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The Journals of Gerontology. Series A,... Jan 2024DNA methylation-derived epigenetic clocks offer the opportunity to examine aspects of age acceleration (ie, the difference between an individual's biological age and...
DNA methylation-derived epigenetic clocks offer the opportunity to examine aspects of age acceleration (ie, the difference between an individual's biological age and chronological age), which vary among individuals and may better account for age-related changes in cognitive function than chronological age. Leveraging existing ambulatory cognitive assessments in daily life from a genetically diverse sample of 142 adults in midlife, we examined associations between 5 measures of epigenetic age acceleration and performance on tasks of processing speed and working memory. Covarying for chronological age, we used multilevel models to examine associations of epigenetic age acceleration (Horvath 1, Horvath 2, Hannum, PhenoAge, and GrimAge clocks) with both average level and variability of cognitive performance. Positive age acceleration (ie, epigenetic age greater than chronological age) was associated with poorer mean processing speed (Horvath 1 and 2) and working memory (GrimAge). Higher chronological age was also associated with poorer mean processing speed and working memory performance. Further, positive age acceleration was generally associated with greater intraindividual variability in working memory and processing speed tasks, whereas being chronologically older was associated with less intraindividual variability. Although further work is needed, our results indicate age acceleration effects have comparable or greater size as those for chronological age differences, suggesting that epigenetic age acceleration may account for additional risk and interindividual variation in cognitive performance above chronological age.
Topics: Humans; Aging; Epigenesis, Genetic; DNA Methylation; Cognition; Acceleration
PubMed: 37899644
DOI: 10.1093/gerona/glad242 -
CNS Neuroscience & Therapeutics Jul 2023Age and sex are important individual factors modifying the clinical symptoms of patients with Parkinson's disease (PD). Our goal is to evaluate the effects of age and...
AIMS
Age and sex are important individual factors modifying the clinical symptoms of patients with Parkinson's disease (PD). Our goal is to evaluate the effects of age and sex on brain networks and clinical manifestations of PD patients.
METHODS
Parkinson's disease participants (n = 198) receiving functional magnetic resonance imaging from Parkinson's Progression Markers Initiative database were investigated. Participants were classified into lower quartile group (age rank: 0%~25%), interquartile group (age rank: 26%~75%), and upper quartile group (age rank: 76%~100%) according to their age quartiles to examine how age shapes brain network topology. The differences of brain network topological properties between male and female participants were also investigated.
RESULTS
Parkinson's disease patients in the upper quartile age group exhibited disrupted network topology of white matter networks and impaired integrity of white matter fibers compared to lower quartile age group. In contrast, sex preferentially shaped the small-world topology of gray matter covariance network. Differential network metrics mediated the effects of age and sex on cognitive function of PD patients.
CONCLUSION
Age and sex have diverse effects on brain structural networks and cognitive function of PD patients, highlighting their roles in the clinical management of PD.
Topics: Humans; Male; Female; Parkinson Disease; Brain; Gray Matter; Magnetic Resonance Imaging; White Matter
PubMed: 36890620
DOI: 10.1111/cns.14149 -
BioRxiv : the Preprint Server For... Oct 2023The differentiation of human pluripotent stem cells (hPSCs) provides access to most cell types and tissues. However, hPSC-derived lineages capture a fetal-stage of...
The differentiation of human pluripotent stem cells (hPSCs) provides access to most cell types and tissues. However, hPSC-derived lineages capture a fetal-stage of development and methods to accelerate progression to an aged identity are limited. Understanding the factors driving cellular age and rejuvenation is also essential for efforts aimed at extending human life and health span. A prerequisite for such studies is the development of methods to score cellular age and simple readouts to assess the relative impact of various age modifying strategies. Here we established a transcriptional score (RNAge) in young versus old primary fibroblasts, frontal cortex and substantia nigra tissue. We validated the score in independent RNA-seq datasets and demonstrated a strong cell and tissue specificity. In fibroblasts we observed a reset of RNAge during iPSC reprogramming while direct reprogramming of aged fibroblasts to induced neurons (iN) resulted in the maintenance of both a neuronal and a fibroblast aging signature. Increased RNAge in hPSC-derived neurons was confirmed for several age-inducing strategies such as SATB1 loss, progerin expression or chemical induction of senescence (SLO). Using RNAge as a probe set, we next performed an in-silico screen using the LINCS L1000 dataset. We identified and validated several novel age-inducing and rejuvenating compounds, and we observed that RNAage captures age-related changes associated with distinct cellular hallmarks of age. Our study presents a simple tool to score age manipulations and identifies compounds that greatly expand the toolset of age-modifying strategies in hPSC derived lineages.
