Aging & Longevity

Age is an independent risk factor for atherosclerotic cardiovascular disease that increases the susceptibility of older adults to vascular intimal thickening, endothelial dysfunction, and thrombosis. However, the mechanism underlying vascular injury is not fully understood. In the present study, the effect of proprotein convertase subtilin-type kexin 9 (PCSK9) inhibitors on the senescent state of human umbilical vein endothelial cells (HUVECs) and on senescent mice and lipopolysaccharides (LPS)...

We derive and test a CT-based biological age model for predicting longevity, using an automated pipeline of explainable AI algorithms that quantifies skeletal muscle, abdominal fat, aortic calcification, bone density, and solid abdominal organs. We apply these AI tools to abdominal CT scans from 123,281 adults (mean age, 53.6 years; 47% women; median follow-up, 5.3 years). The final weighted CT biomarker selection was based on the index of prediction accuracy. The CT model significantly...

Autophagic mechanisms that maintain nuclear envelope homoeostasis are bulwarks to ageing and disease. Here we define a quantitative and ultrastructural timeline of nuclear macroautophagy (nucleophagy) in yeast by leveraging four-dimensional lattice light sheet microscopy and correlative light and electron tomography. Nucleophagy begins with a rapid accumulation of the selective autophagy receptor Atg39 at the nuclear envelope and finishes in ~300 s with Atg39-cargo delivery to the vacuole....

Observational studies suggest a link between biological aging and adverse pregnancy outcomes (APOs), but causal relationships remain unclear. This study aimed to investigate the relationship between genetically predicted biological aging traits and APOs. Genetic summary statistics from the genome-wide association study (GWAS) of the IEU open GWAS, FinnGen, and meta-analysis were analyzed using Mendelian randomization (MR) to infer causality. Biological aging indicators included facial aging,...

Aging is a physiological/pathological process accompanied by progressive impairment of cellular function, leading to a variety of aging-related diseases. STAT3 is one of the core regulatory factors of aging. It is involved in body metabolism, development and senescence, cell apoptosis and so on. During the aging process, the changes of growth factors and cytokines will cause the activation of STAT3 to varying degrees, regulate the inflammatory pathways related to aging, regulate body...

Aging is a complex and heterogeneous biological process characterized by telomere attrition, genomic instability, mitochondrial dysfunction, and disruption in nutrient sensing. Besides contributing to the progression of cancer, metabolic disorders, and neurodegenerative diseases, these manifestations of aging also adversely affect organ function. It is crucial to understand these mechanisms and identify interventions to modulate them to promote healthy aging and prevent age-related diseases....

Aging is associated with a disruptive decline in gastrointestinal health leading to decreased duodenal cell proliferation ultimately affecting the digestive and absorptive capacity of intestines in all species. This study investigates the novel application of blood plasma therapy to enhance duodenal cell proliferation associated with aging. In the presented study, the effects of middle aged plasma therapy on the aged rat duodenum were investigated. For this purpose, using a randomized controlled...

Current deep-learning-based image-analysis solutions exhibit limitations in holistically capturing spatiotemporal cellular changes, particularly during aging. We present scCamAge, an advanced context-aware multimodal prediction engine that co-leverages image-based cellular spatiotemporal features at single-cell resolution alongside cellular morphometrics and aging-associated bioactivities such as genomic instability, mitochondrial dysfunction, vacuolar dynamics, reactive oxygen species levels,...

CONCLUSION: Our study demonstrates that patterning potential decreases over time and aging imposes restrictions on preliminary neural patterning. These results emphasize the significance of patterning in the nervous system and the close relationship between patterning and fate determination, raising questions about the application of aged NSPCs in the treatment of neurodegenerative diseases.

CONCLUSION: Urinary CX3CL1 levels correlate with the aging process and may serve as a potential diagnostic biomarker for both amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD).

Adults with Down syndrome are genetically predisposed to developing Alzheimer's disease after the age of 40. The cholinergic system, which is critical for cognitive functioning, is known to decline in Alzheimer's disease and although first investigated in individuals with Down syndrome 40 years ago, remains relatively understudied. Existing studies suggest individuals with Down syndrome have an intact cholinergic system at birth that declines through adulthood alongside the development of...

Recent discoveries have shown that systemic manipulation, such as parabiosis, blood exchange, and young plasma transfer, can counteract many hallmarks of aging. This rejuvenation effect has been attributed to circulatory factors produced by cells from both hematopoietic and non-hematopoietic lineages. However, the specific involvement of bone marrow (BM) or hematopoietic cells in producing such factors and their effects on aging is still unclear. We developed a model of aged mice with...

In neurons, the quantities of mRNAs and proteins are traditionally assumed to be determined by functional, electrical or genetic factors. Yet, there may also be global, currently unknown computational rules that are valid across different molecular species inside a cell. Surprisingly, our results show that the energy for molecular turnover is a significant cellular expense, en par with spiking cost, and which requires energy-saving strategies. We show that the drive to save energy determines...

Pancreatic ductal adenocarcinoma has a dismal prognosis. A comprehensive analysis of single-cell multi-omic data from matched tumour-infiltrated CD45+ cells and peripheral blood in 12 patients, and two published datasets, reveals a complex immune infiltrate. Patients have either a myeloid-enriched or adaptive-enriched tumour microenvironment. Adaptive immune cell-enriched is intrinsically linked with highly distinct B and T cell clonal selection, diversification, and differentiation. Using TCR...

An artificial intelligence (AI)-enabled electrocardiogram (ECG) model has been developed in a healthy adult population to predict ECG biological age (ECG-BA). This ECG-BA exhibited a robust correlation with chronological age (CA) in healthy adults and additionally significantly enhanced the prediction of aging-related diseases' onset in adults with subclinical diseases. The model showed particularly strong predictive power for cardiovascular and non-cardiovascular diseases such as stroke,...

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BACKGROUND: Fall is a major health threat to older people. The lower-limb power and rate of torque or force development (RTD or RFD) are prominently affected by aging and are crucial for maintaining postural balance. However, there have been inconsistent findings regarding the association of such aspects of lower-limb strength with falls among community-dwelling older adults. Comprehensive synthesis and appraisal are needed to examine what deficits in lower-limb rapid force generation could...

In most eukaryotic organisms, cells that rely on continuous cell division employ the enzyme telomerase which replenishes chromosome termini through the addition of telomeric repeats. In budding yeast, the telomerase holoenzyme is composed of a catalytic core associated with two regulatory subunits, Est1 and Est3. The Est1 protein binds a telomere-specific RPA-like complex to recruit telomerase to chromosome ends. However, the regulatory function of the Est3 subunit has remained elusive. We...

The ubiquitin kinase and ligase PINK1 and PRKN together label damaged mitochondria for their elimination in lysosomes by selective autophagy (mitophagy). This cytoprotective quality control pathway is genetically linked to familial Parkinson disease but is also altered during aging and in other neurodegenerative disorders. However, the molecular mechanisms of these mitophagy changes remain uncertain. In healthy mitochondria, PINK1 protein is continuously imported, cleaved, and degraded, but...

Aging increases the susceptibility to metabolic dysfunction-associated steatotic liver disease (MASLD). Liver sinusoidal endothelial cells (LSECs) help in maintaining hepatic homeostasis, but the contribution of age-associated LSECs dysfunction to MASLD is not clear. The aim of this study was to investigate the effect of aging-associated LSECs dysfunction on MASLD. Free fatty acid-treated AML12 cells were co-cultured with young and etoposide-induced senescent TSEC cells to evaluate the...