Aging & Longevity

Human populations are experiencing unprecedented growth and longevity with lingering knowledge gaps of the characteristics, mechanisms, and pathologies of senescence. Invasive measurements and long-term control conditions for longitudinal studies are infeasible, necessitating the need for surrogate animal models. Rats have short lifespans (2-3 years) with translatable cardiovascular systems, and Sprague Dawley microcirculatory preparations are key to studying the oxygen transport mechanisms...

Extracellular vesicles (EVs) are implicated in inter-organ communication, which becomes particularly relevant during aging and exercise. DNA methylation-based aging clocks reflect lifestyle and environmental factors, while regular exercise is known to induce adaptive responses, including epigenetic adaptations. Twenty individuals with High-fitness (aged 57.7 ± 9.8 years) and twenty Medium-Low-fitness (aged 57.5 ± 9.7 years) subjects provided blood samples. EVs were isolated from the samples...

Nucleotide availability is crucial for DNA replication and repair; however, the coordinating mechanisms in vivo remain unclear. Here, we show that the circadian clock in the liver controls the activity of the pentose phosphate pathway (PPP) to support de novo nucleotide biosynthesis for DNA synthesis demands. We demonstrate that disrupting the hepatic clock by genetic manipulation or mistimed feeding impairs PPP activity in male mice, leading to nucleotide imbalance. Such defects not only elicit...

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With the development of deep learning (DL) techniques, there has been a successful application of this approach to determine biological age from latent information contained in retinal images. Retinal age gap (RAG) defined as the difference between chronological age and predicted retinal age has been established previously to predict the age-related disease. In this study, we performed discovery genome-wide association analysis (GWAS) on the RAG using the 31,271 UK Biobank participants and...

CONCLUSIONS: The point prevalence of depression in this multisite sample of community-dwelling older adults in the United States was 6.2%, which varied significantly with demographic characteristics and comorbid conditions. Engagement in volunteering activities might help older adults to reduce their risk of depression.

The present study examines whether structural and functional variability in medial temporal lobe (MTL) neocortical regions correlate with individual differences in episodic memory and longitudinal memory change in cognitively healthy older adults. To address this question, older adults were administered a battery of neuropsychological tests on three occasions: the second occasion one month after the first test session, and a third session three years later. Structural and functional MRI data...

Understanding the impact of senescence on disease is limited by the lack of tools to lineage label senescent cells. In a recent Cell issue, Zhao et al. create mouse models to genetically manipulate and trace p16^(+) cells, identifying contrasting roles for senescent macrophages and endothelial cells (ECs) in liver fibrosis.

Golgi abnormalities have been linked to aging and age-related diseases, yet the underlying causes and functional consequences remain poorly understood. This study identifies the interaction between age-associated zinc deficiency and Golgi stress as a critical factor in cellular aging. Senescent Golgi bodies from human fibroblasts show a fragmented Golgi structure, associated with a decreased interaction of the zinc-dependent Golgi-stacking protein complex Golgin45-GRASP55. Golgi stress is...

CONCLUSIONS: To sum up, weight-adjusted-waist index levels were negatively associated with serum Klotho protein concentration and showed a stronger correlation than other obesity markers. Our findings indicated that WWI may be a predictor of reduced Klotho levels, and that controlling obesity in accordance with WWI may help lower the Klotho levels.

Neurodegenerative disorders (NDDs) have been prevalent for more than a decade, and the number of individuals affected per year has increased exponentially. Among these NDDs, Alzheimer's disease, which causes extreme cognitive impairment, and Parkinson's disease, characterized by impairments in motor activity, are the most prevalent. While few treatments are available for clinical practice, they have minimal effects on reversing the neurodegeneration associated with these debilitating diseases....

The central nervous system (CNS) is endowed with its own resident innate immune cells, the microglia. They constitute approximately 10% of the total cells within the CNS parenchyma and act as 'sentinels', sensing and mitigating any deviation from homeostasis. Nevertheless, under severe acute or chronic neurological injury or disease, microglia are unable to contain the damage, and the reparative activity of monocyte-derived macrophages (MDMs) is required. The failure of the microglia under such...

The mammalian dentate gyrus (DG) is involved in certain forms of learning and memory, and DG dysfunction has been implicated in age-related diseases. Although neurogenic potential is maintained throughout life in the DG as neural stem cells (NSCs) continue to generate new neurons, neurogenesis decreases with advancing age, with implications for age-related cognitive decline and disease. In this study, we used single-cell RNA sequencing to characterize transcriptomic signatures of neurogenic...

Declines in physical and cognitive function are common in older adults. The circulating enzyme glycosylphosphatidylinositol (GPI)-specific phospholipase D1 (GPLD1) is elevated after exercise and has been associated with improved cognitive function when administered to aged mice. The purpose of this study was to investigate the relationship between GPLD1 and both cognitive function and brain structure/function in older adults with either high or low levels of physical activity. Healthy men and...

Cinnamon, renowned for its aromatic flavor, represents one of the most widely used spices worldwide. Cinnamon is also considered beneficial to human health with therapeutic potential for treating various diseases, ranging from diabetes and cancer to neurodegenerative diseases. However, the mechanisms underlying cinnamon's health benefits remain elusive. It is also unclear whether cinnamon has any role in aging. Using C. elegans as a model, here we show that feeding worms cinnamaldehyde (CA), the...

Throughout the animal kingdom, several members of the basic helix-loop-helix (bHLH) family act as proneural genes during early steps of nervous system development. Roles of bHLH genes in specifying terminal differentiation of postmitotic neurons have been less extensively studied. We analyze here the function of 5 Caenorhabditis elegans bHLH genes, falling into 3 phylogenetically conserved subfamilies, which are continuously expressed in a very small number of postmitotic neurons in the central...

Accumulation of damaged biomolecules in body tissues is the primary cause of aging and age-related chronic diseases. Since this damage often occurs spontaneously, it has traditionally been regarded as untreatable, with typical therapeutic strategies targeting genes or enzymes being ineffective in this domain. In this report, we demonstrate that an antibody targeting the isoDGR damage motif in lung tissue can guide immune clearance of harmful damaged proteins in vivo, effectively reducing...

Understanding the complex biological process of aging is of great value, especially as it can help develop therapeutics to prolong healthy life. Predicting biological age from gene expression data has shown to be an effective means to quantify aging of a subject, and to identify molecular and cellular biomarkers of aging. A typical approach for estimating biological age, adopted by almost all existing aging clocks, is to train machine learning models only on healthy subjects, but to infer on...

Age-related macular degeneration (AMD) is a progressive disorder and the leading cause of central vision loss. Age is the most important risk factor, followed by genetics and smoking. However, ageing is a complex process, and biological age can deviate from chronological age between individuals and within different organ systems. Initially, we used machine learning to predict the biological age of the immune, cardiovascular, pulmonary, renal, musculoskeletal, metabolic and hepatic systems by...

Increased expression of the cyclin-dependent kinase inhibitor p16Ink4a (p16) is detected in neurons of human Alzheimer's disease (AD) brains and during normal aging. Importantly, selective eliminating p16-expressing cells in AD mouse models attenuates tau pathologies and improves cognition. But whether and how p16 contributes to AD pathogenesis remains unclear. To address this question, we tested whether induction of p16 expression in neurons exacerbates AD pathologies. We created a...