PubMed: 37461485
DOI: 10.1101/2023.07.03.547539 -
Frontiers in Nutrition 2023An increasing number of studies have demonstrated that gastrointestinal inflammation may increase prostate cancer risk and raise the prostate-specific antigen (PSA)...
Association of ulcerative colitis and acute gastroenteritis with prostate specific antigen: results from National Health and Nutrition Examination Survey from (2009 to 2010) and Mendelian randomization analyses.
BACKGROUND
An increasing number of studies have demonstrated that gastrointestinal inflammation may increase prostate cancer risk and raise the prostate-specific antigen (PSA) level. However, the association between ulcerative colitis (UC) and acute gastroenteritis (AGE) with PSA remains unclear and complicated. Herein, we evaluated the relationship between UC and AGE with PSA concentration using the National Health and Nutrition Examination Survey (NHANES) database and Mendelian randomization (MR) analyses.
MATERIALS AND METHODS
A total of 1,234 participants fit into the study after conducting the screening based on the NHANES survey conducted from 2009 to 2010. UC and AGE were the independent variables, and PSA was the dependent variable. Weighted multiple linear regressions were utilized to estimate the association of UC and AGE with PSA concentration. To detect the causal relationship between UC and AGE with PSA, a two-sample Mendelian randomized analysis was conducted.
RESULTS
After controlling for all covariates, PSA (log2 transform) concentrations in the UC group were increased by 0.64 (0.07, 1.21). AGE was not independently associated with PSA levels after adjusting potential confounders. In patients with coronary artery disease, AGE promotes elevated PSA (log2 transform) concentrations ( = 1.20, 95% CI: 0.21-2.20, < 0.001). Moreover, an IVW MR analysis indicated that genetically predicted UC was associated with increased PSA, and that AGE was not associated with PSA.
CONCLUSION
This study indicated that a positive causal association exists between UC and the PSA level. However, there is no evidence to support the relationship between AGE and the PSA level.
PubMed: 38111604
DOI: 10.3389/fnut.2023.1265014 -
Archives of Medical Science : AMS 2023The aim of the study was to examine the burden of uterine fibroids at global, regional and national levels in terms of age and the Socio-demographic Index (SDI).
INTRODUCTION
The aim of the study was to examine the burden of uterine fibroids at global, regional and national levels in terms of age and the Socio-demographic Index (SDI).
MATERIAL AND METHODS
Data were extracted from the GBD 2019 dataset. Estimated annual percentage changes (EAPCs) were calculated to assess the incidence of uterine fibroids, and trends in disability-adjusted life years (DALYs) were examined. All measures examined were stratified by region, country, age and SDI to assess the effects of these variables on the incidence of uterine fibroids.
RESULTS
The global age-standardized incidence rate of uterine fibroids increased from 1990 to 2019, with an EAPC of 0.25 (95% confidence interval (CI): 0.24 to 0.27). In contrast, the global age-standardized DALY rate decreased from 1990 to 2019, with an EAPC of -0.27 (95% CI: -0.31 to -0.23). High and low-middle SDI regions experienced significantly higher age-standardized incidence rates. Moreover, in 2019, low and low-middle SDI regions had significantly higher age-standardized DALY rates due to uterine fibroids than other SDI regions. Regionally, Eastern Europe had the highest age-standardized incidence rate of uterine fibroids in 2019, and Tropical Latin America experienced the greatest increase in age-standardized incidence rates from 1990 to 2019. Nationally, Brazil (EAPC = 1.46; 95% CI: 1.35-1.57) and India (EAPC = 1.09; 95% CI: 0.94-1.25) experienced the most significant increases in age-standardized uterine fibroid incidence. Age-standardized DALY rates increased the most in Tropical Latin America, high-income North America and Oceania.
CONCLUSIONS
Globally, the age-standardized incidence of uterine fibroids has been increasing in recent years. In contrast, age-standardized DALY rates have exhibited a decreasing trend. Eastern Europe, Tropical Latin America, Brazil and India experience the greatest uterine fibroid burden. Globally, women aged 35-39 years and older have an increased risk of uterine fibroids, as reflected in the higher incidence rates among these age groups.
