Quality of life after traumatic brain injury: a cross-sectional analysis uncovers age- and sex-related differences over the adult life span.
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ABSTRACT:
SUBMITTER: Rauen K
PROVIDER: S-EPMC8050174 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundGrowing evidence suggests that epigenetic mechanisms of gene regulation may play a role in susceptibilities to specific toxicities and adverse drug reactions. MiRNAs in particular have been shown to be important regulators in cancer and other diseases and show promise as predictive biomarkers for diagnosis and prognosis. In this study, we characterized the global kidney miRNA expression profile in untreated male and female F344 rats throughout the life span. These findings were correlated with sex-specific susceptibilities to adverse renal events, such as male-biased renal fibrosis and inflammation in old age.MethodsKidney miRNA expression was examined in F344 rats at 2, 5, 6, 8, 15, 21, 78, and 104 weeks of age in both sexes using Agilent miRNA microarrays. Differential expression was determined using filtering criteria of ≥1.5 fold change and ANOVA or pairwise t-test (FDR <5%) to determine significant age and sex effects, respectively. Pathway analysis software was used to investigate the possible roles of these target genes in age- and sex-specific differences.ResultsThree hundred eleven miRNAs were found to be expressed in at least one age and sex. Filtering criteria revealed 174 differentially expressed miRNAs in the kidney; 173 and 34 miRNAs exhibiting age and sex effects, respectively. Principal component analysis revealed age effects predominated over sex effects, with 2-week miRNA expression being much different from other ages. No significant sexually dimorphic miRNA expression was observed from 5 to 8 weeks, while the most differential expression (13 miRNAs) was observed at 21 weeks. Potential target genes of these differentially expressed miRNAs were identified.ConclusionsThe expression of 56% of detected renal miRNAs was found to vary significantly with age and/or sex during the life span of F344 rats. Pathway analysis suggested that 2-week-expressed miRNAs may be related to organ and cellular development and proliferation pathways. Male-biased miRNA expression at older ages correlated with male-biased renal fibrosis and mononuclear cell infiltration. These miRNAs showed high representation in renal inflammation and nephritis pathways, and included miR-214, miR-130b, miR-150, miR-223, miR-142-5p, miR-185, and miR-296*. Analysis of kidney miRNA expression throughout the rat life span will improve the use of current and future renal biomarkers and inform our assessments of kidney injury and disease.
| S-EPMC4316605 | biostudies-literature
Project description:BackgroundThe sex gap in life expectancy has been narrowing in Finland over the past 4-5 decades; however, on average, women still live longer than men. Epigenetic clocks are markers for biological aging which predict life span. In this study, we examined the mediating role of lifestyle factors on the association between sex and biological aging in younger and older adults.MethodsOur sample consists of younger and older twins (21‒42 years, n = 1 477; 50‒76 years, n = 763) including 151 complete younger opposite-sex twin pairs (21‒30 years). Blood-based DNA methylation was used to compute epigenetic age acceleration by 4 epigenetic clocks as a measure of biological aging. Path modeling was used to study whether the association between sex and biological aging is mediated through lifestyle-related factors, that is, education, body mass index, smoking, alcohol use, and physical activity.ResultsIn comparison to women, men were biologically older and, in general, they had unhealthier life habits. The effect of sex on biological aging was partly mediated by body mass index and, in older twins, by smoking. Sex was directly associated with biological aging and the association was stronger in older twins.ConclusionsPreviously reported sex differences in life span are also evident in biological aging. Declining smoking prevalence among men is a plausible explanation for the narrowing of the difference in life expectancy between the sexes. Data generated by the epigenetic clocks may help in estimating the effects of lifestyle and environmental factors on aging and in predicting aging in future generations.
