Aging & Longevity

Rapamycin, also known as sirolimus, has demonstrated great potential for application in longevity medicine. However, the dynamics of low-dose rapamycin bioavailability, and any differences in bioavailability for different formulations (e.g., compounded or commercial), remain poorly understood. We thus explored rapamycin bioavailability in two real-world cohorts to begin providing a foundational understanding of differences in effects between formulations over time. The small trial study cohort...

Biological brain age is a brain-predicted age using machine learning to indicate brain health and its associated conditions. The presence of an older predicted brain age relative to the actual chronological age is indicative of accelerated aging processes. Consequently, the disparity between the brain's chronological age and its predicted age (brain-age gap) and the factors influencing this disparity provide critical insights into cerebral health dynamics during aging. In this study, we employed...

A healthy diet is a key determinant of successful aging. However, the psychological, social, and physiological changes associated with ageing often disrupt dietary behaviours. Hungary has one of the highest rates of chronic age-related diseases in the European Union, exacerbated by unhealthy dietary patterns and rapid population aging. This study evaluates attitudes and barriers to healthy eating among older adults in a socioeconomically disadvantaged region of Hungary, identifying determinants...

Over the past five years, systemic NAD^(+) (nicotinamide adenine dinucleotide) decline has been accepted to be a key driving force of aging in the field of aging research. The original version of the NAD World concept was proposed in 2009, providing an integrated view of the NAD^(+)-centric, systemic regulatory network for mammalian aging and longevity control. The reformulated version of the concept, the NAD World 2.0, was then proposed in 2016, emphasizing the importance of the inter-tissue...

Alternative splicing impacts most multi-exonic human genes. Inaccuracies during this process may have an important role in ageing and disease. Here, we investigate splicing accuracy using RNA-sequencing data from >14k control samples and 40 human body sites, focusing on split reads partially mapping to known transcripts in annotation. We show that splicing inaccuracies occur at different rates across introns and tissues and are affected by the abundance of core components of the spliceosome...

CONCLUSIONS: Superaging brains manifested maintained neurobiological youthfulness in terms of a more youthful brain aging status and a reduced speed of brain aging. These findings suggest that cognitive resilience, and potentially broader functional resilience, exhibited by superagers during the aging process may be attributable to their younger brains.

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.

No abstract

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...