PubMed: 38058724
DOI: 10.5114/aoms/171786 -
Aging Nov 2023Children from old fathers carry an increased risk for autism spectrum (ASD) and other neurodevelopmental disorders, which may at least partially be mediated by paternal...
Children from old fathers carry an increased risk for autism spectrum (ASD) and other neurodevelopmental disorders, which may at least partially be mediated by paternal age effects on the sperm epigenome. The brain enriched guanylate kinase associated (BEGAIN) protein is involved in protein-protein interactions at and transmission across synapses. Since several epigenome-wide methylation screens reported a paternal age effect on sperm methylation, here we confirmed a significant negative correlation between promoter methylation and paternal age, using more sensitive bisulfite pyrosequencing and a larger number of sperm samples. Paternal age-associated hypomethylation was also observed in fetal cord blood (FCB) of male but not of female offspring. There was no comparable maternal age effect on FCB methylation. In addition, we found a significant negative correlation between methylation and chronological age (ranging from 1 to 70 years) in peripheral blood samples of male but not of female donors. hypomethylation was more pronounced in male children, adolescents and adults suffering from ASD compared to controls. Both genetic variation (CC genotype of SNP rs7141087) and epigenetic factors may contribute to promoter hypomethylation. The age- and sex-specific methylation trajectories in the male germ line and somatic tissues, in particular the brain, support a role of this gene in ASD development.
Topics: Adolescent; Aged; Female; Humans; Male; Autistic Disorder; DNA Methylation; Epigenesis, Genetic; Fathers; Semen; Infant; Child, Preschool; Child; Young Adult; Adult; Middle Aged
PubMed: 38019471
DOI: 10.18632/aging.205275 -
Skin Research and Technology : Official... Aug 2023Age-related changes in scalp parameters affect hair quality and scalp condition. However, detailed data on biophysical parameters of the scalp across age groups remain...
BACKGROUND
Age-related changes in scalp parameters affect hair quality and scalp condition. However, detailed data on biophysical parameters of the scalp across age groups remain scarce. We aimed to investigate the differences in scalp parameters between individuals in their 20s and 50s and analyze their sex-specific variations.
MATERIALS AND METHODS
Two hundred participants (160 women and 40 men) were equally divided into 20s and 50s age groups. Biophysical parameters of the scalp, including elasticity, pH, trans-epidermal water loss (TEWL), sebum production, desquamation, firmness, redness, and yellowness, were measured in the vertex, occipital, and temporal regions. Hair density and thickness were measured in the temporal region. The accumulation of advanced glycation end products (AGEs) in the skin was noninvasively measured in a subset of 60 women.
RESULTS
Skin firmness and redness increased with age in women, whereas yellowness increased with age in both sexes. Sebum production and pH levels were significantly lower in the 50s age group than in the 20s age group, particularly in women. TEWL was lower in men in their 50s than in those in their 20s, particularly in the occipital region. A significant reduction in hair density was observed in the 50s age group in both sexes. AGE accumulation in the skin increased with age and was correlated with scalp skin yellowness.
CONCLUSION
Age-related changes in scalp parameters have important implications for hair health and scalp condition. These findings emphasize the importance of considering age and sex when developing hair care strategies.
Topics: Male; Female; Humans; Scalp; Skin; Hair; Epidermis; Biophysics
PubMed: 37632187
DOI: 10.1111/srt.13433 -
Cureus Jul 2023The aging of an organism is hallmarked by systemic loss of functional tissue, resulting in increased fragility and eventual development of age-related neurodegenerative,... (Review)
Review
The aging of an organism is hallmarked by systemic loss of functional tissue, resulting in increased fragility and eventual development of age-related neurodegenerative, musculoskeletal, cardiovascular, and neoplastic diseases. Growing scientific evidence points to mitochondrial dysfunction as a key contributor in the aging process and subsequent development of age-related pathologies. Under normal physiologic conditions, the body removes dysfunctional mitochondria via an autophagic process known as mitophagy. Urolithin A (UA), a metabolite produced when gut microflora digests the polyphenol compounds ellagitannin and ellagic acid, is a known inducer of mitophagy via several identified mechanisms of action. The primary objective of this scoping review is to identify and summarize the clinical relevance of UA supplementation in the prevention of age-related pathology and diseases. A computer-assisted literature review was performed using PubMed and EMBASE for primary source research articles examining UA supplementation and aging-related pathologies. A total of 293 articles were initially identified from a database search, and 15 articles remained for inclusion in this review, based on predetermined criteria. Analysis of the 15 identified publications demonstrated that UA holds potential as a dietary intervention for slowing the progression of aging and preventing the development of age-related disease. This review also illustrates the potential role that mitochondrial health and inflammation play in the progression of age-related pathology. Identifying the clinical relevance of UA supplementation in the prevention of age-related pathology and diseases will help further the focus of research on treatments that may improve the longevity and quality of life in patients at risk for these comorbidities.
