Aging & Longevity

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CONCLUSION: Integrating multimodal neuroimaging with ML enhances diagnostic accuracy for AD and MCI and identifies potential neuroimaging biomarkers, providing objective evidence to support early clinical intervention.

ObjectivesObesity is common among older Black adults, but its underlying drivers, such as neighborhood racial composition (NRC), remain understudied. This study examined the association between NRC and obesity among older Black adults, evaluating the role of individual-level socioeconomic status (SES).MethodsData from the Nashville Stress and Health Study was linked to five-year estimates from the American Community Survey. Obesity was defined as body mass index ≥30 kg/m². NRC was measured with...

Chronological age predicts cancer survival but does not capture differences in biological aging rates. We apply FaceAge, an artificial intelligence algorithm that predicts biological age from a facial photograph, to serial clinical facial photographs to calculate the Face Aging Rate (FAR; change in FaceAge divided by the time between photographs). We analyze data from 2276 cancer patients receiving radiation therapy, using photographs captured during routine care. Higher FAR is associated with...

Reproductive aging is an increasing health concern that affects family planning and overall well-being. While extensively studied in females, the mechanisms driving male reproductive aging remain largely unexamined. Here, we found that mammalian Sirtuin 7 sustains spermatogenesis in an age-dependent manner. Sirtuin 7 deficiency in mice increases histone H3 lysine 36 acetylation in spermatogonia and spermatocytes, a pattern also observed during natural aging, and leads to altered chromatin...

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Musculoskeletal pain and mobility disability are common in older adults, but relationships among pain parameters and physical performance are poorly understood. We quantified the impact of different pain measures-recalled and movement-evoked pain-on walk and stair climb time in older adults from the Study of Muscle, Mobility and Aging (SOMMA). In SOMMA (N = 879, age = 76.3 ± 5.0 years, 59% women, 84% non-Hispanic White), participants completed usual pace 400-m walk (avg = 6.6 ± 1.2 min) and...

Ageing-related diseases (ARDs) display diverse phenotypes yet share an age-dependent rise in incidence, suggesting mechanistic links with ageing processes. We examined whether ageing-related genes differ systematically from genes associated with multiple ARD clusters. Across 57 ARDs from UK Biobank, network analyses showed that ageing-related genes, although rarely ARD-associated, lie significantly closer to many ARDs through greater-than-chance proximity in protein-protein interaction (PPI) and...

T cell immunosenescence refers to the progressive functional decline of T lymphocytes with aging, characterized by the phenotypic markers, mitochondrial dysfunction, and the senescence-associated secretory phenotype (SASP), representing a pivotal aspect of overall immune aging. This review systematically elucidates the critical role of T cell immunosenescence in the pathogenesis of common inflammatory skin diseases, including psoriasis, atopic dermatitis, rosacea, and seborrheic dermatitis....

Sirtuin 1 (SIRT1) was initially identified as an enzyme that deacetylates histones and suppresses gene activity. Since then, its roles have expanded considerably, and it is now recognized as a multifunctional protein conserved across various organisms. Despite increasing interest, it remains essential to clarify how exercise-induced changes in SIRT1 counteract multiple hallmarks of aging, as well as the full scope of SIRT1's impact on different physiological systems. This review highlights...

Stress response pathways are emerging as conserved modulators of lifespan. The prevailing hypothesis is that activation of stress-responsive pathways, including the amino acid deprivation arm of the integrated stress response (ISR; the GCN2-ATF4 pathway), is prolongevity. Activation of ATF4 orthologs extends lifespan in Saccharomyces cerevisiae and Caenorhabditis elegans, but its role in other longer-lived organisms remains unclear. We comprehensively tested the role of the GCN2-ATF4 pathway in...

Chronic neural interfaces are essential for advancing brain-computer interfaces, neuroprosthetics, and neuromodulation technologies. However, a long-standing trade-off between performance and longevity persists due to the scarcity of materials that simultaneously achieve superior electrical performance, mechanical compliance, and biocompatibility. Here, we overcome this limitation with an all-organic, ultraflexible electrocorticography (ECoG) design that features a thickness of only 9 µm,...

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Age-associated changes in organelle structure are often viewed as passive deterioration. Our recent work challenges this view by identifying an evolutionarily conserved, age-onset remodeling of the endoplasmic reticulum (ER) that is actively driven by ER-phagy. Across multiple cell types and organisms, the ER undergoes a reduction in volume and a shift from rough ER sheets to tubular networks. ER compositional shifts accompany these changes in morphology, with declines of the proteostasis...

Alzheimer's disease (AD) is a progressive neurodegenerative disorder traditionally defined by amyloid-β plaques and tau tangles. However, growing evidence indicates that deeper disruptions in cellular homeostasis contribute to disease onset and progression. Among these, impaired communication between mitochondria and the nucleus has emerged as a central yet underrecognized pathological feature. Mitochondrial-nuclear (mito-nuclear) crosstalk regulates energy metabolism, stress responses, and...

Sarcopenia is an age-related condition characterized by loss of skeletal muscle mass and strength and is associated with increased cancer incidence and mortality, yet how muscle decline promotes tumorigenesis remains unclear. Here, we show that skeletal muscle functions as an anti-tumor organ by secreting extracellular vesicles (EVs) that suppress tumor growth. Using Drosophila melanogaster and mouse cancer models, we demonstrate that muscle-derived EVs inhibit tumorigenesis. In contrast,...

Amyloid assembly in vivo occurs in complex environments where multiple aggregation-prone species coexist. Aβ and medin are prevalent amyloids in ageing humans that co-localize in cerebral amyloid angiopathy (CAA), yet their structural interactions remain poorly understood. Here, using cryo-electron microscopy, we determine high-resolution fibril structures from in vitro mixtures of Aβ40 and medin. From the same reaction, we resolve three distinct fibril populations: (i) a previously...

Aging is driven in part by progressive deterioration of proteostasis and antioxidant defense, leading to cellular dysfunction and age-associated disease. The naturally occurring methylated inositol D-pinitol (DP) was reported to present metabolic, antioxidant, and anti-inflammatory effects, as well as to extend the lifespan of D. melanogaster and C. elegans through the insulin/IGF-1 signaling pathway. But the mechanism of DP on delay aging remains poorly understand. Here, we showed that 200 μM...

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Retinal ganglion cell (RGC) axons form the optic nerve (ON). Numerous age-related ON diseases, including glaucoma, the second most common cause of worldwide blindness, result from multiple RGC stressors. Nearly all ON astrocytes in the optic nerve head (ONH): the junctional region between the ON and the retina in young-adult rodents expresses the homeodomain only (Hopx) protein. Hopx(+) ONH astrocytes are depleted during aging. ONH primary cultures which include Hopx(+) astrocytes secrete...