Aging & Longevity

Age-related alterations in the immune system are starting to emerge as key contributors to impairments found in aged organs. A decline in regenerative capacity is a hallmark of tissue aging; however, the contribution of immune aging to regenerative failure is just starting to be explored. Here, we apply a strategy combining single-cell RNA sequencing with flow cytometry, histological analysis, and functional assays to perform a complete analysis of the immune environment of the aged regenerating...

The cognitive reserve (CR) hypothesis posits that individuals can differ in how their brain function is disrupted by pathology associated with aging and neurodegeneration. Here, we test this hypothesis in the continuum from cognitively normal to at-risk stages for Alzheimer's Disease (AD) to AD dementia using longitudinal data from 490 participants of the DELCODE multicentric observational study. Brain function is measured using task fMRI of visual memory encoding. Using a multivariate...

Decline in mitochondrial function is linked to decreased muscle mass and strength in conditions like sarcopenia and type 2 diabetes. Despite therapeutic opportunities, there is limited and equivocal data regarding molecular cues controlling muscle mitochondrial plasticity. Here we uncovered that the mitochondrial mRNA-stabilizing protein SLIRP, in complex with LRPPRC, is a PGC-1α target that regulates mitochondrial structure, respiration, and mtDNA-encoded-mRNA pools in skeletal muscle. Exercise...

The genetic architecture of white matter lesions (WMLs) in Asian populations has not been well-characterized. Here, we performed a genome-wide association study (GWAS) to identify loci associated with the WML volume. Brain MRI and DNA samples were collected from 9479 participants in the Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD). The GWAS confirmed three known WML-associated loci (SH3PXD2A, GFAP, and TRIM47). The lead variant of GFAP was a common missense variant...

Cellular senescence is not only associated with ageing but also impacts physiological and pathological processes, such as embryonic development and wound healing. Factors secreted by senescent cells affect their microenvironment and can induce spreading of senescence locally. Acute severe liver disease is associated with hepatocyte senescence and frequently progresses to multi-organ failure. Why the latter occurs is poorly understood. Here we demonstrate senescence development in extrahepatic...

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Age-related hearing loss (ARHL) is a common disease among the elderly. Although its pathogenesis remains unclear by now, it is widely accepted that ARHL is associated with the degenerative alterations within each component of the cochlea. Extracellular matrix (ECM) plays a crucial role in cochlear structure and function, providing not only structural support but also participating in vital physiological processes including the development, differentiation, survival of auditory sensory cells, and...

The bone marrow microenvironment is a critical regulator of haematopoietic stem cell self-renewal and fate¹. Although it is appreciated that ageing, chronic inflammation and other insults compromise bone marrow function and thereby negatively affect haematopoiesis², it is not known whether different bone compartments exhibit distinct microenvironmental properties and functional resilience. Here we use imaging, pharmacological approaches and mouse genetics to uncover specialized properties of...

Motor skill repertoire can be stably retained over long periods, but the neural mechanism that underlies stable memory storage remains poorly understood^(1-8). Moreover, it is unknown how existing motor memories are maintained as new motor skills are continuously acquired. Here we tracked neural representation of learned actions throughout a significant portion of the lifespan of a mouse and show that learned actions are stably retained in combination with context, which protects existing...

While senescent cells have detrimental roles in several contexts, they are highly heterogeneous. p16 highly expressing senescent cells have been reported to exert beneficial functions in wound healing. Here we use Xenium spatial transcriptomics to identify a distinct p21 highly expressing senescent population induced on wounding, with a pro-inflammatory profile. We find that clearing p21 highly expressing cells expedites wound closure and is partially mediated by NF-κB inhibition, thus enhancing...

The availability of proteomics data in large, population-based cohort studies offers an unprecedented opportunity to understand the onset and progression of aging-related diseases and syndromes. We examined the proteomic signature of the onset of frailty and the progression to death among the prefrail and frail. A total of 2920 proteins were assayed using Olink among 43,895 participants (aged 39-70 years) in the UK Biobank. Using multinomial logistic models, we identified 102 and 90 proteins...

Several mouse lines with congenital growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis disruption have shown improved health and extended lifespan. The current study investigated how inactivating this axis, specifically during aging, impacts the healthspan. We used a tamoxifen-inducible global GH receptor (GHR) knockout mouse model starting at 12 months and followed the mice until 24 months of age (iGHRKO(12-24) mice). We found sex- and tissue-specific effects, with some being...

Programmed cell death occurring during plant development (dPCD) is a fundamental process integral for plant growth and reproduction. Here, we investigate the connection between developmentally controlled PCD and fungal accommodation in Arabidopsis thaliana roots, focusing on the root cap-specific transcription factor ANAC033/SOMBRERO (SMB) and the senescence-associated nuclease BFN1. Mutations of both dPCD regulators increase colonization by the beneficial fungus Serendipita indica, primarily in...

CONCLUSION: The methodological and reporting quality of multimorbidity guidelines were suboptimal. The recommendations of these guidelines covered primarily the management process of multimorbid patients. Future guidelines should pay more attention to the scientific quality of the development methodology and the feasibility of implementing the guidelines in practice.

Investigating brain-enriched proteins with machine learning methods may enable a brain-specific understanding of brain aging and provide insights into the molecular mechanisms and pathological pathways of dementia. The study aims to analyze associations of brain-specific plasma proteomic aging signature with risks of incident dementia. In 45,429 dementia-free UK Biobank participants at baseline, we generated a brain-specific biological age using 63 brain-enriched plasma proteins with machine...

Increased activity of the heat shock factor, HSF-1, suppresses proteotoxicity and enhances longevity. However, the precise mechanisms by which HSF-1 promotes lifespan are unclear. Using an RNAi screen, we identify ubiquilin-1 (ubql-1) as an essential mediator of lifespan extension in worms overexpressing hsf-1. We find that hsf-1 overexpression leads to transcriptional downregulation of all components of the CDC-48-UFD-1-NPL-4 complex, which is central to both endoplasmic reticulum and...

CONCLUSION: This study found that LLD patients with severe depression-anxiety, low activation, normal cognitive function, involuntary admission, and strong objective support exhibited a high level of suicide risk. These patients should receive intensified monitoring and comprehensive measures should be implemented to prevent the occurrence of suicidal behaviors during hospitalization.

In modern human societies, social interactions and pro-social behaviours are associated with better individual and collective health, reduced mortality, and increased longevity. Conversely, social isolation is a predictor of shorter lifespan. The biological processes through which sociality affects the ageing process, as well as healthspan and lifespan, are still poorly understood. Unveiling the physiological, neurological, genomic, epigenomic, and evolutionary mechanisms underlying the...

Introduction The problem of population aging is intensifying worldwide. Osteoporosis has become an important cause affecting the health status of older populations. However, the diagnosis of osteoporosis and people's understanding of it are seriously insufficient. We aim to develop a deep learning model to automatically measure bone mineral density (BMD) and improve the diagnostic rate of osteoporosis. Methods The images of 801 subjects with 2080 vertebral bodies who underwent abdominal paired...

Life stress can shorten lifespan and increase risk for aging-related diseases, but the biology underlying this phenomenon remains unclear. Here we assessed the effect of chronic stress on cellular senescence-a hallmark of aging. Exposure to restraint stress, a psychological non-social stress model, increased p21^(Cip1) exclusively in the brains of male, but not female mice, and in a p16^(Ink4a)-independent manner. Conversely, exposure to chronic subordination stress (only males were tested)...