| S-EPMC9434475 | biostudies-literature
Project description:BackgroundPhysiological factors such as age and sex have been shown to be risk factors for adverse effects in the liver, including liver diseases and drug-induced liver injury. Previously, we have reported age- and sex-related significant differences in hepatic basal gene expression in rats during the life span that may be related to susceptibility to such adverse effects. However, the underlying mechanisms of the gene expression changes were not fully understood. In recent years, increasing evidence for epigenetic mechanisms of gene regulation has fueled interest in the role of microRNAs (miRNAs) in toxicogenomics and biomarker discovery. We therefore proposed that significant age and sex differences exist in baseline liver miRNA expression, and that comprehensive profiling of miRNAs will provide insights into the epigenetic regulation of gene expression in rat liver.MethodsTo address this, liver tissues from male and female F344 rats were examined at 2, 5, 6, 8, 15, 21, 52, 78, and 104 weeks of age for the expression of 677 unique miRNAs. Following data processing, predictive pathway analysis was performed on selected miRNAs that exhibited prominent age and/or sex differences in expression.ResultsOf the 314 miRNAs found to be expressed, 214 were differentially expressed; 65 and 212 miRNAs showed significant (false discovery rate (FDR) <5% and ≥1.5-fold change) sex- and age-related differences in expression, respectively. Thirty-eight miRNAs showed 2-week-specific expression, of which 31 miRNAs were found to be encoded within the Dlk1-Dio3 cluster located on chromosome 6. This cluster has been associated with tissue proliferation and differentiation, and liver energy homeostasis in postnatal development. Predictive pathway analysis linked sex-biased miRNA expression with sexually dimorphic molecular functions and toxicological functions that may reflect sex differences in hepatic physiology and disease. The expression of miRNAs (miR-18a, miR-99a, and miR-203, miR-451) was also found to associate with specific sexually dimorphic hepatic histopathology. The expression of miRNAs involved in regulating cell death, cell proliferation, and cell cycle was found to change as the rats matured from adult to old age.ConclusionsOverall, significant age- and sex-related differences in liver miRNA expression were identified and linked to histopathological findings and predicted functional pathways that may underlie susceptibilities to liver toxicity and disease.
| S-EPMC5291947 | biostudies-literature
Project description:Typical cognitive aging may be defined as age-associated changes in cognitive performance in individuals who remain free of dementia. Ideally, the full adult age spectrum should be included to assess brain imaging findings associated with typical aging.To compare age, sex, and APOE ?4 effects on memory, brain structure (adjusted hippocampal volume [HVa]), and amyloid positron emission tomography (PET) in cognitively normal individuals aged 30 to 95 years old.Cross-sectional observational study (March 2006 to October 2014) at an academic medical center. We studied 1246 cognitively normal individuals, including 1209 participants aged 50 to 95 years old enrolled in a population-based study of cognitive aging and 37 self-selected volunteers aged 30 to 49 years old.Memory, HVa, and amyloid PET.Overall, memory worsened from age 30 years through the 90s. The HVa worsened gradually from age 30 years to the mid-60s and more steeply beyond that age. The median amyloid PET was low until age 70 years and increased thereafter. Memory was worse in men than in women overall (P <?.001) and more specifically beyond age 40 years. The HVa was lower in men than in women overall (P <?.001) and more specifically beyond age 60 years. There was no sex difference in amyloid PET at any age. Within each sex, memory performance and HVa were not different by APOE ?4 status at any age. From age 70 years onward, APOE ?4 carriers had significantly greater median amyloid PET than noncarriers. However, the ages at which 10% of the population were amyloid PET positive were 57 years for APOE ?4 carriers and 64 years for noncarriers.Male sex is associated with worse memory and HVa among cognitively normal individuals, while APOE ?4 is not. In contrast, APOE ?4 is associated with greater amyloid PET (from age 70 years onward), while sex is not. Worsening memory and HVa occur at earlier ages than abnormal amyloid PET. Therefore, neuropathological processes other than ?-amyloidosis must underlie declines in brain structure and memory function in middle age. Our findings are consistent with a model of late-onset Alzheimer disease in which ?-amyloidosis arises in later life on a background of preexisting structural and cognitive decline that is associated with aging and not with ?-amyloid deposits.
