A natural constant predicts survival to maximum age.
Ontology highlight
ABSTRACT:
SUBMITTER: Dureuil M
PROVIDER: S-EPMC8166855 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:DNA methylation is a reaction that results in the formation of 5-methylcytosine when a methyl group is added to the cytosine’s C5 position. As organisms age, DNA methylation patterns change in a reproducible fashion. This phenomenon has established DNA methylation as a valuable biomarker in aging studies. Epigenetic clocks based on weighted combinations of methylation sites have been developed to accurately predict the age of an individual from their methylome. However, many epigenetic clocks, particularly those that utilize penalized regression, model the changes in methylation linearly with age. Moreover, these models, which use methylation levels as features, are not robust to missing data and do not account for the count-based nature of bisulfite sequence data. Additionally, the models are generally not interpretable. To overcome these challenges, we present BayesAge, an extension of the previously developed scAge approach that was developed for the analysis of single cell DNA methylation datasets. BayesAge utilizes maximum likelihood estimation (MLE) to infer ages, models count data using binomial distributions, and uses LOWESS smoothing to capture the non-linear dynamics between methylation and age. Our approach is designed for use with bulk bisulfite sequencing datasets. BayesAge outperforms scAge in several respects. Specifically, BayesAge’s age residuals are not age associated, thus providing a less biased representation of epigenetic age variation across populations. Moreover, BayesAge enables the estimation of error bounds on age inference and, when run on downsampled data, its coefficient of determination between predicted and actual ages surpasses both scAge and penalized regression.
2024-03-20 | GSE261769 | GEO
Project description:IntroductionPediatric liver transplant recipients have demonstrated excellent long-term survival. The purpose of this analysis is to investigate factors associated with 20-year survival to identify areas for improvement in patient care.MethodsKaplan-Meier with log-rank test as well as univariate and multivariate logistic regression methods were used to retrospectively analyze 4,312 liver transplant recipients under the age of 18 between September 30, 1987 and March 9, 1998. Our primary endpoint was 20-year survival among one-year survival.ResultsLogistic regression analysis identified recipient age as a significant risk factor, with recipients below 5 years old having a higher 20-year survival rate (p < 0.001). A preoperative primary diagnosis of a metabolic dysfunction was found to be protective compared to other diagnoses (OR 1.64, CI 1.20-2.25). African-American ethnicity (OR 0.71, CI 0.58-0.87) was also found to be a risk factor for mortality. Technical variant allografts (neither living donor nor cadaveric) were not associated with increased or decreased rates of 20-year survival.ConclusionsOur analysis suggests that long-term survival is inversely correlated with recipient age following pediatric liver transplant. If validated with further studies, this conclusion may have profound implications on the timing of pediatric liver transplantation.
| S-EPMC9509270 | biostudies-literature
Project description:A long-standing mystery in genome evolution is why short tandem repeats vary so much in length and frequency. Here, we test the hypothesis that body temperature acts to influence the rate and nature of slippage-based mutations. Using the data from both 28 species where genome sequencing is advanced and 76 species from which marker loci have been published, we show that in mammals, maximum repeat number is inversely correlated with body temperature, with warmer-blooded species having shorter 'long' microsatellites. Our results support a model of microsatellite evolution in which maximum length is limited by a temperature-dependent stability threshold.
| S-EPMC2610156 | biostudies-literature
Project description:Studying the genome of centenarians may give insights into the molecular mechanisms underlying extreme human longevity and the escape of age-related diseases. Here, we set out to construct polygenic risk scores (PRSs) for longevity and to investigate the functions of longevity-associated variants. Using a cohort of centenarians with maintained cognitive health (N = 343), a population-matched cohort of older adults from 5 cohorts (N = 2905), and summary statistics data from genome-wide association studies on parental longevity, we constructed a PRS including 330 variants that significantly discriminated between centenarians and older adults. This PRS was also associated with longer survival in an independent sample of younger individuals (p = .02), leading up to a 4-year difference in survival based on common genetic factors only. We show that this PRS was, in part, able to compensate for the deleterious effect of the APOE-ε4 allele. Using an integrative framework, we annotated the 330 variants included in this PRS by the genes they associate with. We find that they are enriched with genes associated with cellular differentiation, developmental processes, and cellular response to stress. Together, our results indicate that an extended human life span is, in part, the result of a constellation of variants each exerting small advantageous effects on aging-related biological mechanisms that maintain overall health and decrease the risk of age-related diseases.
