Aging & Longevity
Therapeutic inhibition of telomeric DNA damage response rescues hematopoietic dysfunction driven by telomere shortening and aging
Telomeres progressively shorten and accumulate damage with aging, and this contributes to cellular senescence and hematopoietic dysfunction. We previously showed that telomere dysfunction induces synthesis of telomeric noncoding RNAs required for activation of the telomeric DNA damage response (tDDR), a driver of senescence and inflammation. However, whether the tDDR causally impairs hematopoiesis remained unclear. Here we show in telomerase-deficient Terc^(-/-) mice, which recapitulate...
(In)congruence effect of chronological age and subjective age on older adults' cognitive functioning: the moderating role of social participation and cross-cultural comparisons
CONCLUSIONS: These findings provide novel evidence for the interactive effects of objective and subjective age, psychosocial resources, and cultural context on cognitive aging, highlighting the potential importance of age perceptions and social participation in cognitive aging.
The joint association of sleep duration and physical activity with frailty among older adults: the first evidence from CHARLS
CONCLUSIONS: The findings of this study demonstrate that adequate sleep duration and PA are crucial independent and synergistic protective factors against rapid frailty progression. These findings highlight that concurrently targeting both behaviors is a vital clinical strategy to mitigate severe frailty and promote healthy aging.
Multidimensional health profiles and cognitive function of community-dwelling older adults: a latent profile analysis
CONCLUSIONS: This study highlights the importance of multidimensional health profiles in understanding cognitive vulnerability among older adults. The identified patterns of co-occurring physical and psychosocial symptoms highlight the importance of adopting holistic, tailored strategies to support cognitive health. Developing profile-specific interventions addressing physical function, symptom management, and psychosocial well-being is essential for preventing cognitive decline in this...
The components and effects of home rehabilitation on activities of daily living and physical performance of community dwelling older people with low physical performance - a systematic review and meta-analysis of randomized controlled trials
CONCLUSION: Home rehabilitation comprises three main intervention approaches. The Activity-based and Exercise-based yield small improvements in BADL and physical performance. Evidence for other ADL outcomes and the Reablement-based remains limited.
Effects of aging on recognition and dominance perception in laughter
INTRODUCTION: Aging is associated with reduced accuracy in recognizing others' emotions, an ability that is important for maintaining social connectedness in later life. Laughter is a social signal with multiple functions, as it can facilitate social bonding but also convey negative social meanings, for example when directed at someone. In previous research we have shown that younger adults are able to classify spontaneously emitted joyful, schadenfreude, and tickling laughter above chance...
Association Between Depressive Symptoms and Physiological Risk Factors for Falls
CONCLUSION: Conclusion: Fallers presented more depressive symptoms, morbidities, polypharmacy, and worse subjective health status. Depressive symptoms do not act directly over the number of falls; nonetheless, those with depressive symptoms presented a higher chance of falling, which may be associated to slower reaction time. Psychological symptoms play an important role in falls, and should, therefore, be considered in identifying older people at risk and in developing prevention programs.
Digital Technologies for Healthy Longevity: A Policy Agenda from the Einstein Circle on Inclusive, Data-Driven Ageing Societies
BACKGROUND: Rapid population ageing presents one of the defining global health challenges of the twenty-first century. While digital technologies are increasingly used to support older adults, their deployment often remains fragmented, inequitable, and insufficiently guided by ethical and legal frameworks. This paper proposes an integrated policy agenda for healthy longevity, based on the interdisciplinary work of the Einstein Circle Longevity - Healthy Ageing Assisted by Digital Technologies.
Bidirectional Relationship and Shared Mechanisms Between Sarcopenia and Osteoporosis: An Observational Study Integrating Genomic, Proteomic, and Metabolomic Data
With global population aging, sarcopenia and osteoporosis have become critical public health challenges. Muscles and bones are closely interconnected anatomically and functionally, but the biological mechanisms connecting sarcopenia and osteoporosis have not yet been fully elucidated. This study systematically investigated the bidirectional relationship and shared mechanisms between sarcopenia and osteoporosis through multi-omics analysis integrating genomic, proteomic, and metabolomic data from...
Role of Klhl14 in senescence and epithelial-to-mesenchymal transition via TGF-beta modulation
KLHL14, a component of an E3-ubiquitin ligase complex, has emerged as a context-dependent oncogene or tumor suppressor, particularly important for thyroid development. Yet its role in thyroid biology remains largely unexplored. In this study, we uncover a central function for KLHL14 in maintaining thyroid epithelial identity and regulating tissue homeostasis. Using a thyroid organoid model, we show that KLHL14 is essential for the proper growth and maturation of thyroid cells. Reduction of...
