Aging & Longevity

No abstract

The global population is ageing and the gap between lifespan (total years lived) and healthspan (years lived free of diseases) is increasing. Healthy Longevity Medicine (HLM) is an approach to optimise health and healthspan, and it has substantial public health implications. Despite those implications, the understanding of public perspectives on this field is lacking. The HEalthy LOngevity (HELO) framework was developed through a literature review guided by expert discussions across disciplines...

As the world population ages, new molecular targets in aging and Alzheimer's disease (AD) are needed to combat the expected influx of new AD cases. Until now, the role of RNA structure in aging and neurodegeneration has largely remained unexplored. In this study, we examined human hippocampal postmortem tissue for the formation of RNA G-quadruplexes (rG4s) in aging and AD. We found that rG4 immunostaining strongly increased in the hippocampus with both age and with AD severity. We further found...

Telomeres shorten with each cell division, acting as a chronometer of cell age. The enzyme telomerase, primarily active in stem cells, reverses telomere erosion. We have previously observed that transient transfection with human TERT mRNA extends telomeres and mitigates hallmarks of senescence in replicatively aged human cells or those affected by Hutchinson-Gilford progeroid syndrome (HGPS). However, due to its short half-life, mRNA requires frequent administration. In this study, we...

Intensive efforts have been made to identify features that could serve as biomarkers of aging. Yet, drug-based interventions aimed at lessening the detrimental effects of getting older are lacking. This is largely attributable to tissue-specificity, sex-related differences, and to the difficulty of identifying actionable targets, which continues to pose a significant challenge. Here, we implement a bioinformatics approach revealing that aging-associated increase of the transmembrane...

Myxomatous mitral valve degeneration (MMVD) is one of the most important age-dependent degenerative heart valve disorders in both humans and dogs. It is characterized by the aberrant remodeling of extracellular matrix (ECM), regulated by senescent myofibroblasts (aVICs) transitioning from quiescent valve interstitial cells (qVICs), primarily under TGFB1/TGF-β1 control. In the present study, we found senescent aVICs exhibited impaired macroautophagy/autophagy as evidenced by compromised autophagy...

Many aging cohort studies have collected data on participants' job titles, yet these job titles were seldom analyzed within the cognitive aging context despite their relevance to neurocognition, due to difficulties in analyzing these job titles quantitatively. While it is possible to rate these jobs' occupational complexity (OC) using job classification systems, this can be somewhat labor-intensive and prone to human errors. To this end, we demonstrate a novel and simple method to extract OC...

Musculoskeletal disorders are a significant public health burden concern, projected to increase in the coming decades, and will substantially contribute to the rising prevalence of functional impairment, frailty and disability in a growing global population. Since persons with musculoskeletal disorders tend to have immune dysfunction, inflammation or be taking immunosuppressive medication, prevention of vaccine-preventable diseases (VPDs) in this group is particularly important. The European...

In male mammals, spermatogonial stem cells (SSCs) are essential for sustaining lifelong spermatogenesis within the testicular open niche, a unique environment that allows SSC migration over an extended niche area. As SSCs undergo continuous mitotic division, mutations accumulate and are transmitted to the descendant SSC clones. Therefore, SSC clonal fate behaviors, in terms of their efficiencies in completing spermatogenesis and undergoing expansion within the niche, influence sperm genomic...

This study aimed to provide a complete characterization of age group differences in cortical lobar, hippocampal, and subcortical gray matter microstructure using a multi-compartment diffusion-weighted MRI (DWI) approach with parameters optimized for gray matter (Neurite Orientation Dispersion and Density Imaging, NODDI). 76 younger (undergraduate students) and 64 older (surrounding communities) adults underwent diffusion-, T1-, and susceptibility-weighted MRI. Results revealed eight unique...

