Aging & Longevity

No abstract

Hematopoietic stem cells (HSCs) transition through different functional states throughout life from emergence and expansion in the fetus, homeostasis maintenance in adulthood, and progressive functional decline with age. Aged HSCs are characterized by increased phenotypic number, decreased self-renewal and long-term reconstitution capacity, myeloid-biased differentiation, and clonal hematopoiesis. In this review, we summarize the life cycle of HSCs, integrate recent advances in understanding the...

Chronic inflammation and aging skew hematopoiesis toward myelopoiesis at the expense of lymphoid output. We screened type 2 and anti-inflammatory cytokines to identify extrinsic signals capable of restoring lymphoid lineage commitment in hematopoietic stem and progenitor cells (HSPCs). Interleukin 4 (IL-4) specifically inhibited inflammation-induced myelopoiesis and shifted multipotent progenitor (MPP) differentiation toward the lymphoid lineage. IL-4 activated a signal transducer and activator...

CONCLUSION: BDNF, FABP-3, OSM and OSTN contributed to a stepwise regression model predicting the FI after adjusting for age, whereas only SPARC remained in a model predicting FP score.

Ageing heterogeneity hampers prevention and care. We used routine biochemical panels and unsupervised learning to identify latent phenotypes in community-dwelling older adults. In 1491 participants from the Toledo Study for Healthy Ageing (TSHA) with ~10-11 years of follow-up, 39 blood biomarkers were dimension-reduced and clustered, yielding three phenotypes: Healthy, Metabolic (subclinical dysmetabolism), and Haematological (low erythroid/renal profile). Phenotypes differed in functional...

Psychotic disorders, including schizophrenia and affective psychosis, affect ~3% of the population and typically emerge in early adulthood. Cardiometabolic disease accounts for much of the 20-year life-expectancy gap in psychosis. Evidence indicates potentially causal processes, often seen in aging, act within and beyond the brain, and before the onset of treatment; these include inflammation, metabolic and mitochondrial dysfunction. Here we synthesize evidence and propose a framework that...

BACKGROUND: Head and neck cancer (HNC) is a common malignant tumor, and its treatment often leads to functional impairments in speech, swallowing, and appearance, severely affecting patients' quality of life. Older individuals with HNC, due to the combined stress of aging and disease, face heightened mental health challenges. This study aims to evaluate the effect of AI-driven personalized health education on mental health, social support and quality of life in older patients after HNC surgery.

CONCLUSIONS: Neutral acceptance may represent a relatively higher-scoring dimension of death attitudes among Chinese older adults. Health-related factors, death-related experiences, and cultural factors appear to be relevant factors associated with death attitudes. Based on these preliminary findings, exploratory interventions, including death education and psychosocial support, could be considered for older adults with poor health. These findings should be interpreted cautiously, given that all...

Aging affects us all, but we still do not know how the process evolves or if we can modulate its pace. This issue of PLOS Biology presents a Collection of articles that explores different aspects of aging, discussing what challenges still need to be overcome.

Intermuscular fat infiltration driven by fibro-adipogenic progenitors contributes to the irreversible progression of sarcopenia and reflects a fate shift associated with altered calcium signaling. Using FAP-based adipogenesis models, structural and biochemical analyses, transcriptomic profiling, and in vivo drug exposure studies, we found that Ca^(2+) influx dyshomeostasis promotes adipogenic commitment by triggering calmodulin remodeling, dissociation of the KCNQ1-CaM-FTO complex, nuclear...

Our post-GWAS functional analysis revealed that cathepsin L (CTSL) is an upstream regulator of CUX1, and it induces p16^(INK4a)-dependent and atherosclerosis-associated senescence by indirectly activating CUX1 transcription in a process that requires its proteolytic activity. This suggests an unidentified transcription regulator between CTSL and CUX1, and CTSL-mediated cleavage of this regulator could transcribe CUX1, inducing senescence. Here, in search of this transcriptional regulator, we...

Aging is a global issue that affects human health and increases disease risk. The traditional concept of the "age gap (AG)," defined as the difference between estimated biological age and an individual's chronological age, has been used for self-monitoring the risk of age-related diseases. However, the current AG does not account for the stratified aging patterns across different stages of chronological age, which may lead to biased or paradoxical interpretations of aging acceleration. To...

CONCLUSION: This study identifies a novel pathological mechanism in age-related MCI: the nuclear accumulation of PANK4 in hippocampal exacerbates cuproptosis susceptibility by specifically impairing ATP7B-dependent copper efflux, leading to copper overload. Astrocyte-specific PANK4 ablation mitigates these effects, highlighting PANK4 as a potential therapeutic target for preventing or treating age-associated cognitive decline.

INTRODUCTION: Parkinson's disease (PD) is characterized by progressive dopaminergic neurodegeneration, neuroinflammation, and emerging evidence of gut microbiota dysbiosis. Although nicotine has been implicated in neuroprotection, whether its enantiomers exert stereoselective effects on the gut-brain axis remains unknown.

Chaperone-mediated autophagy (CMA) is a selective lysosomal pathway essential for proteostasis and stress adaptation that declines with aging and metabolic disease, conditions closely linked to hepatocellular carcinoma (HCC). Using genetically engineered mouse models with systemic, hepatocyte-specific, or T cell-specific deletion of the CMA regulator LAMP2A in an MYC-driven, TP53-deficient HCC context, we demonstrate that CMA exerts cell-type-dependent tumor-suppressive functions....

Speaking more than one language is hypothesized to lead to greater brain resilience in aging and Alzheimer's disease, resulting in a delay in the symptom onset of Alzheimer's disease. While previous research has used structural neuroimaging measures to explore the neural underpinnings of this protective effect, few studies have used functional brain measures. Thus, we used functional connectivity measures of resting-state fMRI data to explore the association between multilingualism and brain...

Aging is characterized by the loss of tissue homeostasis, traditionally captured by the hallmarks of aging, yet how these hallmarks integrate to drive organismal decline remains unresolved. We propose mesenchymal drift, a process in which cells progressively lose lineage identity and adopt mesenchymal features, as a convergent framework that integrates the hallmarks of aging. Accumulating evidence suggests that mesenchymal drift can both arise from and reinforce these hallmarks, forming a...

Glucocorticoids (GCs) are essential endocrine regulators coordinating stress responsiveness, metabolic flexibility, inflammatory resolution, and circadian physiology. While acute GC fluctuations are adaptive, sustained exposure (arising from psychosocial stress, circadian disruption, obesity, chronic inflammation, neoplasms, or steroid therapy) elicits pleiotropic effects that overlap with biological aging. Prolonged GC signaling intersects with multiple hallmarks of aging by altering nutrient...

BACKGROUND: Alzheimer's disease neuropathology, characterised by amyloid β (Aβ) and phosphorylated-tau (p-tau) protein accumulation, has primarily been assessed with biomarkers in clinical samples of older adults. Less is known about plasma biomarkers of Alzheimer's disease neuropathology and their associations with cognitive outcomes in midlife in diverse community-based samples. Our goal was to address these gaps.

BACKGROUND: Tau PET imaging has emerged as a critical biomarker for Alzheimer's disease, informing diagnosis, staging, and therapeutic selection. We investigated whether PET tracer selection alters tau detection.