| S-EPMC8087277 | biostudies-literature
Project description:Introduction Maximum bite force (MBF) is the maximum force performed by the subject on the fragmentation of food, directly related with the mastication and determined by many factors. Objective Analyze the MBF of subjects according to age groups. Methods One hundred individuals from the city of São Paulo were equally divided according to age groups and gender. Each individual submitted to a myotherapy evaluation composed of anthropometric measurements of height and weight to obtain body mass index (BMI), using a tape and a digital scale (Magna, G-life, São Paulo), and a dental condition and maximum bite force evaluation, using a digital dynamometer model DDK/M (Kratos, São Paulo, Brazil), on Newton scale. The dental and bite force evaluations were monitored by a professional from the area. Analysis of variance was used with MBF as a dependent variable, age group and gender as random factors, and BMI as a control variable. Results Till the end of adolescence, it was possible to observe a decrease in MBF in both sexes, with the male force greater than the female force. In young adults, the female force became greater the males, then decreased in adulthood. There was no correlation between MBF and BMI. Conclusion There are MBF variations that characterizes the human development stages, according to age groups.
| S-EPMC4297017 | biostudies-other
Project description:A rigorous understanding of brain dynamics and function requires a conceptual bridge between multiple levels of organization, including neural spiking and network-level population activity. Mounting evidence suggests that neural networks of cerebral cortex operate at a critical regime, which is defined as a transition point between two phases of short lasting and chaotic activity. However, despite the fact that criticality brings about certain functional advantages for information processing, its supporting evidence is still far from conclusive, as it has been mostly based on power law scaling of size and durations of cascades of activity. Moreover, to what degree such hypothesis could explain some fundamental features of neural activity is still largely unknown. One of the most prevalent features of cortical activity in vivo is known to be spike irregularity of spike trains, which is measured in terms of the coefficient of variation (CV) larger than one. Here, using a minimal computational model of excitatory nodes, we show that irregular spiking (CV > 1) naturally emerges in a recurrent network operating at criticality. More importantly, we show that even at the presence of other sources of spike irregularity, being at criticality maximizes the mean coefficient of variation of neurons, thereby maximizing their spike irregularity. Furthermore, we also show that such a maximized irregularity results in maximum correlation between neuronal firing rates and their corresponding spike irregularity (measured in terms of CV). On the one hand, using a model in the universality class of directed percolation, we propose new hallmarks of criticality at single-unit level, which could be applicable to any network of excitable nodes. On the other hand, given the controversy of the neural criticality hypothesis, we discuss the limitation of this approach to neural systems and to what degree they support the criticality hypothesis in real neural networks. Finally, we discuss the limitations of applying our results to real networks and to what degree they support the criticality hypothesis.
| S-EPMC5560579 | biostudies-literature
Project description:Senescence, the increase in mortality and decline in fertility with age after maturity, was thought to be inevitable for all multicellular species capable of repeated breeding. Recent theoretical advances and compilations of data suggest that mortality and fertility trajectories can go up or down, or remain constant with age, but the data are scanty and problematic. Here, we present compelling evidence for constant age-specific death and reproduction rates in Hydra, a basal metazoan, in a set of experiments comprising more than 3.9 million days of observations of individual Hydra. Our data show that 2,256 Hydra from two closely related species in two laboratories in 12 cohorts, with cohort age ranging from 0 to more than 41 y, have extremely low, constant rates of mortality. Fertility rates for Hydra did not systematically decline with advancing age. This falsifies the universality of the theories of the evolution of aging that posit that all species deteriorate with age after maturity. The nonsenescent life history of Hydra implies levels of maintenance and repair that are sufficient to prevent the accumulation of damage for at least decades after maturity, far longer than the short life expectancy of Hydra in the wild. A high proportion of stem cells, constant and rapid cell turnover, few cell types, a simple body plan, and the fact that the germ line is not segregated from the soma are characteristics of Hydra that may make nonsenescence feasible. Nonsenescence may be optimal because lifetime reproduction may be enhanced more by extending adult life spans than by increasing daily fertility.