PubMed: 37637627
DOI: 10.7759/cureus.42550 -
Forensic Sciences Research Jun 2023Estimating an individual's age can be relevant in several areas primarily related to the clinical and forensic fields. In the latter, estimation of an individual's... (Review)
Review
Estimating an individual's age can be relevant in several areas primarily related to the clinical and forensic fields. In the latter, estimation of an individual's chronological age from biological material left by the perpetrator at a crime scene may provide helpful information for police investigation. Estimation of age is also beneficial in immigration cases, where age can affect the person's protection status under the law, or in disaster victim identification to narrow the list of potential missing persons. In the last decade, research has focused on establishing new approaches for age prediction in the forensic field. From the first forensic age estimations based on morphological inspections of macroscopic changes in bone and teeth, the focus has shifted to molecular methods for age estimation. These methods allow the use of samples from human biological material that does not contain morphological age features and can, in theory, be investigated in traces containing only small amounts of biological material. Molecular methods involving DNA analyses are the primary choice and estimation of DNA methylation levels at specific sites in the genome is the most promising tool. This review aims to provide an overview of the status of forensic age prediction using molecular methods, with particular focus in DNA methylation. The frequent challenges that impact forensic age prediction model development will be addressed, together with the importance of validation efforts within the forensic community.
PubMed: 37621446
DOI: 10.1093/fsr/owad021 -
Annals of Medicine Dec 2024The incidence of mortality is considerable after ST-elevation myocardial infarction (STEMI) hospitalization; risk assessment is needed to guide postdischarge management....
BACKGROUND
The incidence of mortality is considerable after ST-elevation myocardial infarction (STEMI) hospitalization; risk assessment is needed to guide postdischarge management. Age shock index (SI) and age modified shock index (MSI) were described as useful prognosis instruments; nevertheless, their predictive effect on short and long-term postdischarge mortality has not yet been sufficiently confirmed.
METHODS
This analysis included 3389 prospective patients enrolled from 2016 to 2018. Endpoints were postdischarge mortality within 30 days and from 30 days to 1 year. Hazard ratios (HRs) were evaluated by Cox proportional-hazards regression. Predictive performances were assessed by area under the curve (AUC), integrated discrimination improvement (IDI), net reclassification improvement (NRI) and decision curve analysis (DCA) and compared with TIMI risk score and GRACE score.
RESULTS
The AUCs were 0.753, 0.746 for age SI and 0.755, 0.755 for age MSI for short- and long-term postdischarge mortality. No significant AUC differences and NRI were observed compared with the classic scores; decreased IDI was observed especially for long-term postdischarge mortality. Multivariate analysis revealed significantly higher short- and long-term postdischarge mortality for patients with high age SI (HR: 5.44 (2.73-10.85), 5.34(3.18-8.96)), high age MSI (HR: 4.17(1.78-9.79), 5.75(3.20-10.31)) compared to counterparts with low indices. DCA observed comparable clinical usefulness for predicting short-term postdischarge mortality. Furthermore, age SI and age MSI were not significantly associated with postdischarge prognosis for patients who received fibrinolysis.
CONCLUSIONS
Age SI and age MSI were valuable instruments to identify high postdischarge mortality with comparable predictive ability compared with the classic scores, especially for events within 30 days after hospitalization.
Topics: Humans; Infant; Prognosis; ST Elevation Myocardial Infarction; Prospective Studies; Aftercare; Retrospective Studies; Patient Discharge; Risk Assessment
PubMed: 38325361
DOI: 10.1080/07853890.2024.2311854