Aging is the leading risk factor for Alzheimer's Disease (AD). Understanding the intricate interplay between biological aging and the AD pathophysiology may help to discover innovative treatments. The relationship between aging and core pathways of AD pathogenesis (amyloidopathy and tauopathy) have been extensively studied in preclinical models. However, the potential discordance between preclinical models and human pathology could represent a limitation in the identification of new therapeutic...

CONCLUSION: Our study highlights the ubiquity of frailty and cognitive impairment in older adults and underscores the heightened risk of mortality associated with their coexistence. These findings suggest the critical need for proactive screening and management of frailty and cognitive function in clinical practice to improve outcomes for the older adults.

Senescent cells accumulate in most tissues with organismal aging, exposure to stressors, or disease progression. It is challenging to identify senescent cells because cellular senescence signatures and phenotypes vary widely across distinct cell types and tissues. Here we developed an analytical algorithm that defines cell-type-specific and universal signatures of cellular senescence across a wide range of cell types and tissues. We utilize 72 mouse and 64 human weighted single-cell...

Aging increases brain susceptibility to neurodegenerative diseases, but the mechanisms are not clear. Vocal behavior provides an accessible, reliable, and sensitive biomarker to address this because voice changes in middle age can be early indicators of neurodegenerative diseases. The adult male zebra finch is an excellent model organism for these studies due to well-characterized vocal brain circuitry and strong homology to human brain centers. We performed RNA sequencing of song-dedicated...

Cellular senescence, a characteristic feature of the aging process, is induced by diverse stressors. In recent years, glaucoma has emerged as a blinding ocular disease intricately linked to cellular senescence. The principal pathways implicated are oxidative stress, mitochondrial dysfunction, DNA damage, autophagy impairment, and the secretion of various senescence- associated secretory phenotype factors. Research on glaucoma-associated cellular senescence predominantly centers around the...

The accumulation of senescent cells within tissues promotes the aging process by remodelling the functions of the immune system. For many years, it has been known that senescent cells secrete pro-inflammatory cytokines and chemokines, a phenotype called the senescence-associated secretory phenotype (SASP). Chemokines and colony-stimulating factors stimulate myelopoiesis and recruit myeloid cells into aging tissues. Interestingly, recent studies have demonstrated that senescent cells are not only...

Cellular senescence is a stress response that limits tumor formation by promoting the removal of damaged cells through the immune system. In this study, we observed accumulation of senescent cells during human aging gingival tissue, by increased levels of γH2A.X, 53BP1, and SAHF, along with a greater distance of H3K9me3 from the nuclear periphery. Additionally, primary gingival fibroblasts from older individuals displayed an enlarged nuclear area and perimeter, accompanied by DNA damage...

Understanding the impact of early vascular aging (EVA) on acute ischemic stroke (AIS) outcomes may provide new insights for improving prognostic assessments and developing targeted therapeutic strategies. This study aimed to validate the EVA ambulatory score (EVAAs) in AIS patients, assessing its association with stroke type, severity, and prognosis. Among the 2,730 AIS patients with a mean age of 72.0 ± 14.4 years, 83.4% exhibited EVA. EVA was identified as an independent predictor of poor...

eccDNA is a driver of many cancers and a potential intermediate in other age-related disorders. However, little is known about the mechanisms underlying eccDNA formation in healthy tissue and how aging affects these processes. Here, we present an atlas of eccDNA across seven tissues of male mice spanning four ages. EccDNA correlates with open chromatin characterized by signatures of H3K27ac and H3K4me1. Additionally, the mutational load of eccDNA on genes correlates with tissue-specific...

Ageing is associated with cognitive decline, which is a significant factor in the development of dementia. Vitamin B12 (VB12) is crucial for maintaining proper nervous system function, as well as for protein, fat, and carbohydrate metabolism, and DNA synthesis. Moreover, it helps prevent serious health conditions such as pernicious anemia, neurodegenerative diseases, and Alzheimer's disease. VB12 deficiency is common among the elderly population. We found that serum VB12 levels were...