Aging & Longevity
Future heat-related mortality in Europe driven by compound day-night heatwaves and demographic shifts
Anthropogenic climate change is driving summer heat toward more humid conditions, accompanied by more frequent day-night compound heat extremes (high temperatures during both day and night). As the fast-warming and aging continent, Europe faces escalating heat-related health risks. Here, we projected future heat-related mortality in Europe using a distributed lag nonlinear model that incorporates humid heat and compound heat extremes, strengthened by a health risk-based definition of extreme...
ApaH decaps Np<sub>4</sub>N-capped RNAs in two alternative orientations
Enigmatic dinucleoside tetraphosphates, known as 'alarmones' (Np(4)Ns), have recently been shown to function in bacteria as precursors to Np(4) caps on transcripts, likely influencing RNA longevity and cellular adaptation to stress. In proteobacteria, ApaH is the predominant enzyme that hydrolyzes Np(4)Ns and decaps Np(4)-capped RNAs to initiate their 5'-end-dependent degradation. Here we conducted a biochemical and structural study to uncover the catalytic mechanism of Escherichia coli ApaH, a...
Oxytocin Enhances Demethylation Through TET Enzyme Expression in Neurons of Aged Mice: Oxytocin as a Potential Antiaging Peptide
While it is well-documented that plasma oxytocin (OXT) levels decline with age, the underlying mechanisms remain elusive. This study aimed to elucidate the physiological mechanisms contributing to this age-related decrease in plasma OXT and the possible use of OXT supplementation on improving age-related decline of neural function. Comparing young (9 weeks) and aged (> 45 weeks) mice, aged mice showed reduced plasma OXT levels, an increase in the inflammation marker hs-CRP, and decreased...
Sustained benefits of long-term biochar application for food security and climate change mitigation
Biochar application offers significant potential to enhance food security and mitigate climate change. However, most evidence stems from short-term field experiments (≤3 y), leaving uncertainty about the long-term sustainability of these benefits, especially with annual biochar additions to soils. To address this knowledge gap, we analyzed a global dataset from 438 studies (3,229 observations) and found that long-term annual biochar application (≥4 y) not only sustains but often enhances its...
Searching for a Potential Blue Zone in the Nordics: A Study on Differences in Lifestyle and Health in Regions Varying in Longevity in Western Finland
To delay social and healthcare utilisation among the ageing population, there is an increasing focus on the role of health-promoting lifestyle adopted at an individual and/or community level. Longevity is generally viewed as the ultimate outcome of health, although a high life expectancy does not necessarily go together with health and/or a health-promoting lifestyle. The potential coherence between longevity, health and lifestyle may vary in different cultural, political, social and economic...
Hexokinase regulates Mondo-mediated longevity via the PPP and organellar dynamics
The transcriptional complex Mondo/Max-like, MML-1/MXL-2, acts as a convergent transcriptional regulatory output of multiple longevity pathways in Caenorhabditis elegans. These transcription factors coordinate nutrient sensing with carbohydrate and lipid metabolism across the evolutionary spectrum. While most studies have focused on the downstream outputs, little is known about the upstream inputs that regulate these transcription factors in a live organism. Here, we found that knockdown of...
Associations of Skin Biomechanical Properties With Biological Aging Clocks and Longitudinal Changes in Intrinsic Capacity in Adults Aged 20-93: The INSPIRE-T Project
Evidence connecting skin aging to functional decline and systemic aging biomarkers is lacking. This study investigated how skin-aging biomechanics were associated with changes in intrinsic capacity (IC), a marker of healthy aging. We also explored their links with biological aging clocks (epigenetic and inflammatory clocks) and potential moderating effects on the skin-IC relationship. Baseline skin elasticity and viscoelasticity were measured in 441 INSPIRE-T participants aged 20 to 93 (59.9%...
The role of hemoglobin/red cell distribution width value in predicting early major adverse events after open heart surgery in elderly patients
CONCLUSION: In this study, we showed for the first time in the literature that the HRR value calculated from preoperative blood values is a key predictor for in-hospital MAE. In these patients, the HRR value can be used as a preoperative risk biomarker.
Analysis of variability and epigenetic age prediction across microarray and methylation sequencing technologies
Using 100 technical replicate samples from two adult buccal cohorts, we compared technical methylation variability and signal strength between the Infinium MethylationEPIC v2.0 array and the Twist Human Methylome Panel across 753,648 shared CpGs. Twist methylation sequencing showed skewed methylation distributions and fewer highly correlated CpGs than MethylationEPIC arrays. Variance analysis revealed a skew toward higher signal strength in MethylationEPIC datasets, with a subset of CpGs showing...
Efficacy of progressive resistance training intensities and adequate dietary protein intake for community-dwelling frail older adults (TEAMS study), protocol for a randomised controlled trial
BACKGROUND: Progressive Resistance Training (PRT) and adequate dietary protein are crucial for preventing and managing sarcopenia and frailty in older adults. To date, the optimal intensity of PRT and the added value of dietary protein for enhancing muscle mass, strength, and physical performance in frail older adults remain unclear. This randomised controlled trial aims to determine the efficacy of various PRT intensities and adequate dietary protein intake in improving muscle mass, strength...