| S-EPMC4428984 | biostudies-literature
Project description:Executive function (EF) refers to a set of cognitive functions that support goal-directed behaviors. Recent findings have suggested that the frontoparietal network (FPN) subserves neural processes that are related to EF. However, the FPN structural and functional network properties that mediate age-related differences in EF components remain unclear. To this end, we used three experimental tasks to test the component processes of EF based on Miyake and Friedman's model: one common EF component process (incorporating inhibition, shifting, and updating) and two specific EF component processes (shifting and updating). We recruited 126 healthy participants (65 females; 20 to 78 years old) who underwent both structural and functional MRI scanning. We tested a mediation path model of three structural and functional properties of the FPN (i.e., gray matter volume, white matter fractional anisotropy, and intra/internetwork functional connectivity) as mediators of age-related differences in the three EF components. The results indicated that age-related common EF component differences are mediated by regional gray matter volume changes in both hemispheres of the frontal lobe, which suggests that structural changes in the frontal lobe may have an indirect influence on age-related general elements of EF. These findings suggest that the FPN mediates age-related differences in specific components of EF.
| S-EPMC7271169 | biostudies-literature
Project description:Little is known regarding how the synthesis and degradation of individual proteins change during the life of an organism. Such knowledge is vital to understanding the aging process. To fill this knowledge gap, we monitored newly synthesized proteins on a proteome scale in Caenorhabditis elegans over time during adulthood using a stable-isotope labeling by amino acids in cell culture (SILAC)-based label-chase approach. For most proteins, the rate of appearance of newly synthesized protein was high during the first 5 days of adulthood, slowed down between the fifth and the 11th days, and then increased again after the 11th day. However, the magnitude of appearance rate differed significantly from protein to protein. For example, the appearance of newly synthesized protein was fast for proteins involved in embryonic development, transcription regulation, and lipid binding/transport, with >70% of these proteins newly synthesized by day 5 of adulthood, whereas it was slow for proteins involved in cellular assembly and motility, such as actin and myosin, with <70% of these proteins newly synthesized even on day 16. The late-life increase of newly synthesized protein was especially high for ribosomal proteins and ATP synthases. We also investigated the effect of RNAi-mediated knockdown of the rpl-9 (ribosomal protein), atp-3 (ATP synthase), and ril-1 (RNAi-induced longevity-1) genes and found that inhibiting the expression of atp-3 and ril-1 beginning in late adulthood is still effective to extend the life span of C. elegans.
| S-EPMC4440835 | biostudies-literature
Project description:Older adults are disproportionately targeted by fraud schemes that advertise unlikely but large returns (positively skewed risks). We examined adult age differences in choice and neural activity as individuals considered risky gambles. Gambles were symmetric (50% chance of modest win or loss), positively skewed (25% chance of large gain), or negatively skewed (25% chance of large loss). The willingness to accept positively skewed relative to symmetric gambles increased with age, and this effect replicated in an independent behavioral study. Whole-brain functional magnetic resonance imaging analyses comparing positively (vs. negatively) skewed trials revealed that relative to younger adults, older adults showed increased anticipatory activity for negatively skewed gambles but reduced activity for positively skewed gambles in the anterior cingulate and lateral prefrontal regions. Individuals who were more biased toward positively skewed gambles showed increased activity in a network of regions including the nucleus accumbens. These results reveal age biases toward positively skewed gambles and age differences in corticostriatal regions during skewed risk-taking, and have implications for identifying financial decision biases across adulthood.
