Aging & Longevity

People living with HIV are at higher risk of heart failure and associated left atrial remodeling compared to people without HIV. Mechanisms are unclear but have been linked to inflammation and premature aging. Here we obtain plasma proteomics concurrently with cardiac magnetic resonance imaging in two independent study populations to identify parallels between HIV-related and aging-related immune dysfunction that could contribute to atrial remodeling and clinical heart failure. We discover a...

An emerging biomarker of blood-brain barrier (BBB) permeability is the time of exchange (Tex) of water from the blood to tissue, as measured by multi-echo arterial spin labeling (ASL) MRI. This new non-invasive sequence, already tested in mice, has recently been adapted to humans and optimized for clinical scanning time. In this study, we studied the normal variability of Tex over age and sex, which needs to be established as a reference for studying changes in neurological disease. We evaluated...

Alzheimer's disease (AD) is a progressive neurodegenerative disorder in which there is slow and gradual impairment of mental function. Considering the increase in cases due to population aging, the potential benefits of physical training in AD are of great importance and need further elucidation. This study aims to identify the impact of physical training on crucial aspects of AD such as cognitive status, physical performances, quality of life and activities of daily living. The bibliographic...

CONCLUSION: This cross-sectional study reveals significant correlations between sleep quality and key factors such as physiological status, community participation, and daily functional activities in older adults with dynapenia. These findings underscore the importance of addressing these determinants to enhance sleep quality in this population.

CONCLUSIONS: Nearly 8%, or an estimated 1 million community-ambulating U.S. older adults, had severe impairments in peak expiratory flow in 2015; these older adults have a substantially higher risk of losing the ability to ambulate community distances over the subsequent year.

CONCLUSION: Under typical United States practice, cataract surgery for older patients was not significantly associated with cognitive improvement or decline in the year after, compared with the year before, surgery.

Age-related cognitive impairment and dementia pose a significant global health, social, and economic challenge. While Alzheimer's disease (AD) has historically been viewed as the leading cause of dementia, recent evidence reveals the considerable impact of vascular cognitive impairment and dementia (VCID), which now accounts for nearly half of all dementia cases. The Mediterranean diet-characterized by high consumption of fruits, vegetables, whole grains, fish, and olive oil-has been widely...

Rheumatoid arthritis (RA) is an age-related chronic inflammatory disease which may include accelerated biological ageing processes in its pathogenesis. To determine if increased biological age is associated with risk of RA and/or is present once disease is established. We used DNA methylation to compare biological age (epigenetic age) of immune cells in adults at risk of RA and those with confirmed RA, including twins discordant for RA. The established RA studies were secondary analyses of...

Gut microbiota plays a crucial role in the host health in the aging process. However, the mechanisms for how gut microbiota triggers cellular senescence and the consequent impact on human aging remain enigmatic. Here we show that phenylacetylglutamine (PAGln), a metabolite linked to gut microbiota, drives host cellular senescence. Our findings indicate that the gut microbiota alters with age, which leads to increased production of phenylacetic acid (PAA) and its downstream metabolite PAGln in...

CONCLUSION: The findings of this study underscore the necessity of policies and institutional measures grounded in community networks to mitigate the risk of all-cause mortality among vulnerable groups with persistently poor HLST.

Coronavirus disease 2019 (COVID-19) poses significant risks for solid organ transplant recipients, who have atypical but poorly characterized immune responses to infection. We aim to understand the host immunologic and microbial features of COVID-19 in transplant recipients by leveraging a prospective multicenter cohort of 86 transplant recipients age- and sex-matched with 172 non-transplant controls. We find that transplant recipients have higher nasal SARS-CoV-2 viral abundance and impaired...

Spinal muscular atrophy (SMA) is a progressive disease that affects motor neurons, with symptoms usually starting in infancy or early childhood. Recent breakthroughs in treatments targeting SMA have improved both lifespan and quality of life for infants and children with the disease. Given the impact of these treatments, it is essential to develop methods for managing treatment-induced changes in disease characteristics. Zolgensma® is the first effective and approved gene therapy for SMA caused...

Three monoclonal antibodies directed against specific forms of the amyloid-β (Aβ) peptide have been granted accelerated or traditional approval by the FDA as treatments for Alzheimer disease, representing the first step towards bringing disease-modifying treatments for this disease into clinical practice. Here, we review the detection, underlying pathophysiological mechanisms and clinical implications of amyloid-related imaging abnormalities (ARIA), the most impactful adverse effect of anti-Aβ...

In single cells, variably sized nanoscale chromatin structures are observed, but it is unknown whether these form a cohesive framework that regulates RNA transcription. Here, we demonstrate that the human genome is an emergent, self-assembling, reinforcement learning system. Conformationally defined heterogeneous, nanoscopic packing domains form by the interplay of transcription, nucleosome remodeling, and loop extrusion. We show that packing domains are not topologically associated domains....

The proteasome degrades most superfluous and damaged proteins, and its decline is associated with many diseases. As the proteolytic unit, the 20S proteasome is assembled from 28 subunits assisted by chaperones PAC1/2/3/4 and POMP; then, it undergoes the maturation process, in which the proteolytic sites are activated and the assembly chaperones are cleared. However, mechanisms governing the maturation remain elusive. Here, we captured endogenous maturation intermediates of human 20S proteasome,...

C-Terminal cyclic imides are posttranslational modifications that can arise from spontaneous intramolecular cleavage of asparagine or glutamine residues resulting in a form of irreversible protein damage. These protein damage events are recognized and removed by the E3 ligase substrate adapter cereblon (CRBN), indicating that these aging-related modifications may require cellular quality control mechanisms to prevent deleterious effects. However, the factors that determine protein or peptide...

OBJECTIVES: To examine the association of social connections with blood leukocyte telomere length (LTL) and all-cause mortality in older Costa Ricans.

The decline of oocyte quality with advanced maternal age has a detrimental effect on female fertility. However, there is limited knowledge of therapeutic options and their mechanisms to improve oocyte quality in reproductively older women. In this study, we demonstrated that supplementation of salidroside improves the oocyte quality of reproductively old mice. Salidroside improved the maturation, fertilization, and developmental competence of oocytes from reproductively old mice by maintaining...

The current mechanism by which aging reduces salivary secretion is unknown. This study investigates the mechanism of aging-related submandibular (SMG) dysfunction and evaluates the therapeutic potential of dental pulp stem cell-derived exosomes (DPSC-exos). We found that the stimulated salivary flow rate was significantly reduced in naturally aging and D-galactose-induced aging mice (D-gal mice) compared to control mice. Acinar atrophy and periductal fibrosis in SMGs and parotid glands (PGs)...

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