Aging & Longevity

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...

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.

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.

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...

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 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...

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...

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...

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, +...

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...

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...

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.

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 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...

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.

Frailty, a clinical syndrome of multisystem decline and homeostatic vulnerability, is a critical public health priority. While the gut microbiome regulates immune and metabolic signaling, current evidence remains fragmented. We performed a metagenomic meta-analysis of 955 individuals from 28 independent cohorts across 24 countries to identify universal microbial signatures and develop a generalizable discriminative model. Frailty was determined using a Proxy Frailty Index based on the deficit...

CONCLUSION: High-intensity aerobic exercise increased serum zonulin more than low-intensity exercise in older adults, suggesting differential effects on intestinal barrier-related responses. Although inflammatory markers tended to improve more with high-intensity exercise, these findings should be interpreted cautiously. Individualized exercise prescription may be needed when considering effects on intestinal barrier function in older adults.

CONCLUSION: Our integrative study demonstrates that aging-induced SPARCL1 deficiency in brain endothelial cells causally contributes to VaD pathogenesis. These findings highlight SPARCL1 as a mechanistically grounded and therapeutically promising target for VaD.

Telomere-driven replicative crisis transforms the architecture of the evolving cancer genome, yet the mechanisms and consequences remain incompletely resolved, with potential biomarkers undiscovered. To address this, we have employed novel tools and methodologies to explore a human fibroblast model of crisis using high resolution multi-omics analyses. We have developed a unique chromatin conformation capture procedure for identifying distant genomic loci that interact with eroding telomeres,...

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