| S-EPMC4697432 | biostudies-other
Project description:Background. The pretreatment albumin to globulin ratio (AGR) has been reported to be a predictor of survival in several types of cancer. The aim of this study was to evaluate the prognostic impact of AGR in patients with natural killer/T-cell lymphoma (NKTCL). Methods. We retrospectively reviewed the available serum biochemistry results for 331 NKTCL patients before treatment. AGR was calculated as albumin/(total protein-albumin), and a cut-off value of 1.3 was used to define AGR as low or high. Survival analysis was used to assess the prognostic value of AGR. Results. A low AGR (<1.3) was associated with significantly more adverse clinical features, including old age, poor performance status, advanced stage, elevated lactate dehydrogenase, B symptoms, and high International Prognostic Index (IPI) and natural killer/T-cell lymphoma prognostic index (NKPI) scores. Patients with a low AGR had a significantly lower 5-year overall survival (44.5 vs. 65.2%, P < 0.001) and progression-free survival (33.1 vs. 57.4%, P < 0.001). In the multivariate analysis, a low AGR remained an independent predictor of poorer survival. Additionally, AGR distinguished patients with different outcomes in the IPI low-risk group and in the NKPI high-risk group. Discussion. Pretreatment AGR may serve as a simple and effective predictor of prognosis in patients with NKTCL.
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Project description:Greater muscular strength is generally associated with superior sports performance, for example, in jumping, sprinting, and throwing. This meta-analysis aims to compare the effects of variable-resistance training (VRT) and constant-resistance training (CRT) on the maximum strength of trained and untrained subjects. PubMed, Web of Science, and Google Scholar were comprehensively searched to identify relevant studies published up to January 2022. Fourteen studies that met the inclusion criteria were used for the systematic review and meta-analysis. Data regarding training status, training modality, and type of outcome measure were extracted for the analyses. The Cochrane Collaboration tool was used to assess the risk of bias. The pooled outcome showed improved maximum strength with VRT, which was significantly higher than that with CRT (ES = 0.80; 95% CI: 0.42-1.19) for all the subjects. In addition, trained subjects experienced greater maximum-strength improvements with VRT than with CRT (ES = 0.57; 95% CI: 0.22-0.93). Based on subgroup analyses, maximum-strength improvement with a VRT load of ≥80% of 1 repetition maximum (1RM) was significantly higher than that with CRT (ES = 0.76; 95% CI: 0.37-1.16) in trained subjects, while no significant differences were found between VRT and CRT for maximum-strength improvement when the load was <80% (ES = 0.00; 95% CI: -0.55-0.55). The untrained subjects also achieved greater maximum strength with VRT than with CRT (ES = 1.34; 95% CI: 0.28-2.40). Interestingly, the improved maximum strength of untrained subjects with a VRT load of <80% of 1RM was significantly higher than that with CRT (ES = 2.38; 95% CI: 1.39-3.36); however, no significant differences were noted between VRT and CRT when the load was ≥80% of 1RM (ES = -0.04; 95% CI: -0.89-0.81). Our findings show that subjects with resistance training experience could use a load of ≥80% of 1RM and subjects without resistance training experience could use a load of <80% of 1RM to obtain greater VRT benefits.
| S-EPMC9317775 | biostudies-literature
Project description:Age-associated disease and disability are placing a growing burden on society. However, ageing does not affect people uniformly. Hence, markers of the underlying biological ageing process are needed to help identify people at increased risk of age-associated physical and cognitive impairments and ultimately, death. Here, we present such a biomarker, 'brain-predicted age', derived using structural neuroimaging. Brain-predicted age was calculated using machine-learning analysis, trained on neuroimaging data from a large healthy reference sample (N=2001), then tested in the Lothian Birth Cohort 1936 (N=669), to determine relationships with age-associated functional measures and mortality. Having a brain-predicted age indicative of an older-appearing brain was associated with: weaker grip strength, poorer lung function, slower walking speed, lower fluid intelligence, higher allostatic load and increased mortality risk. Furthermore, while combining brain-predicted age with grey matter and cerebrospinal fluid volumes (themselves strong predictors) not did improve mortality risk prediction, the combination of brain-predicted age and DNA-methylation-predicted age did. This indicates that neuroimaging and epigenetics measures of ageing can provide complementary data regarding health outcomes. Our study introduces a clinically-relevant neuroimaging ageing biomarker and demonstrates that combining distinct measurements of biological ageing further helps to determine risk of age-related deterioration and death.
| S-EPMC5984097 | biostudies-literature