Aging & Longevity

CONCLUSIONS: Self-reported gait speed and grip strength measures demonstrated limited validity compared with objective assessments in older adults with mild frailty and should be used cautiously as substitutes for measuring weakness and slowness in this population. Trial Registration: ISRCTN Registry: ISRCTN54268283.

Hutchinson-Gilford progeria syndrome (HGPS) is a rare premature aging disorder most commonly caused by a de novo synonymous mutation (c.1824C>T) in the LMNA gene. This mutation activates aberrant splicing of prelamin A, leading to the production and accumulation of progerin, which drives accelerated aging, with patients predominantly succumbing to cardiovascular disease. However, while cardiac pathologies are well documented, the cell-autonomous contribution of cardiomyocytes to HGPS-associated...

Mitochondria are central regulators of retinal bioenergetics and innate immune signaling, yet how mitochondrial genetic background and aging jointly influence immunometabolic responses in the retina remains poorly defined. Here, we investigated the effects of mitochondrial DNA (mtDNA) variation on retinal function and the combined effects of mtDNA variation and age on bioenergetic composition, mtDNA damage, and the microglial expression and intracellular localization of stimulator of interferon...

To investigate whether CT-derived radiomic features capture imaging patterns associated with chronological age groups in mice and to assess the influence of imaging platform and photon-counting CT reconstruction strategy on classification performance. Female C57BL/6NRj mice from three chronological age groups (28, 88, and 99 weeks; n = 11) underwent clinical photon-counting CT (PCCT) and preclinical Albira II CT. Heart, liver, and spleen were segmented and radiomic features were extracted. The...

Aging is closely associated with dysregulation of lipid metabolism, making the modulation of lipid metabolism a promising strategy for promoting healthspan. Streptococcus thermophilus, a widely utilized probiotic, has shown potential in regulating host metabolism. However, whether and how it can promote healthspan by modulating specific lipid metabolic pathways remains unclear. Using the Caenorhabditis elegans model, this study investigated the effects of Streptococcus thermophilus on healthspan...

Alzheimer's disease (AD) and dementia with Lewy bodies (LBD) are the most widespread forms of degenerative dementia. However, little is known about the molecular aspects that link these conditions with each other and with aging itself. Whole transcriptome analysis and Gene Set Enrichment Analysis (GSEA) have been carried out on brain samples from hippocampus (HI), temporal and parietal cortex (TC, PC), cingulate cortex (CG), and substantia nigra (SN) of subjects with a neuropathological...

Although a loss-of-function variant of TM6SF2 is a highly penetrant risk factor for steatotic liver disease, including progression to cirrhosis and cancer, its normal function is largely unknown. Here we show that endoplasmic reticulum (ER)-localized TM6SF2 forms membrane contact sites (MCSs) with late endosomes/lysosomes, where it activates the small GTPase RAB7 to enable an endolysosomal route for selective secretion of lipid-rich very low-density lipoprotein (VLDL) particles. In accord,...

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...