Advancements in the investigation of the mechanisms underlying cognitive aging
Cognitive aging, a pivotal domain at the intersection of neuroscience and psychology, exhibits a strong association with neurodegenerative disorders; however, its comprehensive underlying mechanisms remain incompletely elucidated. This review aims to provide a thorough synthesis of recent advancements in the investigation of cognitive aging in the brain, highlighting multidimensional assessment techniques, neurobiological foundations, molecular regulatory pathways, systemic changes,...
Cardiovascular inflammaging: Mechanisms, consequences, and therapeutic perspectives
Both aging and systemic inflammation are major risk factors for cardiovascular disease. This review summarizes the interrelationship of aging and inflammation-known as inflammaging-and the consequences for cardiovascular health. We discuss mechanisms including epigenetic modification, mitochondrial dysfunction, cellular senescence, and gut dysbiosis, many of which are themselves interrelated. Increasing understanding of inflammaging provides an array of biomarkers, some of which are now...
Pathogens accelerate features of human aging: A review of molecular mechanisms
Many models of aging assume that processes such as cellular senescence or epigenetic alteration occur under sterile conditions. However, humans sustain infection with viral, bacterial, fungal, and parasite pathogens across the course of a lifetime, many of which are capable of long-term persistence in host tissue and nerves. These pathogens-especially members of the human virome like herpesviruses, as well as intracellular bacteria and parasites-express proteins and metabolites capable of...
Group-based trajectory modelling for cognitive changes in middle-aged and older adults: A systematic review
CONCLUSION: A substantial proportion of aging individuals maintain cognitive function over time, which may be supported by protective strategies like cognitive/physical engagement, healthy sleep, social connection, and disease management. The adverse outcomes linked to decline trajectories underscore the need for future research on modifiable factors. Comparing predictors across subgroups provides insights into cognitive resilience and proactive protection. Further exploration of biological...
Modeling the geometry of circadian synchronization and period across aging
Circadian freerunning periods change across the lifespan, yet most computational models do not reproduce these shifts without assuming additional mechanisms. Although the maturation and later deterioration of the suprachiasmatic nucleus (SCN) shape behavioral and humoral rhythms, the underlying driver of period change is more general. We show that it arises from an inherent property of a positively skewed frequency distribution, which naturally follows from a symmetric Gaussian distribution of...
Profiling with senescence-associated secretory phenotype score identifies GDC-0879 as a small molecule sensitizing glioblastoma to anti-PD1
Senescence-associated secretory phenotype (SASP) in cancer refers to the bioactive secretome produced by senescence cells in the tumor microenvironment, which could be triggered by therapeutics or local stress conditions. Here, we provided a SASP Score in glioblastoma (GBM) with generating a SASP gene panel to identify the potential small molecular candidate targeting SASP in GBM. The effectiveness of this scoring method was firstly interrogated with our in-house GBM cohort and public datasets,...
Glial reactivity and cognitive decline follow chronic heterochromatin loss in neurons
In aging cells and animal models of premature aging, heterochromatin loss coincides with transcriptional disruption including the activation of normally silenced endogenous retroviruses (ERVs). Here we show that loss of heterochromatin maintenance and de-repression of ERVs result in a chronic inflammatory environment characterized by neurodegeneration and cognitive decline in mice. We identify distinct roles for HP1 proteins to ERV silencing where HP1γ is necessary and sufficient for H4K20me3...
Epigenetic dysregulation of transposable elements in cognitive impairment and Alzheimer's disease
Aging and cognitive impairment increase the risk for Alzheimer's disease (AD), and growing evidence suggests that transposable elements (TEs) in the genome play a role in aging and AD. The mechanisms of TE dysregulation in this context are unclear, but one possibility is that epigenetic changes, including DNA hypomethylation and/or reduced chromatin structure, underlie age- and AD-related TE activity. Therefore, the purpose of the present study was to generate a resource for studying TE...
Association between weight-adjusted waist index and cardiometabolic multimorbidity in older adults: Findings from the English Longitudinal Study of Ageing
The weight-adjusted waist index (WWI) is a novel anthropometric measure designed to better reflect central obesity than traditional indices such as body mass index and waist circumference (WC). This study examined the prospective association between WWI and cardiometabolic multimorbidity (CMM) and evaluated its predictive utility. We included 3,348 participants (mean age 63 years; 45.1% male) from the English Longitudinal Study of Ageing who were free from hypertension, coronary heart disease,...
The National Dementia Workforce Study: Methods for Surveying Community Clinicians Who Provide Care to People With Dementia
People with dementia have complex medical, functional, and social needs and experience highly variable care quality and outcomes across the U.S. health care system. Community-based physicians, nurse practitioners, and physician assistants serve critical roles in diagnosing and managing dementia, yet little is known about this workforce and factors contributing to variability in care. The National Dementia Workforce Study (NDWS), sponsored by the National Institute on Aging, is conducting large...
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