Age-related changes in behavioural and neural variability in a decision-making task
Age-related cognitive decline in learning and decision-making may arise from increased variability of neural responses. Here, we investigated how ageing affects behavioural and neural variability by recording >18,000 neurons across 16 brain regions (including cortex, hippocampus, thalamus, midbrain, and basal ganglia) in younger and older mice performing a visual decision-making task. Older mice showed more variable response times, reproducing a common finding in human ageing studies. Ageing...
Lineage tracing from cellular heritage to disease destiny
The developmental history of a cell fundamentally defines its identity and function. Recent advances in cell lineage tracing now enable high-resolution reconstruction of cellular ancestries in vivo, illuminating how lineage dictates fate in health and disease. This Review highlights recently developed tools, ranging from refined recombinase systems to advanced synthetic and natural barcoding approaches, that facilitate the investigation of pathological lineage programs in cancer, cardiovascular...
Tau protein as a regulator of mitochondrial function and dynamics
Mitochondrial damage is a shared hallmark of brain aging and neurodegeneration. While pathological Tau mutations disrupt mitochondrial dynamics and function, the physiological role of wild-type (WT) Tau in the maintenance of mitochondrial homeostasis remains poorly understood. Here, using Caenorhabditis elegans and mice lacking PTL-1, the nematode Tau-like homolog, and Tau respectively, we demonstrate that Tau deficiency promotes a shift toward a pro-fusion mitochondrial state associated with...
The influence of aging on graded peripheral venous return and complex blood flow features through human veins
Aging is associated with reduced venous compliance and altered muscle pump function, though how these features impact venous return during volume-stressed conditions remains poorly characterized. We examined lower-limb venous flow dynamics and muscle pump efficiency between healthy younger (YA) and older adults (OA) under two volume-stressed conditions. Fourteen YA (7F, 26 ± 4 years) and fourteen OA (9F, 76 ± 6 years) underwent assessments at head-down tilt (HDT, -3°) and head-up tilt (HUT, +...
A Gut-Centric View of Ageing: A Pilot Analysis Mapping Age-Associated Immune and Molecular Alterations in Colonic Mucosa Using Spatial Proteomics
Investigating age-associated changes in intestine and understanding immune-related intestinal dysfunctions is essential for promoting healthy ageing. Mucosal surfaces represent a distinct immune compartment enriched with specialised lymphocytes that interact dynamically with the epithelial layer. In this study, we present novel spatially resolved insights into the cellular and molecular alterations in the ageing murine gut mucosa. Our findings reveal a complex network of interdependent...
Clonal Analyses Reveal the Impact of Hematopoietic Stem and Progenitor Cell Aging on T Cell Development
T cell output from the thymus falls throughout life and is associated with profound remodeling of the thymic stroma. To what extent the decline in T cell output is caused by aging of the hematopoietic stem and progenitor cells (HSPCs) has been difficult to define because of HSPC heterogeneity, the multi-stage process of HSPC migration, and the cross-talk between hematopoietic and stromal elements of the thymus. To address the contribution of HSPC aging on T cell development, we interrogated T...
High-saturated-fat diet drives female-biased neurodegeneration in <em>Drosophila</em> via oxidative stress and impaired autophagic flux
CONCLUSION: These findings identify oxidative stress and disrupted autophagy as key mediators of saturated-fat-induced neuronal decline and highlight a sex-specific vulnerability to dietary fat composition. This work establishes Drosophila as a powerful model for dissecting nutritional drivers of neural aging and suggests that metabolic stress pathways represent critical early targets in diet-associated neurodegeneration.
Engagement with the national electronic health records by people with Parkinson's disease
CONCLUSIONS: Personal EHR engagement among the vulnerable aging population is influenced by a complex interplay of patient, HCP, and technology-related factors, which must be addressed holistically to ensure inclusive usage and adherence to digital health tools.
Age-related differences in motor learning, sensorimotor neurochemistry, and cortical reactivity co-occur but are dissociated
Age-related declines in motor learning are commonly attributed to changes in sensorimotor neurophysiology. However, direct links between neurochemistry, electrophysiology, and behavior are scarce. Here, we investigated whether age-related differences in GABAergic inhibition and cortical reactivity mediate age-related simple and complex motor learning declines. To do so, we employed magnetic resonance spectroscopy (MRS) and transcranial magnetic stimulation-electroencephalography (TMS-EEG) in...
The joint association of biological aging and dietary oxidative balance score with cardiometabolic multimorbidity among U.S. older adults
CONCLUSIONS: Low DOBS and accelerated PhenoAge were jointly associated with a higher likelihood of CMM among U.S. older adults, highlighting the potential relevance of dietary oxidative balance and biological aging in cardiometabolic multimorbidity.
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