Aging & Longevity

INTRODUCTION: In an increasingly aging society, testing hippocampal-dependent cognition in a quick and low resource manner will be crucial in: assessing the potential benefits of lifestyle choices and interventions affecting cognitive ageing (such as those involving exercise, diet, and sleep); detecting pathological aging, such as in Alzheimer's disease, where hippocampal degeneration occurs relatively early on.

Age-related deterioration in postural control is an important factor decreasing quality of life. Functional neuroimaging studies have shown that the activation of the prefrontal cortex (PFC) during balancing is typically higher in older (OA) compared to younger adults (YA), probably reflecting a mechanism contributing to worsened balance control with aging. Here, we hypothesized that balance training (BAL) shifts PFC activation towards a more efficient pattern, enabling improved balance...

INTRODUCTION: Differences in lifestyle factors contribute towards inequalities in dementia incidence and memory trajectories across racial and ethnic groups. We identifieded lifestyle risk factors that best discriminat memory trajectories in older adults without cognitive impairment.

Cellular senescence is a conserved cellular program characterized by a permanent cell cycle arrest triggered by a variety of stressors. Originally described as a tumor-suppressive mechanism, it is now recognized to exert pleiotropic and context-dependent functions, contributing to key physiological processes such as embryogenesis and tissue repair, as well as to processes associated with aging and the development of age-related diseases. Unlike normal cells, senescent cells remain metabolically...

Resistance to age-related pathological changes (brain maintenance), including Alzheimer's disease, cerebrovascular disease, and neurodegeneration may promote cognitive resilience in aging. However, how lifestyle and health profiles relate to successful cognitive and brain aging remains poorly understood. In a novel, deeply phenotyped cohort of 211 cognitively unimpaired older adults (age = 71.0 ± 7.4 years, 46% female), we characterized principal components of lifestyle and health using...

CONCLUSION: Better diet quality, reflected by higher HEI scores, is associated with a lower prevalence of sarcopenia in older adults, highlighting the importance of nutrition in preventing sarcopenia.

The hippocampus (Hc), which is crucial for memory across the lifespan, is comprised of distinct subfields: dentate gyrus (DG), Cornu Ammonis (CA) sectors 1-3, and subiculum. Cross-sectional studies show that Hc subfield volumes exhibit a differential association with age across the lifespan. However, the evidence of age-related changes and individual variability in developmental trajectories is sparse. We examined changes in Hc subfield volumes in a large normative lifespan sample (N = 474 at...

The gradual decline in physiological functions that comes with aging contributes to a range of chronic diseases, such as Alzheimer's, type 2 diabetes, heart failure, and osteoarthritis. Significant advancements in human longevity due to socioeconomic development have resulted in a foreseeable and substantial strain on the global healthcare system. In fact, there is now a shift in research focus towards enhancing healthspan. As a result, the development of improved therapies for various chronic...

Age-related iron accumulation is widely observed in various species and significantly impacts physiological processes. However, systematic investigation into how age-related iron dysregulation affects different life traits is still limited. This study utilizes the model organism C. elegans to examine the roles of iron regulatory genes throughout different life stages, focusing on their effects on iron homeostasis, longevity, mobility, size, and mechanosensation. Our expression analysis indicated...

Cellular senescence is a hallmark of organismal aging but how it drives aging in human tissues is not fully understood. Here we leverage single nucleus multiomics to profile senescence in mononucleated cells of human skeletal muscle and provide the first senescence atlas. We demonstrate the intra- and inter-populational transcriptomic and epigenomic heterogeneity and dynamics of cellular senescence. We also identify commonalities and variations in senescence-associated secretory phenotypes...

CONCLUSION: Sarcopenia can serves as a significant predictor of long-term mortality in centenarians and functions as an important independent predictor.

CONCLUSIONS: In addressing apathy, it is important to check for the co-occurrence of depression, life satisfaction, and the availability and utilization of social support.

CONCLUSION: The biographical intervention effectively reduced ageism among CCU nurses. Increased knowledge of the various dimensions of older adults' lives seems to have positively influenced nurses' attitudes and fostered appropriate interactions, ultimately facilitating care and treatment. TRIAL REGISTRATION: The article was registered by the Iranian Registry of Clinical Trials under number IRCT20220522054956N1, date of registration 2022/07/02.

Hematopoietic stem cells (HSCs) with mutations that can cause clonal hematopoiesis of indeterminate potential (CHIP) accumulate during aging. Agarwal et al.¹ demonstrate in Nature that intestinal barrier permeability increases with age and enables the microbial metabolite ADP-heptose to reach the bone marrow, thus driving the expansion of DNMT3A-mutant HSCs.

Epigenome-wide association studies (EWASs) are transforming our understanding of the interplay between epigenetics and complex human traits. We introduce the methylation screening array (MSA) to enable scalable and quantitative screening of trait-associated DNA cytosine modifications in large human populations. The MSA integrates EWASs and cell-type-linked methylation signatures, covering diverse traits and diseases. Using the MSA to profile the ternary-code DNA methylations-dissecting...

Disseminated tumor cells (DTCs) can remain in a non-proliferative, dormant state for years in distant organs, but the exogenous causes triggering their reactivation and metastatic colonization are unclear. Here, we demonstrate that chemotherapeutic drugs, including doxorubicin and cisplatin, enhance proliferation and lung metastasis of dormant breast cancer cells. Using a recombinase-based dormancy tracing system, DormTracer, we confirm chemotherapy-induced reactivation of dormant DTCs leading...

BRAF and MEK inhibitors (BRAF/MEKi) have radically changed the treatment landscape of advanced BRAF mutation-positive tumours. However, limited efficacy and emergence of drug resistance are major barriers for successful treatments. Here, by using relevant preclinical models, we find that Connexin43 (Cx43), a protein that plays a role in cell-to-cell communication, enhances the effectiveness of BRAF/MEKi by recruiting DNA repair complexes to lamin-associated domains and promoting persistent DNA...

Taurine is a conditionally essential nutrient and one of the most abundant amino acids in humans, with diverse physiological functions. The cellular uptake of taurine is primarily mediated by the taurine transporter (TauT), and its dysfunction leads to retinal regeneration, cardiomyopathy, neurological and aging-associated disorders. Here we determine structures of TauT in two states: the apo inward-facing open state and the occluded state bound with substrate taurine or γ-aminobutyric acid...

Mobility is a cornerstone of health and quality of life, particularly in older adults. Digital mobility outcomes (DMOs) from real-world walking data offer crucial insights into the functional status and early markers of mobility decline. This study provides reference values for walking activity, pace, rhythm, and gait bout-to-bout variability in community-dwelling older adults and evaluates the effects of age, sex, height, and weight on these parameters. Using data from 200 older adults (aged...

We constructed a polygenic protective score specific to Alzheimer's disease (AD PPS) based on the current literature among the participants enrolled in five studies of healthy aging and extreme longevity in the USA, Europe, and Asia. This AD PPS did not include variants on apolipoprotein E (APOE) gene. Comparisons of AD PPS in different data sets of healthy agers and centenarians showed that centenarians have stronger genetic protection against AD compared to individuals without familial...