting that optimism, a potentially modifiable health asset, merits further research for its potential to improve health in aging.
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Project description:Autophagy is a fundamental cellular process that eliminates molecules and subcellular elements, including nucleic acids, proteins, lipids and organelles, via lysosome-mediated degradation to promote homeostasis, differentiation, development and survival. While autophagy is intimately linked to health, the intricate relationship among autophagy, aging and disease remains unclear. This Review examines several emerging features of autophagy and postulates how they may be linked to aging as well as to the development and progression of disease. In addition, we discuss current preclinical evidence arguing for the use of autophagy modulators as suppressors of age-related pathologies such as neurodegenerative diseases. Finally, we highlight key questions and propose novel research avenues that will likely reveal new links between autophagy and the hallmarks of aging. Understanding the precise interplay between autophagy and the risk of age-related pathologies across organisms will eventually facilitate the development of clinical applications that promote long-term health.
| S-EPMC8659158 | biostudies-literature
Project description:Objectives: Cognitive aging has been extensively investigated using both univariate and multivariate analyses. Sophisticated multivariate approaches such as graph theory could potentially capture unknown complex associations between multiple cognitive variables. The aim of this study was to assess whether cognition is organized into a structure that could be called the "cognitive connectome," and whether such connectome differs between age groups. Methods: A total of 334 cognitively unimpaired individuals were stratified into early-middle-age (37-50 years, n = 110), late-middle-age (51-64 years, n = 106), and elderly (65-78 years, n = 118) groups. We built cognitive networks from 47 cognitive variables for each age group using graph theory and compared the groups using different global and nodal graph measures. Results: We identified a cognitive connectome characterized by five modules: verbal memory, visual memory-visuospatial abilities, procedural memory, executive-premotor functions, and processing speed. The elderly group showed reduced transitivity and average strength as well as increased global efficiency compared with the early-middle-age group. The late-middle-age group showed reduced global and local efficiency and modularity compared with the early-middle-age group. Nodal analyses showed the important role of executive functions and processing speed in explaining the differences between age groups. Conclusions: We identified a cognitive connectome that is rather stable during aging in cognitively healthy individuals, with the observed differences highlighting the important role of executive functions and processing speed. We translated the connectome concept from the neuroimaging field to cognitive data, demonstrating its potential to advance our understanding of the complexity of cognitive aging.
| S-EPMC8416612 | biostudies-literature