Aging & Longevity

The aim of this study was to explore and discuss efficient and effective mammalian models for Alzheimer's disease (AD). In this study, efficient AD models are characterized by a small body size, a short lifespan, and rapid development of the main pathology including amyloid plaque formation. Effective AD models are expected to exhibit not only the main pathology, but also co-pathology associated with other neurodegenerative diseases (e.g., Lewy body dementia), systemic disturbances such as...

CONCLUSION: Older adults shortly after an ischemic stroke can quickly learn to walk with a soft robot and retain substantial clinical and mobility improvements at follow-up.

The growing aging population and rising prevalence of dementia are driving increased demand for long-term care services and supports in the United States. People with dementia require substantial support and care, often from direct care workers in private homes, assisted living communities, and nursing homes. Despite their crucial role, these workers receive highly variable training, particularly in dementia care, and face significant work-related challenges including stress, injury, and...

Purpose: Contrast sensitivity (CS), the ability to see objects against their background, is an important component of visual function. The effect of contrast sensitivity impairment (CSI) on physical functioning (PF) is not well documented. Methods: This study obtained data from the Aging, Demographics, and Memory Study. Baseline CS was measured, and self-reported PF, activities of daily living (ADLs), and instrumental activities of daily living (IADLs) were assessed biennially. Results: The...

Osteoarthritis is a prevalent joint disease in the aging population. The hallmark of osteoarthritis is the degeneration of the joint cartilage, characterized by changes in chondrocytes including mitochondrial dysfunction. However, the precise mechanisms of how this affects chondrocyte homeostasis and whether such processes can be explored as therapeutic targets for osteoarthritis remain unclear. Here, we show that impaired mitochondrial function and disrupted cartilage matrix metabolism due to...

CONCLUSIONS: Our study highlights the important regulatory functions and close association with complex human traits of human eG4s that are highly conserved in the mammalian lineage.

Heart failure remains one of the 21st century's greatest unmet clinical and public health challenges. Heart failure is a highly prevalent chronic condition that affects approximately 55 million people worldwide. Although heart failure can be prevented, the global burden of this condition continues to grow, fuelled by an ageing population, improved survival after myocardial infarction, and increasing prevalence of metabolic and kidney disease. Public health efforts for cardiovascular disease...

Understanding how amyloid beta (Aβ) plaques develop and lead to neurotoxicity in Alzheimer's disease remains a major challenge, particularly given the temporal delay and weak correlation between plaque deposition and cognitive decline. This study investigates how the evolving pathology of plaques affects the surrounding tissue, using a knock-in Aβ mouse model (App^(NL-F/NL-F)). We combined mass spectrometry imaging with stable isotope labeling to timestamp Aβ plaques from the moment of their...

Osteoporosis, primarily characterized by low bone mineral density (LBMD), is a major skeletal disorder among postmenopausal women (PMW), yet its global burden remains poorly quantified. Leveraging data from the Global Burden of Disease (GBD) Study 2021, we assessed the LBMD burden in PMW across 204 countries and territories between 1990 and 2021. Metrics included deaths, disability-adjusted life years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs), with temporal...

Nicotinamide adenine dinucleotide (NAD^(+)) is a critical metabolic co-enzyme implicated in brain aging, and augmenting NAD^(+) levels in the aging brain is an attractive therapeutic strategy for neurodegeneration. However, the molecular mechanisms of brain NAD^(+) regulation are incompletely understood. In cardiac tissue, the circadian nuclear receptor REV-ERBα has been shown to regulate NAD^(+) via control of the NAD^(+)-producing enzyme NAMPT. Here we show that REV-ERBα controls brain NAD^(+)...

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Dysregulated proteostasis is a hallmark of aging. We investigated how efficiently proteostatic adaptations to chronic cardiac cyclic-adenosine-monophosphate (cAMP)-dependent stress change with aging in mice harboring marked cardiac-specific over-expression of adenylyl cyclase VIII (TG^(AC8)). We assessed protein quality control mechanisms (PQC) (ubiquitin proteasome system, autophagic flux via macroautophagy, and mitophagy) in left ventricles of TG^(AC8) and wild-type littermates (WT) at 3-4 and...

CONCLUSIONS: People with lower levels of visual scanning behavior were more likely to suffer recurrent falls over time. This highlights the importance of visual function and behavior in mitigating fall risk and suggests that efforts to improve visual scanning may help to prevent recurrent falls in older adults.

Repetitive transcranial magnetic stimulation (rTMS) is an attractive tool to promote healthy brain ageing in older adults and treat age-related neurological conditions. Despite its popularity, the neurological processes and plasticity mechanisms altered by rTMS in the aged brain, and where these changes occur in the brain are unknown. Furthermore, it is not known why different rTMS protocols induce different changes in the aged brain, or why rTMS is less effective in older adults compared to...

CONCLUSIONS: Within the limits of this observational study, we conclude that in community-dwelling older adults, aging alters the prevalence and pattern of reported Long COVID.

Metabolomics has been associated with cognitive decline and dementia, but the relationship between metabolites and brain aging remains unclear. We aimed to investigate the associations of metabolomics with brain age assessed by neuroimaging and to explore whether these relationships vary according to apolipoprotein E (APOE) ε4. This study included 17,770 chronic brain disorder-free participants aged 40-69 years from UK Biobank who underwent neuroimaging scans an average of 9 years after...

The complexity of epigenetic changes that accompany aging has been distilled into a number of molecular timepieces-termed epigenetic clocks-that characterize the pace of biological aging to differing degrees. Here, we develop and validate a DNA methylation-based Physiological health Age (PhysAge) score, comprised of eight DNA methylation surrogates to represent multi-system physiology and developed from commonly measured clinical biomarkers: CRP, peak flow, pulse pressure, HDL-cholesterol,...

Kidney function declines progressively with age, with chronic kidney disease (CKD) affecting more than half of community-dwelling older adults. Identifying risk factors beyond the established ones (such as diabetes and hypertension) is crucial for prevention. Frailty and malnutrition are prevalent in older adults, yet the effect of these factors on their decline of kidney function remains underexplored. This study aimed to elucidate the associations between frailty, malnutrition, and renal...

CONCLUSION: Higher consumption of UPFs is positively associated with accelerated biological aging, with adiposity measures serving as significant mediators.

Inflamm-aging is widely considered a hallmark of aging, yet emerging evidence challenges its universality. Here, we re-examine inflamm-aging through an eco-evolutionary lens, underlining its context dependence across biological scales. Combining mechanistic, evolutionary, comparative, anthropological, genetic, and environmental evidence, we show how fundamental inflammatory mechanisms are integrated and regulated in diverse biological contexts, representing a suite of flexible stress responses....