Aging & Longevity

Hematopoietic stem cells integrate local and systemic cues to sustain blood homeostasis. In this issue of Cell Stem Cell, Tian et al.¹ uncover a stress-responsive brain-gut-bone marrow axis that drives aging-like dysfunction of hematopoietic stem cells.

Chronic stress influences hematopoietic stem cells (HSCs). However, how psychological stress regulates HSC function remains incompletely understood. Here, we show that psychological stress impairs HSC self-renewal and lymphoid differentiation, inducing aging-like phenotypes. Stress suppresses neuronal activity in the medial prefrontal cortex (mPFC) and periaqueductal gray (PAG), leading to HSC dysfunction, whereas chemogenetic activation of these regions restores HSC function. Psychological...

Atherosclerosis imposes a heavy burden on global healthcare systems and remains the leading cause of mortality worldwide, with macrophage dysfunction playing a critical role in its pathogenesis. This review examines the dual roles of macrophage senescence and programmed cell death (PCD) in the progression of atherosclerosis, highlighting their mechanisms, cross-talk and emerging therapeutic strategies. Macrophage senescence-characterized by irreversible cell cycle arrest, mitochondrial...

Oceanic trench bending over 1000 km occurs globally, with notable along-trench variations in mantle wedge thermochemistry. However, the mechanisms influencing both shallow trench geometry and deep mantle state remain unclear. Here we focus on the Mariana Trench as a representative case. Our 3D model successfully replicates its curved geometry. Modeling results further reveal that extensive intra-oceanic trench retreat and bending occur when the incoming plate features sharp density variations...

Perturbations in lysosome integrity are tightly linked to neurological disorders and ageing, but the underlying pathogenic mechanisms are incompletely understood. Using an unbiased proteomic approach, we here identified the bridge-like lipid transport protein VPS13C/PARK23 as a key component of a global early response pathway to lysosome damage. VPS13C readily binds lysosomes under mechanical or osmotic tension in anticipation of membrane lesions. The latter trigger a conformational change in...

Recent studies have highlighted the crucial role of mechanical properties in the ovarian microenvironment for ovarian function. However, the mechanisms that cause ovarian matrix stiffening during aging remain incompletely understood. Here we utilized atomic force microscopy (AFM) to demonstrate that human ovarian matrix stiffness increases with aging and in pathophysiological conditions, such as chemotherapy-induced premature ovarian insufficiency (POI), polycystic ovary syndrome (PCOS) and...

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The d emographic shift toward an older population is accelerating the prevalence of age-related diseases. Precision geromedicine represents a paradigm shift in targeting the biological processes of ageing to optimise health and healthspan, which likely requires multimodal tailored interventions. PROMETHEUS, as part of the XPRIZE healthspan semi-finalist competition, is an 8-week feasibility and exploratory study including 20 middle-aged-to-older participants who received a multimodal...

[This corrects the article DOI: 10.1371/journal.pbio.3003306.].

Despite well-documented poor health outcomes among homebound older adults with diabetes, little is known about how homebound status affects glycemic outcomes. This study examined the association between homebound status and glycemic control among community-dwelling older adults with diabetes and identified key factors associated with glycemic outcomes. We conducted a cross-sectional analysis using data from the 2017 National Health and Aging Trends Survey (NHATS). Participants included...

Wound healing (WH) is a multi-component and highly orchestrated process, in which fibroblasts play a pivotal role. Wound healing is commonly attenuated during aging and the course of cellular senescence (CS). A growing body of evidence demonstrates that mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) can mitigate the aging and CS phenotype. In this study, we evaluated the effects of EVs derived from naïve MSCs (nMSCs) or anti-inflammatory polarized MSCs (pMSCs) on the rate of in...

CONCLUSIONS: No differences in late mortality, SMNs, and most CHCs were observed between patients who received VDC versus VDC/IE. Aging EWS survivors' elevated risk of morbidity and mortality underscores the need for lifelong survivorship care and therapies that reduce the risk for late effects.

CONCLUSIONS: Depressive symptoms appear to be the dominant negative correlate of spiritual well-being in geriatric outpatients, while religious coping shows an independent positive link. The attenuation of functional measures after accounting for depressive symptoms may align with gerotranscendence theory or simply reflect ceiling effects in this functionally well-preserved outpatient sample. Either way, these data underscore the relevance of addressing depressive symptoms and acknowledging...

CONCLUSION: Higher social participation is strongly associated with better subjective well-being in older adults, particularly through relational and health-oriented activities. Social participation scores may serve as a useful community-based indicator for detecting low well-being. Culturally sensitive interventions that promote meaningful, voluntary, and inclusive participation-alongside structural supports such as transportation and social prescribing-may help enhance psychological well-being...

CONCLUSIONS: CHAMPS, PASE, and LAPAQ showed the most acceptable psychometric properties. Most PROMs had limited responsiveness and inconsistencies. Implementation should focus on robust PROMs, while research should enhance measurement quality, validate tools in home care settings, and standardize measurement methods.

CONCLUSIONS: Medical students mostly demonstrated positive attitudes towards older people, particularly in terms of respect and willingness to provide support. Regular contact with older people and appropriately designed gerontological education may contribute to more positive attitudes towards older adults and help counteract ageism among future healthcare professionals.

Senescence of immune cells can drive senescence of solid organs, and reversing immune cell senescence ameliorates organismal senescence phenotypes. As the second largest subset of decidual immune cells, macrophages play a critical role in pregnancy. However, whether decidual macrophages (DM) exhibit senescence in advanced maternal age (AMA) pregnancies (≥ 35 years old) and their involvement in AMA-related adverse outcomes remain undefined. This study elucidates the phenotypic and functional...

Age-related breakdown of the blood-brain barrier (BBB) is associated with cerebrovascular and neurodegenerative diseases, yet its underlying mechanisms remain unclear. Here, we find that BBB leakage begins in midlife and is driven primarily by increased endothelial caveolar transcytosis rather than tight junction disruption. AAV-mediated knockdown of caveolin-1 or restoration of Mfsd2a expression reduces endothelial vesicle formation and BBB leakage in aged mice. Transforming growth factor...

Conventional BMI-based classifications, even when combined with traditional cardiometabolic risk factors, limit precision in aging-related risk assessment. Here, we perform metabolomic analysis in 13,202 older adults from the natural aging cohort (NCT04517513). Leveraging a panel of 39 core metabolites, we develop accurate and interpretable machine learning models to identify metabolic dysfunction across different BMI categories, achieving area under the receiver operating characteristic curve...