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Virus-mediated gene transfer of soluble amyloid precursor protein-alpha via systemic injection in a mouse model of Alzheimer's disease

3 days 19 hours ago
Alzheimer's disease (AD) is the most common neurodegenerative disorder, yet effective preventive or therapeutic strategies remain limited. A hallmark of AD pathology is the accumulation of insoluble amyloid-β (Aβ) aggregates, which are targeted by recent antibody-based therapies. Conversely, soluble amyloid precursor protein-alpha (sAPPα), a non-amyloidogenic cleavage product of APP, possesses neuroprotective, neurotrophic, and synaptogenic properties, and the ability to enhance memory. This...
Yuanyuan He

Integrative epigenomic landscape of Alzheimer's Disease brains reveals oligodendrocyte molecular perturbations associated with tau

3 days 19 hours ago
Alzheimer's disease (AD) brains have variable neuropathologic and biochemical changes. Capturing epigenetic factors associated with this variability can reveal novel biological insights into AD pathophysiology. Here, we conduct an epigenome-wide association study of DNA methylation in 472 AD brains with neuropathologic and biochemical brain protein levels core to AD pathogenesis. Using a novel regional methylation (rCpGm) approach, we identify 5478 significant associations, 99.7% of which...
Stephanie R Oatman

Piezo1-dependent activation of stromal cells ignites muscle inflammation in exercise and injury and is associated with inflammaging

3 days 19 hours ago
As the actuator of movement and a key regulator of organismal metabolism, skeletal muscle is a site at which inflammatory responses must be carefully calibrated to counteract stressors while preventing protracted functional impairments. Exercise, injury and aging are common forms of stress associated with inflammation; yet the specific inducers and sensors driving such inflammation remain poorly characterized. Multipronged assessment of acute and chronic endurance exercise models uncovered a...
P Kent Langston

Knowledge of lifespan and healthspan and interest in Healthy Longevity Medicine among the general population in Singapore: the Singapore HEalthy LOngevity (HELO) survey

3 days 19 hours ago
Given the growing global interest in Healthy Longevity Medicine (HLM), the field lacks understanding about public knowledge and interest, which are crucial for any public health intervention relying on HLM. This study presents findings from the Healthy Longevity (HELO) survey conducted in Singapore, assessing public knowledge regarding lifespan (number of years a person is alive), healthspan (number of years a person spends in good health), and interest in HLM. This nationwide cross-sectional...
Jonas John Posko Amalaraj

The gut microbiome and ageing trajectories: mechanisms and clinical implications

3 days 19 hours ago
This Review discusses the current state of knowledge on the contribution of the gut microbiome as a potential key actor in defining how we age. The gut microbiome is a complex ecosystem that establishes lifelong dynamic interactions with the host at multiple levels (several gut-organ axes), differently influencing ageing patterns and age-related disease onset and progression across populations. Accordingly, the definition of a 'normative' gut microbiome remains elusive, depending largely on the...
Andrea Ticinesi

Association of physical activity with incident dementia and cognitive decline among Australian older adults

3 days 19 hours ago
We investigated the association between physical activity (PA) intensity and dementia and cognitive decline in Australian community-dwelling older adults. This prospective cohort study uses data from 11,655 older adults (mean age (standard deviation, SD) = 75.0 (4.2) years, 53.4% females, 52.9% had completed ≥ 12 years of education), who were participants in the ASPirin in Reducing Events in the Elderly (ASPREE) clinical trial and its observational follow-on (ASPREE-XT) and the ASPREE...
Yang Chen

Aging and increased cancer risk: exploring the potential of LE8 score to mitigate risk

3 days 19 hours ago
Given global population aging and the absence of aging-reversal therapies, elucidating the aging-related cancer risk association and developing cancer prevention strategies are imperative. This population-based cohort study analyzed data from the UK Biobank. Aging was assessed through four validated markers, including Klemera-Doubal method (KDM), PhenoAge, leukocyte telomere length (TL) and chronological age. Over a median follow-up of 13.5 years, significant associations between all aging...
Jiehui Li

A hierarchy of causes of death in senescent C. elegans

3 days 19 hours ago
Interventions that extend lifespan in animal models could, in principle, decelerate the aging process as a whole. Alternatively, they could act by suppressing one or more individual late-life pathologies that contribute to mortality. Here we show how, in the nematode Caenorhabditis elegans, late-life pathologies can compete in a hierarchical fashion to cause death, such that removal of one cause of death can unmask another. Under standard culture conditions, a major cause of death in elderly C....
Hongyuan Wang

Multi-tissue transcriptomic aging atlas reveals predictive aging biomarkers in the killifish

3 days 19 hours ago
Aging is associated with progressive tissue dysfunction, leading to frailty and mortality. Characterizing aging features, such as changes in gene expression and dynamics, shared across tissues or specific to each tissue, is crucial for understanding systemic and local factors contributing to the aging process. We performed RNA sequencing on 13 tissues at six different ages in male and female African turquoise killifish, the shortest-lived vertebrate that can be raised in captivity. This...
Emma K Costa

Estropausal gut microbiota transplant improves measures of ovarian function in adult mice

3 days 19 hours ago
The decline in ovarian function with age affects fertility and is associated with increased risk of age-related diseases, including osteoporosis and dementia. Notably, earlier menopause is linked to shorter lifespan, yet the molecular mechanisms underlying ovarian aging remain poorly understood. Recent evidence suggests the gut microbiota may influence ovarian health. Here we show that ovarian aging is associated with distinct gut microbial profiles in female mice and that the gut microbiome can...
Minhoo Kim

Contested involvement of family members in service allocation processes in long-term care: a qualitative study

3 days 19 hours ago
CONCLUSIONS: By prioritising system efficiency over family members' values, New Public Management principles influence and obstruct the dynamics and effectiveness of family members' involvement in the long-term care allocation process. To improve and enhance the involvement of family members, a paradigm shift towards a more family-oriented approach within the long-term care system is needed.
Ann Katrin Blø Pedersen