| S-EPMC5709503 | biostudies-literature
Project description:BackgroundRecognition of loneliness as a health concern among adults stresses the need to understand the factors associated with loneliness. Research into factors of influence in the various phases of the adult life span (19-65 years) is scarce. Therefore, the associations between demographic, social and health-related factors and loneliness among young (19-34 years), early middle-aged (35-49 years) and late middle-aged adults (50-65 years) were explored.MethodsA secondary analysis with a large cross-sectional dataset was performed. Data was collected from September to December 2016 in the Netherlands, by a self-report survey. Loneliness was measured using the De Jong-Gierveld Loneliness Scale. In total, 26,342 adults (19-65 years) participated (response rate: 34%). Multiple logistic regression analyses were performed to examine associations between demographic, social and health-related factors as independent variables, and loneliness as dependent variable among the three age groups.ResultsPrevalence of loneliness among young, early and late middle-aged adults was 39.7, 43.3 and 48.2%, respectively. Living alone, frequency of neighbour contact, perceived social exclusion, psychological distress, psychological and emotional wellbeing were consistently associated with loneliness across the groups. The association between ethnicity and loneliness was stronger among young and early middle-aged adults, compared to late middle-aged adults. Young adults showed the strongest association between contact frequency with friends and loneliness. The strength of association between financial imbalance and loneliness gradually decreased from young to late middle-aged adults. Educational level was associated with loneliness among young adults only, while an association between employment status and loneliness was found solely among early middle-aged adults. For late middle-aged adults only, perceived health was associated with loneliness. Frequency of family contact was associated with loneliness, only among early and late middle-aged adults.ConclusionThis study indicates that factors associated with loneliness across the adult life span may be understood from an age-normative life-stage perspective. Accordingly, there is no one-size-fits-all approach to reduce loneliness among adults, suggesting that a variety of interventions or an indirect approach may be necessary. Future research should focus on causal relations between factors and loneliness in different age groups, using a longitudinal research-design with, preferably, an even broader set of factors.
| S-EPMC7409622 | biostudies-literature
Project description:BackgroundA number of large-scale population studies have provided valuable information about physical performance in aged individuals; however, there is little information about trajectories of function and associations with age across the adult life span. We developed a mobility-focused physical performance screener designed to be appropriate for the adult life span.MethodsThe physical performance battery includes measures of mobility, strength, endurance, and balance. Physical activity (PA) was assessed with accelerometry. We examined age-related trends in physical performance and PA, and the relationship between physical performance and PA across the age range (30-90+), by decade, in 775 participants enrolled in the study 2012-2014.ResultsPhysical performance was worse with increasing age decade. Although men performed better than women across all ages, the decrement by age group was similar between genders. Worsening physical performance was observed as early as the fifth decade for chair stands and balance and in the sixth decade for gait speed and aerobic endurance. The number and strength of significant associations between physical performance and PA increased with greater age: the greatest number of significant associations was seen in the 60-79 age groups, with fewer reported in the 30-59 and 80-90+ age groups. More PA was associated with better physical function.ConclusionThese results emphasize the importance of a life span approach to studies of function and aging. This work points to the need for a physical performance screener that spans across adulthood as a clinical tool for identifying functional decline.
| S-EPMC6075535 | biostudies-literature
Project description:As the emerging treatments that target grey matter pathology in Alzheimer's Disease have limited effectiveness, there is a critical need to identify new neural targets for treatments. White matter's (WM) metabolic vulnerability makes it a promising candidate for new interventions. This study examined the age and sex differences in estimates of axonal content, as well the associations of with highly prevalent modifiable health risk factors such as metabolic syndrome and adiposity. We estimated intra-axonal volume fraction (ICVF) using the Neurite Orientation Dispersion and Density Imaging (NODDI) in a sample of 89 cognitively and neurologically healthy adults (20-79 years). We showed that ICVF correlated positively with age and estimates of myelin content. The ICVF was also lower in women than men, across all ages, which difference was accounted for by intracranial volume. Finally, we found no association of metabolic risk or adiposity scores with the current estimates of ICVF. In addition, the previously observed adiposity-myelin associations (Burzynska et al., 2023) were independent of ICVF. Although our findings confirm the vulnerability of axons to aging, they suggest that metabolic dysfunction may selectively affect myelin content, at least in cognitively and neurologically healthy adults with low metabolic risk, and when using the specific MRI techniques. Future studies need to revisit our findings using larger samples and different MRI approaches, and identify modifiable factors that accelerate axonal deterioration as well as mechanisms linking peripheral metabolism with the health of myelin.
| S-EPMC10827486 | biostudies-literature