Aging & Longevity

Skeletal muscle atrophy and weakness resulting from loss of motor neuron innervation are shared hallmarks of amyotrophic lateral sclerosis (ALS) and age-associated sarcopenia. However, muscle wasting in ALS is rapid and severe, whereas sarcopenia progresses gradually over decades, peaking at an advanced age. The molecular mechanisms underlying muscle wasting in these conditions remain incompletely defined. Here, we used the SOD1^(G93A) ALS mouse model and wild-type mice across the lifespan to...

Defects in crystals are usually considered to be consequences of deformation, but they can also be engineered as strengthening features. Planar defects can strengthen structural alloys but usually form only during deformation or service, limiting control over their density, stability, and chemistry. We show that predeformation followed by aging can convert such defects into a designed architecture of ordered defect phases. In a single-crystal cobalt-nickel-based superalloy and a polycrystalline...

Every cell in the human body carries its own genome, shaped by mutations acquired over a lifetime, yet this vast somatic variation has been nearly impossible to measure. The SMaHT Network now delivers benchmarked tools and the first body-wide map of somatic mosaicism, establishing a baseline of "normal" against which its roles in development, aging, and disease can finally be tested.

CONCLUSION: In this analytic NHATS sample, self-reported chewing or swallowing problems were not independently associated with a statistically significant difference in episodic-memory trajectory after sensory and other prespecified adjustment. The item may warrant oral, swallowing, functional, or neurological assessment, but it is not a specific marker of masticatory dysfunction or cognitive risk.

CONCLUSION: Cortical alpha slowing was detected in PD and MSA-C, but not in MSA-P. Age independently contributes to alpha slowing and strengthens its association with non-motor symptom burden, supporting age-aware interpretation of resting-state electroencephalography biomarkers in synucleinopathies.

CONCLUSION: These findings provide initial evidence for a candidate kinematic index of motor reserve in healthy aging. Motor reserve was not reducible to global motor speed or chronological age but expressed as a multidimensional profile of timing stability, lateralized motor organization, and consistency across task contexts.

Normal aging compromises behavioral functions supported by cortical circuits, yet how age-related cellular reorganization relates to weakened circuit-behavior correspondence remains poorly defined. Here, we examined layer 4 (L4) of the mouse primary somatosensory barrel cortex, a thalamorecipient lamina in which dendritic organization, microglial process architecture, and whisker-dependent tactile function can be analyzed within the same sensory system. Aged mice showed impaired...

CONCLUSION: Age-friendly work requires shared responsibility across societal actors, supported by clear coordination. Personal relationships and informal networks should be recognised as valuable for enabling collaboration, but they need to be complemented by formal structures to ensure sustainability over time. Moreover, greater efforts to reach seldom-heard older adults are needed. Doing so may contribute to more nuanced and age-friendly initiatives that better reflect the diverse needs of the...

CONCLUSIONS AND IMPLICATIONS: Perceived CC and technology use characterized cognitively robust older adults, whereas tangible support identified vulnerable individuals yet was associated with slower cognitive decline. These findings underscore the need for nuanced CC strategies: digital tools engage those aging well, while intensive tangible support may be especially important for those with greater vulnerabilities. These associations are observational and do not establish causality.

Aged skeletal muscle has a reduced ability to adapt to hypertrophic stimuli concomitant with dysregulation across several molecular layers. Whether altered RNA splicing associates with impaired adaptive potential is not well studied. We hypothesized that aging disrupts the splicing response to involuntary muscle mechanical loading. Using deep short-read Illumina RNA-sequencing (SRS, 60 million read pairs) and third generation Oxford Nanopore long-read RNA-sequencing (LRS) combined with a murine...

Skeletal muscle is increasingly recognized as a secretory organ that communicates with distant tissues through the release of bioactive factors, including extracellular vesicles (EVs). During aging, muscle-derived EVs have emerged as important mediators of interorgan communication, influencing tissue homeostasis, regeneration, metabolism, and disease progression. Recent studies demonstrate that skeletal muscle EVs carry diverse cargos such as proteins, lipids, metabolites, and regulatory RNAs...

CONCLUSIONS: Using a community-engaged modified Delphi approach, this study identified key clinical and research priorities for older transgender adults. Findings highlight the importance of provider knowledge, social support, and addressing knowledge gaps in gender-affirming care and aging. These results provide direction for future research and best practice guidelines for this population.

An elevated NADH/NAD^(+) ratio (NADH-reductive stress) is a hallmark of mitochondrial dysfunction, yet how it drives pathologies ranging from primary mitochondrial disorders to ageing remains poorly understood^(1,2). Here, we show that mitochondrial respiratory chain inhibition in primary human fibroblasts induces NADH-reductive stress that coexists with profound NADPH depletion. Using the Escherichia coli soluble transhydrogenase (EcSTH)³ to model this redox coupling in cells with intact...

Rheumatoid arthritis (RA) is an autoimmune disease marked by joint and systemic inflammation. Anticitrullinated protein antibodies identify an at-risk stage that precedes clinical RA, yet the mechanisms driving disease progression remain poorly understood. Here we show that anticitrullinated-protein-antibody-positive individuals who progressed to RA exhibited a marked expansion of CXCR5^(+)CD69^(+)-activated naive B cells (aNAVs) before disease onset. These cells displayed inflammatory and...

Age-related cognitive decline is associated with altered inhibitory signaling in hippocampal circuits, but the mechanisms underlying this dysfunction remain incompletely understood. Neural stem cells (NSCs) persist in the adult hippocampus and influence brain function beyond generating new neurons, although the molecular signals involved remain unclear. Here we show that phospholipase A2 group VII (PLA2G7), a secreted lipid-metabolizing enzyme expressed in NSCs, negatively regulates inhibitory...

Aging is characterized by progressive functional decline accompanied by distinct transcriptomic and epigenetic alterations. Although partial reprogramming via Yamanaka factors can reverse these signatures and improve cell function, toxicity and efficacy concerns limit their in vivo application, necessitating alternative geroprotective interventions. Here we develop an interpretable transcriptomic age predictor in human fibroblasts and perform a cDNA overexpression screen to identify factors that...

Population aging has accelerated globally, making successful aging a key public health priority. Zhuang and Gao address the prospective association between cumulative average grip strength and successful aging using three international cohorts. While their multi-cohort design offers valuable cross-population insights, several methodological choices warrant consideration. Grip strength may not fully capture functional determinants of successful aging. Self-reported chronic disease introduces...

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Attention deficit-hyperactivity disorder (ADHD) is a medical condition that is present in approximately 2.5% of adults worldwide and manifests in a variety of different ways across the lifespan. Adults with ADHD often have coexisting psychiatric disorders such as anxiety, mood, sleep, substance use, and personality disorders and are at increased risk for coexisting somatic conditions such as obesity, cardiovascular and cerebrovascular disease, type 1 and type 2 diabetes, and immune and...

Senescent cells develop a persistent inflammatory signature with broad consequences for tissue function and disease. Martini et al.¹ show that mitochondrial citrate metabolism drives inflammation through a pathway that acts independently of mitochondrial DNA-driven immune signaling yet cooperates with it to amplify the inflammatory response.