Aging & Longevity

CONCLUSION: The global burden of Parkinson's disease has risen over the past 32 years, and there is a need to focus on key populations, as well as to improve health policies to prevent and treat Parkinson's disease.

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Prostate cancer is a heterogeneous disease with a slow progression and a highly variable clinical outcome. The tumor suppressor genes PTEN and TP53 are frequently mutated in prostate cancer and are predictive of early metastatic dissemination and unfavorable patient outcomes. The progression of solid tumors to metastasis is often associated with increased cell plasticity, but the complex events underlying TP53-loss-induced disease aggressiveness remain incompletely understood. Using genetically...

Inflammaging, a state of chronic low-grade inflammation associated with aging, has been linked to the development and progression of various disorders. Cellular senescence, a state of irreversible growth arrest, is another characteristic of aging that contributes to the pathogenesis of cardiovascular pathology. Senescent cells accumulate in tissues over time and secrete many inflammatory mediators, further exacerbating the inflammatory environment. This senescence-associated secretory phenotype...

Atherosclerosis and aortic aneurysms are prevalent cardiovascular diseases in the elderly, characterized by chronic inflammation and oxidative stress. This study explores the role of CircXYLT1 in regulating oxidative stress and vascular remodeling in age-related vascular diseases. RNA sequencing revealed a significant upregulation of CircXYLT1 in the vascular tissues of aged mice, highlighting its potential role in age-related vascular diseases. Using a carotid artery wire injury model, we...

Single-point mutations are pivotal in molecular zoology, shaping functions and influencing genetic diversity and evolution. Here we study three such genetic variants of a mechano-responsive protein, cadherin-23, that uphold the structural integrity of the protein, but showcase distinct genotypes and phenotypes. The variants exhibit subtle differences in transient intra-domain interactions, which in turn affect the anti-correlated motions among the constituent β-strands. In nature, the variants...

Telomere shortening ultimately causes replicative senescence. However, identifying the mechanisms driving replicative senescence in cell populations is challenging due to the heterogeneity of telomere lengths and the asynchrony of senescence onset. Here, we present a mathematical model of telomere shortening and replicative senescence in Saccharomyces cerevisiae which is quantitatively calibrated and validated using data of telomerase-deficient single cells. Simulations of yeast populations,...

Objective and subjective aging indicators reflect diverse biological and psychosocial processes, yet their combined association with premature mortality remains underexplored. This study aimed to investigate the association between a multidomain framework of aging indicators and premature mortality, addressing gaps in understanding cumulative effects. We included 369,741 UK Biobank participants initially free of cardiovascular disease (CVD) and cancer, followed until December 31, 2022. Four...

CONCLUSION: Age and TUG could only weakly explain ADL changes, while vision, hand grip strength, cognition, and age had moderate predictive ability of IADL. Therefore, by assessing these predictors, we can predict disability before it occurs and make necessary interventions.

Maintaining balance while simultaneously performing other tasks is common during everyday activities. However, this dual-tasking (DT) divides attention and increases cognitive demand, which can be detrimental to stability in older adults. It is unknown if the focus of attention influences how a dual-task affects balance and whether this is detectable in middle-aged adults. This study investigates the effect of dual-task and attentional focus on prefrontal cortex (PFC) activity in young (YA) and...

CONCLUSIONS: The serum levels of PF4 were decreased in AD patients and were significantly correlated with the cognitive function and CSF levels of Aβ42 and t-tau. PF4 may become a promising anti-aging and therapeutic target for AD, which is worthy of further study.

The association between male infertility and health status has yet to be unraveled. Here, by combining multiparameter phenotyping and scRNA-seq, we delineate the immune status of infertile men both at the semen and systemic levels. We first observe that young infertile men have a pro-inflammatory milieu with increased frequency of myeloid cells and inflammatory mediators in the seminal fluid and the peripheral blood, which are immune alterations typically observed in healthy elderly men....

Regulator of cell death-1 (RCD-1) governs the heteroallelic expression of RCD-1-1 and RCD-1-2, a pair of fungal gasdermin (GSDM)-like proteins, which prevent cytoplasmic mixing during allorecognition and safeguard against mycoparasitism, genome exploitation, and deleterious cytoplasmic elements (e.g., senescence plasmids) by effecting a form of cytolytic cell death. However, the underlying mechanisms by which RCD-1 acts on the cell membrane remain elusive. Here, we demonstrate that RCD-1 binds...

Sarcopenia and cancer cachexia are two life-threatening conditions often misdiagnosed. The skeletal muscle is one of the organs most adversely affected by these conditions, culminating in poor quality of life and premature mortality. In addition, it has been suggested that chemotherapeutic agents exacerbate cancer cachexia, as is the case of doxorubicin. Herein, we sought to investigate markers of inflammation and neuromuscular junction (NMJ) remodeling during aging and in response to cancer or...

Benign prostatic hyperplasia (BPH), characterized as a chronic disease with unregulated enlargement of prostatic gland, is commonly observed in elderly men leading to lower urinary tract dysfunction. Sestrin2 plays a role in the maintenance of cellular homeostasis and protects organisms from various stimuli. The exact role of Sestrin2 in the etiology of BPH, a common age-related disease, remains unknown. Here, we explored the regulatory function of Sestrin2 in modulating autophagy and its...

The nematode C. elegans has long served as a gold-standard model organism in aging research, particularly since the discovery of long-lived mutants in conserved aging pathways including daf-2 (IGF1) and age-1 (PI3K). Its short lifespan and small size make it highly suitable for high-throughput experiments. While numerous molecules have been tested for their effects on C. elegans lifespan, consensus is still lacking regarding the most effective and reproducible compounds. Confounding effects,...

The developmental theory of ageing proposes that age-specific decline in the force of natural selection results in suboptimal levels of gene expression in adulthood, leading to functional senescence. This theory explicitly predicts that optimising gene expression in adulthood can ameliorate functional senescence and improve fitness. Reduced insulin/IGF-1 signalling (rIIS) extends the reproductive lifespan of Caenorhabditis elegans at the cost of reduced reproduction. Here, we show that...

Ribosomal RNA is the main component of the ribosome, which is essential for protein synthesis. The diploid human genome contains several hundred copies of the rDNA transcription unit (TU). Droplet digital PCR and deep bisulfite sequencing were used to determine the absolute copy number (CN) and the methylation status of individual rDNA TU in blood samples of healthy individuals. The absolute CN ranged from 243 to 895 (median 469). There was no difference in absolute CN between males and females...

In this study, we investigated age-related changes in clinical laboratory data and their association with mortality in dogs from the Golden Retriever Lifetime Study. By analyzing complete blood count (CBC) and biochemistry data from 2'412 Golden Retrievers over 16,678 visits, we observed significant changes during the first 2 years of life and throughout aging. Based on these observations, we developed a biological aging clock using a LASSO model to predict age based on blood markers, achieving...

The question of what mechanisms maintain tropical biodiversity is a critical frontier in ecology, intensified by the heightened risk of biodiversity loss faced in tropical regions. Ecological theory has shed light on multiple mechanisms that could lead to the high levels of biodiversity in tropical forests. But variation in species abundances over time may be just as important as overall biodiversity, with a more immediate connection to the risk of extirpation and biodiversity loss. Despite the...