Aging & Longevity

Cancer cells precisely modulate replication stress to sustain genomic instability without triggering lethal DNA damage, yet regulators enabling this delicate balance remain largely unknown. Here, we identify N-methyl-D-aspartate receptor synaptonuclear signaling and neuronal migration factor (NSMF) as a novel and critical regulator of replication stress in colorectal cancer (CRC). NSMF expression is significantly elevated in CRC tissues and correlates closely with elevated replication stress. In...

Aging is accompanied by profound changes in energy metabolism, yet the underlying drivers and modulators of these shifts remain incompletely understood. Here, we investigated how life-history evolution shapes metabolic aging and pharmacological responsiveness by leveraging Drosophila melanogaster lines divergently selected for reproductive timing. We measured organismal oxygen consumption rate and performed untargeted metabolomics in young and old flies of both sexes from long-lived "O" lines...

Immune cells from the skull marrow reach the meninges through bone channels. In this issue of Immunity, Eme-Scolan and colleagues show that these channels form neonatally and can be remodeled to alter immune access to the brain's borders. Their work suggests that the skull is a developmental checkpoint for neuroimmune defense, potentially shaping vulnerability or resilience across the lifespan.

Dual-task walking, performing a secondary task while walking, challenges attentional and motor resources and has been linked to increased fall risk. While cognitive dual tasks are most often studied, physical (e.g., load carriage) and "combination" tasks such as obstacle crossing may also impact gait. Whole-body angular momentum and its variability provide sensitive markers of locomotor stability. We investigated how dual-task type influences gait mechanics and stability in younger and older...

CONCLUSIONS: These findings highlight PAQR4 as a potential biomarker and a candidate molecule of interest for osteosarcopenia.

Rechargeable zinc metal batteries are promising for large-scale energy storage due to their low cost and high safety, but their development is seriously hindered by the dendritic growth and side reactions of zinc metal anodes. To address this challenge, we report here that rational design of low-surface-tension electrolytes can enable dense nucleation and fine-grained growth of zinc. This low-surface-tension strategy leads to high stability of the solid-electrolyte interface, dendrite-free...

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Senescent cell accumulation contributes to aging, and their clearance represents an effective anti-aging strategy. Current senolytic strategies focus on drug-mediated senescent cell clearance, but it is unknown whether a hypobaric condition can induce senescent cell death. Here we show that hypobaric pressure (HP) at -375 mmHg without hypoxia induces cells to undergo lysosome-dependent cell death (LDCD). Mechanistically, we unveil that HP activates transmembrane protein 59 (TMEM59) to induce...

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Disease tolerance is a defence strategy essential for survival of infections, limiting physiological damage without killing the pathogen^(1,2). The disease course and pathology an infection may cause can change over the lifespan of a host due to the structural and functional physiological changes that accumulate with age. Because successful disease tolerance responses require the host to engage mechanisms that are compatible with the disease course and pathology caused by an infection, we...

Age-related decline in physical function is a hallmark of aging and a major driver of morbidity, disability, and loss of independence in older adults, yet the molecular processes linking muscle aging to functional deterioration remain incompletely defined. Emerging evidence implicates ferroptosis, defined as iron-dependent, lipid peroxidation-driven cell death, as a compelling but underexplored contributor to age-related muscle wasting and weakness. Although ferroptosis signatures appear in aged...

Alzheimer's disease (AD) is characterized by the accumulation of amyloid-β42 (Aβ42) neurotoxic peptides that cause oxidative stress and neurodegeneration. The current study examined the neuroprotective properties of salvianolic acid A (SalA), an antioxidant polyphenol, in a Drosophila melanogaster model of AD. Transgenic flies expressing human Aβ42 were assayed for eye morphology, life span, and locomotor function after SalA diet supplementation. RNA-seq and RT-qPCR were used to quantify...

CONCLUSIONS: In this nationally representative cohort, vision difficulty and motor impairments were independently associated with increased dementia risk over up to 11 years. The presence of multiple sensory difficulties and motor impairments substantially increased the risk of dementia, emphasizing the importance of their early detection and management to reduce dementia risk.

Working memory (WM) processes decline with increasing age. According to recent concepts, it is necessary to differentiate between dynamically changing 'WM states' which are regulated via gating mechanisms. We investigated which neural oscillatory processes underlying WM gating and updating are affected by age with a focus on alpha and theta band activity. With an EEG beamforming approach, we examined the data of N = 132 healthy individuals aged 18-76 years who performed the reference-back...

CONCLUSION: Texture analysis combined with machine learning could provide non-invasive biomarkers to classify muscles of young and old individuals, and assist in function prediction.

CONCLUSIONS AND IMPLICATIONS: Compared with married veterans, widowers had greater rates of cognitive decline, greater difficulty completing IADLs, and increased medical comorbidities. These findings may inform access to mental health services addressing bereavement and other clinical outcomes after widowhood.

Tumor necrosis factor α (TNFα) regulates inflammation in metabolic diseases and probably aging-associated inflammation. Here, TNFα´s role in aging-related liver inflammation and fibrosis and underlying mechanisms was assessed in mice. In male C57BL/6J mice, aging increased hepatic inflammation, senescence markers p16 and p21 and Tnfa mRNA expression in liver tissue. In a second study, 4 and 24-month-old TNFα^(-/-) and wild-type (WT) mice were compared for senescence, liver damage, intestinal...

Age-related inflammation plays a pivotal role in osteoarthritis (OA) pathogenesis, but the mechanism is not fully understood. Here, we identify decreased IL-36 receptor antagonists (IL-36Ra) in epidermal keratinocytes from a premature-aged skin mice model, aged mice and patients. Decreased IL-36Ra leads to increased secretion of IL-36 agonists to serum and joints, which activates proinflammatory signaling and promotes senescence in chondrocytes and synovial fibroblasts, thereby aggravates OA...

CONCLUSION: These findings emphasize the significant geographic disparity in SO prevalence across China and reveal that SO is associated with a substantially elevated risk of dementia, underscoring the need for targeted interventions in aging populations.