Aging & Longevity

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...

There is a growing interest in developing drugs with a general geroprotective effect, aimed at slowing down aging. Several compounds have been shown to increase the lifespan and reduce the incidence of age-related diseases in model organisms. Translating these results is challenging, due to the long lifespan of humans. To address this, we propose using a battery of medical imaging protocols that allow for assessments of age-related processes known to precede disease onset. These protocols, based...

Extender of chronological lifespan 1 (Ecl1) inhibits target of rapamycin complex 1 (TORC1) and is necessary for appropriate cellular responses to various stressors, such as starvation, in fission yeast. However, little is known about the effect of posttranslational modifications on Ecl1 regulation. Thus, we investigated the phosphorylation levels of Ecl1 extracted from yeast under conditions of sulfur or metal starvation. Mass spectrometry analysis revealed that Ecl1 was phosphorylated at Thr7,...

Propionate metabolism dysregulation has emerged as a source of metabolic health alterations linked to aging, cardiovascular and renal diseases, obesity and diabetes, and cancer. This is supported by several large cohort population studies and recent work revealing its role in cancer progression. Mutations in several enzymes of this metabolic pathway are associated with devastating inborn errors of metabolism, resulting in severe methylmalonic and propionic acidemias. Beyond these rare diseases,...

Brown adipose tissue (BAT) is the primary site for non-shivering thermogenesis in the body and plays a crucial role in maintaining core body temperature. However, its function gradually declines with age. To mitigate the age-related decline in BAT thermogenic capacity, we treated progeroid mice with metformin to investigate the potential mechanisms by which metformin can slow the reduction in BAT thermogenic function. We found that progeroid mice, after receiving metformin treatment, showed...

Aging is associated with several physiological changes, including a remarkable remodeling of the immune system. Herein, the rhythms and shifts in serum immune mediators were characterized in a decade lifespan as a longitudinal community-based prospective investigation from Bambuí Health and Aging Study. The study population included paired samples from 713 subjects survivors from the original BHAS cohort and at 10-years Follow-up, categorized into 5-years age range intervals (60-64^(Yrs) towards...

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Aging leads to progressive decline in organ and tissue integrity and function, partly due to loss of proteostasis and autophagy malfunctioning. A decrease with age in chaperone-mediated autophagy (CMA), a selective type of lysosomal degradation, has been reported in various organs and cells from rodents and humans. Disruption of CMA recapitulates features of aging, whereas activating CMA in mice protects against age-related diseases such as Alzheimer's, retinal degeneration and/or...

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The locus coeruleus (LC) is a brainstem nucleus that provides the primary source of noradrenaline (NA) in the nervous system and optimizes behavioral performance in mammals. In humans, the LC shows Alzheimer's disease (AD)-like pathology at its earliest stages, but little is known about LC integrity in normative, non-pathological aging. The present research addresses these gaps by investigating neuron numbers, densities of glia and vasculature, and volume of the LC itself in cognitively assessed...

Circadian rhythms control the diurnal nature of many physiological, metabolic, and immune processes. We hypothesized that age-related impairments in circadian rhythms are associated with high susceptibility to bacterial respiratory tract infections. Our data show that the time-of-day difference in the control of Streptococcus pneumoniae infection is altered in elderly mice. A lung circadian transcriptome analysis revealed that aging alters the daily oscillations in the expression of a specific...

The elderly face elevated mortality risk due to rising temperature. Previous assessments of temperature-related mortality, however, lack a comprehensive analysis of distinct impacts of temperature change across different timescales and characteristics. Using a longitudinal survey of 27,233 elderly Chinese citizens from 2005 to 2018, we establish connections between rising temperatures, temperature variability, and extreme heat with increased mortality risk, assessed through four annual metrics...

The ovarian reserve defines female reproductive lifespan, which in humans spans decades due to the maintenance of meiotic arrest in non-growing oocytes (NGOs) residing in primordial follicles. Unknown is how the chromatin state of NGOs is established to enable long-term maintenance of the ovarian reserve. Here, we show that a chromatin remodeler, CHD4, a member of the Nucleosome Remodeling and Deacetylase (NuRD) complex, establishes chromatin states required for formation and maintenance of the...

CONCLUSIONS: Higher and increasing MVPA over time is associated with better neuropsychiatric health in individuals aged ≥ 70 years. Future studies should prioritize evaluating detailed PA trajectories to better understand how different doses, intensities, and modalities of PA impact neuropsychiatric decline in older adults.