Aging & Longevity

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...

The C. elegans Argonaute protein PRG-1/Piwi and associated piRNAs protect metazoan genomes by silencing transposons and other types of foreign DNA. As prg-1 mutants are propagated, their fertility deteriorates prior to the onset of a reproductive arrest phenotype that resembles a starvation-induced stress response. We found that late-generation prg-1 mutants with substantially reduced fertility were long-lived, whereas early- or mid-generation prg-1 mutants had normal lifespans. Loss of the...

CONCLUSIONS: The Brief-BESTest test combined with accelerometry could be a suitable screening tool to identify middle-aged people with early balance deterioration and potentially identify those with poor balance and a possible higher risk for falls. Clinicians and policymakers can use our findings to implement balance assessment programs in patients < 65 years, leading to preventive strategies before the risk increases.

CONCLUSION: These findings emphasize the critical role of frailty in the development of CLD, suggesting that targeted interventions could reduce CLD risk.

Cancer is one of the leading causes of death and its prevalence increases with age. While centenarians exhibit extreme longevity and potential to avoid or delay aging-related diseases, their response to cancer is still barely explored. Our study took advantage of the Electronic Health Records to retrospectively compare the severity of cancer in centenarians (n = 649) and non-centenarians (n = 62,753) in the Basque Country (province of Gipuzkoa), Spain, through analyzing all the recorded...

Mapping gut microbial structural variants (SVs) during human aging may provide fundamental knowledge and mechanistic understanding of the gut microbiome's relationship with healthy aging. We characterize gut microbial SVs from 3,230 Chinese participants, identifying key SVs associated with aging, healthy aging, and age-related chronic diseases. Our findings reveal a pattern of copy number loss in aging-related SVs, with 35 core SVs consistently detected. Additionally, eight SVs distinguish...

CONCLUSIONS AND IMPLICATIONS: The overall estimated SA rate among people aged ≥60 years was 22% globally. The SA criteria mainly include 6 aspects: good psychological status, no major diseases, high cognitive function, high physical function, active social engagement, and no disability. Emphasizing the importance of psychological well-being and chronic disease management, the findings offer valuable insights for future research and policy making related to the welfare of aging populations.

Aurora B kinase (AURKB) inhibitors have been trialled in a range of different tumour types but are not approved for any indication. Expression of the human papilloma virus (HPV) oncogenes and loss of retinoblastoma (RB) protein function has been reported to increase sensitivity to AURKB inhibitors but the mechanism of their contribution to sensitivity is poorly understood. Two commonly reported outcomes of AURKB inhibition are polyploidy and senescence, although their relationship is unclear....

Non-resolving, chronic inflammation (inflammaging) is believed to play an important role in aging and age-related diseases. The goal of this study was to determine if inflammation induced by necroptosis arising from the liver plays a role in chronic liver disease (CLD) and liver cancer in mice fed a western diet (WD). Necroptosis was induced in liver using two knockin (KI) mouse models that overexpress genes involved in necroptosis (Ripk3 or Mlkl) specifically in liver (i.e., hRipk3-KI and...

Preclinical rodent models are essential research tools for improving understanding of physiological aging processes in humans. However, the translatability of findings obtained leveraging rodent models to humans is limited, likely due in part to differences in macronutrient composition of the diets. Here, we investigated the impact of a 3-month diet intervention in old male C57BL/6JN mice in which the macronutrient composition was aligned with that of a midlife/older adult in the United States,...

Microglia exhibit both maladaptive and adaptive roles in the pathogenesis of neurodegenerative diseases and have emerged as a cellular target for central nervous system (CNS) disorders, including those affecting the retina. Replacing maladaptive microglia, such as those impacted by aging or over-activation, with exogenous microglia that can enable adaptive functions has been proposed as a potential therapeutic strategy for neurodegenerative diseases. To investigate microglia replacement as an...

Human foragers avoid noncommunicable diseases that are leading causes of mortality, partly because physically active lifestyles promote healthy aging. High activity levels also promote tissue damage accumulation from wear-and-tear, increase risk of injury and disability which compromise productivity, and reduce energetic investments in somatic maintenance given constrained energy expenditure. Constraints intensify when nutrient supply is limited and surplus energy is directed toward pathogen...

Cell growth and gene expression are heterogeneous processes at the single-cell level, leading to the emergence of multiple physiological states within bacterial populations. Aging is a known deterministic driver of growth asymmetry; however, its role in gene expression heterogeneity remains elusive. Here, we show that aging mother cells undergo a progressive decline in old pole activity, generating asymmetry in protein partitioning, gene expression, and cell morphology. We demonstrate that...

Redox-mediated posttranslational modification, as exemplified by protein S-nitrosylation, modulates protein activity and function in both health and disease. Here, we review recent findings that show how normal aging, infection/inflammation, trauma, environmental toxins, and diseases associated with protein aggregation can each trigger excessive nitrosative stress, resulting in aberrant protein S-nitrosylation and hence dysfunctional protein networks. These redox reactions contribute to the...