Aging & Longevity

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)...

Astrocytes are crucial to brain homeostasis, yet their changes along the spatiotemporal progression of Alzheimer's disease (AD) neuropathology remain unexplored. Here we performed single-nucleus RNA sequencing of 628,943 astrocytes from five brain regions representing the stereotypical progression of AD pathology across 32 donors spanning the entire normal aging to severe AD continuum. We mapped out several unique astrocyte subclusters that exhibited varying responses to neuropathology across...

The vasculature of the skeletal system is crucial for bone formation, homoeostasis and fracture repair, yet the diversity and specialization of bone-associated vessels remain poorly understood. Here we identify a specialized type of post-arterial capillary, termed type R, involved in bone remodelling. Type R capillaries emerge during adolescence around trabecular bone, possess a distinct morphology and molecular profile, and are associated with osteoprogenitors and bone-resorbing osteoclasts....

CONCLUSIONS: Hearing impairment can be a modifiable risk factor for AD, and thus its treatment in the aging population is important. Although we did not observe an association between visual impairment and AD, all sensory impairments decrease functioning and quality of life among older adults. Therefore, they should be treated, also among persons with cognitive decline or cognitive disorder.

While racial inequities in dementia risk are well-documented in the United States, research has paid less attention to role of US Southern context in shaping dementia risk through life course exposures. In this study, we examine how Southern birth and Southern residence in adulthood are linked to dementia incidence for Black and White older adults in the United States. Using the Health and Retirement Study (N = 15,613), we estimate a series of hazard models to evaluate how life course risk...

BACKGROUND: The Human Development Index (HDI)-a composite metric encompassing a population's life expectancy, education, and income-is used widely for assessing and comparing human development and wellbeing at the country level, but does not account for within-country inequality. In this study of the USA, we aimed to adapt the HDI framework to measure the HDI at an individual level to examine disparities in the distribution of wellbeing by race and ethnicity, sex, age, and geographical location.

We employed an untargeted proteo-metabolomic approach to profile circulating biomarkers in plasma samples from the I-Lan Longitudinal Aging Study, aiming to identify biomarkers and pathways associated with physio-cognitive decline syndrome (PCDS). In 115 propensity score-matched PCDS case-control pairs, pathway analyses implicated dysregulation of fatty acid metabolism and inflammation in PCDS pathogenesis. Sex-specific associations were observed, with disruptions in central carbon metabolism...

The "Stress Tests and Biomarkers of Resilience" conference, hosted by the American Geriatrics Society and the National Institute on Aging, marks the second in a series aimed at advancing the field of resilience science. Held on March 4-5, 2024, in Bethesda, Maryland, this conference built upon the foundational work from the first conference, which focused on defining resilience across various domains-physical, cognitive, and psychosocial. This year's gathering centered around three factors: the...