Aging & Longevity

During myogenic differentiation, the cellular architecture and proteome of muscle stem cells and myoblasts undergo extensive remodeling. These processes are partially understood and display alterations in disease and aging, resulting in impaired regeneration. Here, we used mass spectrometry to quantify the temporal dynamics of over 6000 proteins during myogenic differentiation. We identified the actin nucleator leiomodin 1 (LMOD1) among a restricted subset of cytoskeletal proteins increasing in...

Intrinsic capacity (IC) reflects multidomain functional reserve and a measurable phenotype of healthy ageing, but its biological correlates remain incompletely understood. We examined associations of neurofilament light chain (NfL), CXCL9 and inflammatory biomarkers with IC in community-dwelling older adults. We conducted a cross-sectional analysis within the Screening and Prevention of Intrinsic Capacity Decline in Elders (SPICE) programme. IC was derived from locomotion (SPPB), cognition...

Brain MRI shows promise for predicting cognitive functioning, but its utility depends on its capacity to capture stable between-person differences (e.g., patient stratification), longitudinal within-person changes (e.g., prognosis, treatment monitoring), or both. Using longitudinal data from 450 adults (aged 21-90; up to three waves, five years apart) in the Dallas Lifespan Brain Study, we benchmarked five modalities, task fMRI, functional connectivity (FC), structural MRI (sMRI),...

Much focus has shifted towards understanding how glial dysfunction contributes to age-related neurodegeneration due to the critical roles glial cells play in maintaining brain health. Cell-cell interactions, which are largely mediated by cell-surface proteins, control many critical aspects of development and physiology; as such, dysregulation of glial cell-surface proteins is hypothesized to play an important role in age-related neurodegeneration. However, it remains technically difficult to...

Epigenetic aging clocks based on DNA methylation patterns across the genome have emerged as a potential biomarker for risk of age-related diseases, like Alzheimer's disease (AD), and environmental and social stressors. However, methylation clocks have not been comprehensively validated in genetically diverse individuals. Here, we evaluate a set of first-, second-, and third-generation methylation clocks in 621 AD patients and matched controls from African American, Hispanic, and White cohorts....

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Cerebral hemodynamic dysfunction is a key driver of unhealthy brain aging. Impaired microcirculatory reactivity leads to uneven perfusion, rendering deeper brain regions more vulnerable and thereby contributing to cognitive decline. Yet how capillaries contribute to these deficits remains poorly defined. Here we combined spatial transcriptomics with in vivo two-photon and three-photon imaging to measure layer-specific cerebral blood flow in control and small vessel disease model mice (CADASIL...

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CONCLUSIONS: FIB-4 appears to reflect reduced biological reserve and systemic vulnerability rather than isolated liver dysfunction. As a cost-free parameter derived from routine blood tests, FIB-4 may represent a practical tool for risk stratification in hospitalized frail older adults.

BACKGROUND: Subjective cognitive decline (SCD) is a preclinical condition associated with an increased risk of dementia and Alzheimer's disease, with no consensus regarding effective therapeutic interventions to date. As the global burden of aging-related neurodegenerative diseases continues to rise, early intervention has become increasingly critical. Cognitive training has been proposed as a promising behavioral intervention; however, few studies have integrated multimodal assessments to...

Consistent with humans and other metazoans, the nematode Caenorhabditis elegans (C. elegans) undergoes progressive structural and functional decline during aging. Possessing highly conserved genetic pathways that share extensive homology with human genes, and characterized by a streamlined, fully mapped connectome, C. elegans has emerged as a robust model for dissecting the mechanisms underlying neuronal aging and degeneration. In this review, we summarize the intrinsic advantages of C. elegans...

[This corrects the article DOI: 10.3389/fnagi.2026.1833368.].

Vascular dysfunction in aging is driven by multiple interconnected hallmarks of aging, including DNA damage, oxidative stress, chronic inflammation, mitochondrial dysfunction, and cellular senescence and features by endothelial impairment, inflammation, and reduced nitric oxide-cyclic guanosine monophosphate (NO-cGMP) signaling. Targeting this pathway may offer therapeutic benefit beyond traditional atherosclerosis-focused treatments. A systematic review and meta-analysis were conducted...

Declining spatial navigation abilities are a critical hallmark of aging, where the loss of spatial abilities precedes global cognitive impairment. While navigational decline is traditionally attributed to deficits in higher-order cognitive functions, emerging cognitive-motor frameworks suggest that age-related sensorimotor alterations play a significant, yet previously overlooked, role. Here, we investigate the coupling between locomotor integrity and navigation by combining an immersive...

Cytotoxic chemotherapy is intended to eliminate transformed cells but can also provoke therapy-induced senescence, a persistent and pro-inflammatory cell state that can promote tumor progression. The molecular mechanisms that govern the apoptosis-senescence fate decision remain incompletely understood. Here, we show that the mitochondrial pore-forming proteins BAX and BAK function as a critical checkpoint that restricts entry to therapy-induced senescence. Genetic ablation of BAX and BAK...

Aging is a fundamental driver of cardiovascular and cerebrovascular comorbidities, yet the mechanisms linking aging to concurrent heart and brain diseases remain incompletely understood. The neurovascular interface (NVI) refers to the structural and functional interface through which neural, vascular, and extracellular-matrix signals interact. In the CNS, this concept substantially overlaps with the classical neurovascular unit, whereas in the heart it refers to an emerging heart tissue-specific...

The ageing process is often portrayed as a steady linear decline, as reflected by the methodological frameworks used to study it. Although linear models successfully capture relevant age-related mechanisms, they may fail to identify key transition states occurring during the lifespan. Indeed, ageing entails a series of transitions - from early development, through adolescence, to older age - that are each characterized by distinct biological remodelling events. The study of these underlying...

Brain aging, the strongest risk factor for Alzheimer's disease (AD), varies across cortical regions. Global brain age (GBA), an imaging-derived measure of neuroanatomic decline, reduces structural aging to a single summary value. This can potentially obscure regional patterns of cognitive vulnerability preceding AD. This study introduces a deep-learning architecture trained on the [Formula: see text]-weighted MRIs of 14,748 cognitively normal (CN) participants from multiple sites to estimate...

Endothelial cells are critical in the regulation of blood pressure. We previously demonstrated AGGF1 was crucial for maintaining endothelial cell function. This study aims to examine whether AGGF1 regulates blood pressure. Here, we found that AGGF1 expression was inversely correlated with blood pressure with age. In male mice, endothelial-specific loss of function of Aggf1 (Aggf1^(flox/flox)/Tie2-Cre^(+)) significantly increased blood pressure, whereas endothelial-specific human AGGF1...

CONCLUSIONS: We were unable to detect a significant association between a hip fracture and new onset of cognitive impairment in older adults. However, conclusions are limited by large confidence intervals. There was a signal toward a positive association, particularly for probable dementia. Future research should be performed in larger sample sizes with rigorous matching to understand risk factors for developing cognitive impairment after hip fracture.