Aging & Longevity

Partial reprogramming has emerged as a promising strategy to reset the epigenetic landscape of aged cells towards more youthful profiles. Recent advancements have included the development of chemical reprogramming cocktails that can lower the epigenetic and transcriptomic age of cells and upregulate mitochondrial biogenesis and oxidative phosphorylation. However, the ability of these cocktails to affect biological age in a mammalian aging model has yet to be tested. Here, we have characterized...

The geroscience hypothesis suggests that understanding mechanisms underlying aging will enable us to delay and lessen age-related disability and diseases. The role of mechanical factors has been increasingly appreciated in many aspects of the aging process. Here, we use mouse models to investigate changes in the biomechanics of the proximal pulmonary artery, lung function, and right ventricle function in aging. We found an age-related decreased capacity to store energy and increased...

CONCLUSIONS AND IMPLICATIONS: This study demonstrates that multiple falls are a significant predictor of future dementia and highlights the importance of fall frequency. Recurrent falls may serve as a potential clinical marker for identifying individuals at higher risk. Clinicians should maintain heightened vigilance for cognitive decline in middle-aged and older adults with a history of recurrent falls to facilitate early detection of dementia. Given the limited evidence base and high...

Cognitive and psychiatric comorbidities are among the most persistent and disabling challenges experienced by children and adults with epilepsy, with serious implications for daily functioning, health-care utilization, long-term social outcomes and quality of life. Traditionally, research has focused on epilepsy-specific biological risk factors, such as seizure frequency or epilepsy syndrome, but growing evidence indicates that non-medical factors also shape neurodevelopmental, cognitive and...

CONCLUSION: Trajectories of total depressive symptoms marked by escalation, instability, or sustained elevation exhibited significantly elevated stroke risk. In contrast, individuals displaying decreasing depressive symptoms exhibit stroke risk comparable to those maintaining consistently low levels. Specifically, an ascending trajectory of cognitive-affective symptoms, alongside unstable and persistently elevated trajectories of somatic symptoms, are linked to increased stroke risk. These...

CONCLUSION: This study provides the first integrative single-cell transcriptomic map of microglial-myeloid interactions after TBI across multiple tissues and time points, linking microglial signaling to mitochondrial dysfunction and neuroinflammation. These findings lay the foundation for therapeutic strategies targeting myeloid-driven immune regulation in TBI.

Neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD) are among the most significant health challenges of aging, characterized by progressive cognitive and motor decline. Increasing evidence suggests that these conditions are not inevitable outcomes of aging but may instead be driven by preventable mechanisms involving oxidative stress, chronic inflammation, and disruptions in homeostasis. This manuscript proposes a preventive framework that integrates...

Neuronal aging and neurodegenerative diseases are accompanied by proteostasis collapse, while the cellular factors that trigger it have not been identified. Impaired mitochondrial transport in the axon is another feature of aging and neurodegenerative diseases. Using Drosophila, we found that genetic depletion of axonal mitochondria causes dysregulation of protein degradation. Axons with mitochondrial depletion showed abnormal protein accumulation and autophagic defects. Lowering neuronal ATP...

White matter degeneration in aging drives cognitive and motor decline. Oligodendrocytes (OLs) and their precursors are central to this process. Their intrinsic aging, marked by differentiation failure, metabolic and mitochondrial deficits, and transcriptional epigenetic dysregulation, causes myelin thinning and axonal support loss. Degeneration is amplified by dysfunctional crosstalk: microglia clear debris poorly and turn inflammatory; astrocytes disrupt lipid balance and secrete inflammatory...

Lysosomes are responsible for clearing cellular waste and facilitating material recycling, thus playing a crucial role in maintaining cellular homeostasis and even in resisting the development of various diseases. Lysosomes are highly dynamic organelles. While typically exhibiting a vesicular morphology, lysosomes can remodel into tubular structures under specific conditions; this morphological plasticity underpins their functional complexity. Aging triggers significant lysosomal morphological...

CONCLUSIONS: Avoiding increases in perceived social exclusion could encourage the decision to donate, an important prosocial behavior, pending further longitudinal evidence. Cross-country comparisons are recommended.

CONCLUSIONS: In this study, we explored the association between ALM or sarcopenia and multiple health outcomes, highlighting the widespread impact of ALM on systemic health condition. These findings provide new epidemiological evidence on how ALM or sarcopenia influence the health status among the U.S.

N⁶-methyladenosine (m⁶A) orchestrates RNA fate decisions through a dynamic interplay of writers, erasers, and readers, modulating splicing, stability, and translation. This review unveils how m⁶A fine-tunes senescence-associated pathways (p53/p21, p16-RB) with cancer-context-dependent duality-either as a tumor suppressor or promoter of progression/resistance. Leveraging single-cell and spatial omics, we dissect m⁶A's spatiotemporal heterogeneity in tumor-immune ecosystems. We consolidate...

Cardiovascular diseases (CVDs), including hypertension, heart failure, atherosclerosis and myocardial infarction, remain the leading cause of morbidity and mortality worldwide. Aging is a predominant risk factor for CVD. Cardiovascular aging is characterized by progressive structural changes at the cellular level and functional decline within the cardiovascular system, ultimately contributing to the onset and progression of CVD. These changes include alterations in left ventricular (LV) systolic...

CONCLUSIONS AND IMPLICATIONS: Chronic pain, especially its intensity, is independently associated with reduced physical performance in older adults. These findings reinforce the need for primary care services to prioritize the identification and management of chronic pain to help preserve mobility and functional capacity in aging populations.

Decelerating gains in life expectancy (e(0)) in high-income countries have raised concerns about the future of human longevity. To enhance our understanding of these developments, we examine subnational (N = 450) mortality trends in Western Europe in the period 1992-2019. Between 1992 and 2005, gains in life expectancy were both substantial and widespread. Laggard regions experienced the fastest improvements, yielding rapid regional convergence. Between 2005 and 2019, however, gains in these...

Hypertension prevalence is increasing in both aging and younger populations, with high salt intake being a key environmental driver. Whether young and aged individuals exhibit similar physiological and molecular responses to salt loading remains unclear. This study compared hemodynamic and renal redox adaptations to salt loading in young (8-week) and aged (50-week) Dahl salt-sensitive (DSS) rats. Both groups developed salt-sensitive hypertension, but blood pressure (BP) elevation was markedly...

Physical and cognitive interventions, alone or combined, are recognized strategies to enhance cognitive function in healthy older adults, though their relative effectiveness remains debated. This study aimed to compare and classify the impact of such interventions on cognitive performance. Following PRISMA guidelines, randomized controlled trials (RCTs) were identified through searches of PubMed, Web of Science, and Scopus, with screening and data extraction procedures guided by the Cochrane...

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