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Previous reports revealed immune dysfunction, chromosomal abnormalities, cytokine deregulation, and telomere alterations after prolonged spaceflight. However, the stress of space on hematopoietic stem and progenitor cells (HSPCs) and the resilience properties maintaining lifelong hematopoiesis and immunity were not studied. We performed HSPC functionally organized multi-omics aging and resilience (HSPC-FOMA-R) analyses in 9 astronauts before, during, and after three short-duration International...

Translation is made of initiation, elongation, and termination. The role of termination in relaying extracellular outputs to the translation machinery is unknown. We show, in mice, that the controlled recycling of ribosomes post-termination is a major checkpoint that integrates mitogenic signals and antiviral responses. In detail, the recycling of ribosomes at stop codons, maximal translation, and cellular proliferation strictly depend on eIF6 phosphorylation, both in vitro and in vivo. Lack of...

Structural topology develops non-linearly across the lifespan and is strongly related to cognitive trajectories. We gathered diffusion imaging from datasets with a collective age range of zero to 90 years old (N = 4,216). We analyzed how 12 graph theory metrics of organization change with age and projected these data into manifold spaces using Uniform Manifold Projection and Approximation. With these manifolds, we identified four major topological turning points across the lifespan - around...

We investigate the effects of α-Klotho, an anti-aging hormone, on cell proliferation across three tissues with varying regenerative capacities in the context of aging. Using young and old wild-type mice, alongside old heterozygous Klotho-deficient mice, we administered soluble α-Klotho (sKL) daily for 10 weeks to elucidate the impact of α-Klotho deficiency and its supplementation. Our investigation spanned three organs: the small intestine, the kidney, and the heart. We measured cell cycle...

Senescence-associated frailty and sarcopenia are global challenges. We here investigated neuronal activity and skeletal muscle biology in senescence-accelerated mouse prone 8 (SAMP8) mice with scalp acupuncture stimulation (SAPS). Excise activity was assessed using rotarod test in the three groups: SAMP8 mice receiving SAPS (SP8-Ap), SAMP8 controls (SP8-C), and senescence-accelerated mouse resistant 1 controls (SR1). SP8-Ap exhibited significantly improved exercise activity compared to SP8-C....

Aneuploid cells are known to increase with age. Previously, we demonstrated an increased number of aneuploid fibroblasts isolated from aged mice due to chromosomal instability (CIN), which is caused by oxidative stress. It is unclear whether this phenomenon also occurs in human cells, which are more resistant to oxidative stress than mouse cells. Here, we found that fibroblasts from aged individuals exhibited an increase in aneuploid cells. The frequency of chromosome missegregation and...

No abstract

Intestinal stem cells (ISCs) drive the rapid regeneration of the gut epithelium. However, during aging, their regenerative capacity wanes, possibly through senescence and chronic inflammation, albeit little is known about how aging-associated dysfunction arises in the intestine. We previously identified the urokinase plasminogen activator receptor (uPAR) as a senescence-associated protein and developed CAR T cells able to efficiently target it. Harnessing them, here, we identify the accumulation...

Aging exacerbates organ injury in endotoxemia, but it is not clear whether endotoxemia is associated with a specific, age-related profile of the endothelial response. Therefore, the aim of the study was to assess the pattern of endothelial response to lipopolysaccharide (LPS) in aged mice (18-month-old) as compared to young mice (3-month-old). Our analysis was based on functional endothelial responses measured in vivo by magnetic resonance imaging (MRI) and on a comprehensive panel of biomarkers...

Arterial aging is associated with enhanced angiotensin II (Ang II) signaling via Ang II type 1 receptor (AT1R) and with microRNA-34a (miR-34a) increased expression. AT1R-associated protein (ATRAP/Agtrap) binds to AT1R, promotes its internalization, and inhibits Ang II signaling. This study addresses the hypothesis that miR-34a targets ATRAP/Agtrap and enhances Ang II pro-inflammatory signaling via AT1R in arterial vascular smooth muscle cells (VSMC). Our results show that miR-34a exhibits an...

Protein misfolding plays a central role in diseases such as Alzheimer's disease, Parkinson's disease, type 2 diabetes, and transthyretin amyloidosis (ATTR), often driven by specific aggregation-prone segments such as Aβ(17-23) and Aβ(37-42) of amyloid-β42 (Aβ42), α-Syn(66-74) and α-Syn(71-82) of α-synuclein (α-syn), hIAPP(22-27) of human islet amyloid polypeptide (hIAPP), and TTR(105-115) of transthyretin (TTR). Capturing the atomic-level structural features of these transient and dynamically...

CONCLUSION: Differences in state-level health system capacity may disproportionately affect socioeconomically disadvantaged populations, underscoring the need for more equitable hypertension management and cardiovascular health strategies across India.

CONCLUSIONS: Relationships between joint pain and poor sleep quality among older adults with radiographic knee OA were similar, regardless of physical activity level. Our results highlight the high prevalence of both sleep disturbance and significant knee pain in this group, illustrating the need to consider supportive measures as appropriate in this population.

With the aging population in Europe, particularly Hungary, unhealthy aging is emerging as a growing public health challenge. Physical inactivity is a modifiable risk factor for age-related diseases and remains highly prevalent. Increasing daily physical activity is a key strategy for extending health span. Step-count-based interventions, including motivational interviewing and email-based feedback, have been shown to promote physical activity, but direct comparisons of these approaches in...

Controversies over anti-amyloid immunotherapies underscore the need to elucidate their mechanisms of action. Here we demonstrate that Lecanemab, a leading anti-β-amyloid (Aβ) antibody, mediates amyloid clearance by activating microglial effector functions. Using a human microglia xenograft mouse model, we show that Lecanemab significantly reduces Aβ pathology and associated neuritic damage, while neither fragment crystallizable (Fc)-silenced Lecanemab nor microglia deficiency elicits this effect...

Alzheimer's disease causes progressive cognitive decline, yet some individuals remain resilient despite developing hallmark pathology. A subset of people with Down syndrome (DS), the most common genetic cause of Alzheimer's disease, demonstrates such resilience. Given the elevated risk of hematopoietic mutations in DS, we hypothesize that certain variants may confer microglial resilience. Here, we introduce a myeloid DS-linked CSF2RB A455D mutation into human pluripotent stem cell-derived...

Delirium is an acute change in cognition, common in hospitalized older adults, and associated with high healthcare and human cost; however, delirium's genetic and proteomic background remains poorly understood. Here we conducted a genetic meta-analysis on delirium using multi-ancestry data from the UK Biobank, FinnGen, All of Us Research Program and Michigan Genomics Initiative cohorts (n = 1,059,130; 11,931 cases), yielding the Apolipoprotein E (APOE) gene as a strong delirium risk factor...

No abstract

Ageing dampens the regenerative potential of intestinal epithelium across species including humans, yet the underlying causes remain elusive. Here we characterized the temporal dynamics of regeneration following injury induced by 5-fluorouracil, a commonly used chemotherapeutic agent, using proteomic and metabolomic profiling of intestinal tissues together with functional assays. The comparison of regeneration dynamics in mice of different ages revealed the emergence of proteostasis stress and...

Alzheimer's disease causes progressive cognitive decline, yet some individuals remain resilient despite developing hallmark pathology. A subset of people with Down syndrome (DS), the most common genetic cause of Alzheimer's disease, demonstrates such resilience. Given the elevated risk of hematopoietic mutations in DS, we hypothesize that certain variants may confer microglial resilience. Here, we introduce a myeloid DS-linked CSF2RB A455D mutation into human pluripotent stem cell-derived...