Aging & Longevity
Full-length direct RNA sequencing reveals extensive remodeling of RNA expression, processing and modification in aging Caenorhabditis elegans
Organismal aging is marked by decline in cellular function and anatomy, ultimately resulting in death. To inform our understanding of the mechanisms underlying this degeneration, we performed standard RNA sequencing (RNA-seq) and Oxford Nanopore Technologies direct RNA-seq over an adult time course in Caenorhabditis elegans. Long reads allowed for identification of hundreds of novel isoforms and age-associated differential isoform accumulation, resulting from alternative splicing and terminal...
Metabolic scaling, energy allocation tradeoffs, and the evolution of humans' unique metabolism
All organisms use limited energy to grow, survive, and reproduce, necessitating energy allocation tradeoffs, but there is debate over how selection impacted metabolic budgets and tradeoffs in primates, including humans. Here, we develop a method to compare metabolic rates as quotients of observed relative to expected values for mammals corrected for size, body composition, environmental temperature, and phylogenetic relatedness. Contrary to previous analyses, these quotients reveal that nonhuman...
Muscle fibroblasts and stem cells stimulate motor neurons in an age and exercise-dependent manner
Exercise preserves neuromuscular function in aging through unknown mechanisms. Skeletal muscle fibroblasts (FIB) and stem cells (MuSC) are abundant in skeletal muscle and reside close to neuromuscular junctions, but their relative roles in motor neuron maintenance remain undescribed. Using direct cocultures of embryonic rat motor neurons with either human MuSC or FIB, RNA sequencing revealed profound differential regulation of the motor neuron transcriptome, with FIB generally favoring neuron...
A small-molecule screen identifies novel aging modulators by targeting 5-HT/DA signaling pathway
The risk of many human diseases including cardiovascular diseases, cancer, neurodegenerative diseases, and musculoskeletal disorders rises significantly in the elderly. With the increase in the aging population, it is becoming increasingly important to understand the biology of healthy aging and develop interventions that slow down the aging process or prevent age-related diseases. In this study, by a high-throughput screen in Caenorhabditis elegans (C. elegans), we identified 11 small molecules...
The catabolic - anabolic cycling hormesis model of health and resilience
A major goal of aging research is to identify ways of extending productive and disease-free lifespans. Here we present the catabolic - anabolic cycling hormesis (CACH) model for optimizing health. The CACH model is based on the concept that cells and organ systems respond to catabolic challenges in ways that bolster their resilience and that an anabolic recovery period is required to effectuate the benefits of the catabolic challenge. As two prominent real-world examples we highlight the...
Early life exercise impacts physiology and lifespan in a sex- and genotype-dependent manner in a Drosophila melanogaster exercise model
Exercise is a common strategy for disease prevention or management, including for diabetes and cardiac dysfunction. However, exercise response varies immensely between individuals, and in humans, the same exercise treatment can lead both to positive and negative responses. Drosophila melanogaster is an established model for exercise research that can be leveraged to understand this variation in exercise response. Here, we investigated how two early life exercise treatments differing in duration...
The art of aging gracefully
No abstract
Compromised CD8+ T cell immunity in the aged brain increases severity of neurotropic coronavirus infection and postinfectious cognitive impairment
Advanced age increases the risk of severe disease from SARS-CoV-2 infection, as well as incidence of long COVID and SARS-CoV-2 reinfection. We hypothesized that perturbations in the aged antiviral CD8^(+) T cell response predisposes elderly individuals to severe coronavirus infection, re-infection, and postinfectious cognitive sequelae. Using MHV-A59 as a murine model of respiratory coronavirus, we found that aging increased CNS infection and lethality to MHV infection. This was coupled with...
Single cell and spatial transcriptomics highlight the interaction of club-like cells with immunosuppressive myeloid cells in prostate cancer
Prostate cancer treatment resistance is a significant challenge facing the field. Genomic and transcriptomic profiling have partially elucidated the mechanisms through which cancer cells escape treatment, but their relation toward the tumor microenvironment (TME) remains elusive. Here we present a comprehensive transcriptomic landscape of the prostate TME at multiple points in the standard treatment timeline employing single-cell RNA-sequencing and spatial transcriptomics data from 120 patients....
EZH2 inhibition sensitizes retinoic acid-driven senescence in synovial sarcoma
Synovial sarcoma (SS) is driven by a unique t(18;X) chromosomal translocation resulting in expression of the SS18-SSX fusion oncoprotein, a transcriptional regulator with both activating and repressing functions. However, the manner in which SS18-SSX contributes to the development of SS is not entirely known. Here, we show that SS18-SSX drives the expression of Preferentially Expressed Antigen in Melanoma (PRAME), which is highly expressed in SS but whose function remains poorly understood. The...
Adverse drug reactions and its associated factors among geriatric hospitalized patients at selected comprehensive specialized hospitals of the Amhara Region, Ethiopia: a multicenter prospective cohort study
CONCLUSIONS: This study found that over one-third of older people and individuals admitted to the hospital experienced ADRs. Overweight, hyperpolypharmacy, and patients who had previously been admitted during the preceding six months were significantly linked with the occurrence of ADRs. Improving the drug safety of elderly patients, particularly those who are admitted, should be a greater priority for healthcare professionals.
The relationship and heterogeneity of family participation and social participation among older adults: from an intersectionality perspective
Participation in late life has been studied as a component of active aging. To effectively promote late-life participation, the study explored the relationship and heterogeneity between two forms of participation among older adults-familial participation and societal participation. This paper utilizes data from the 2020 China Longitudinal Aging Society Survey (CLASS) to examine the relationship between familial participation and societal participation among older Chinese adults. Linear...
Neuropsychology of sexuality in older adults: bridging gaps in literature and future directions in research
Sexuality is a fundamental part of human existence and it encompasses thoughts, desires, behaviors, relationships, as well as neuropsychological and physiological components. However, sexuality in older adults is under-researched from the neuropsychological and psychophysiological perspectives and is often neglected by healthcare providers in the clinical practice. This article aims to explore the state of the art on the neuropsychology and psychophysiology of older adults' sexuality, proposing...
Influence of individual's age on the characteristics of brain effective connectivity
Given the increasing number of older adults in society, there is a growing need for studies on changes in the aging brain. The aim of this research is to investigate the effective connectivity of different age groups using resting-state functional magnetic resonance imaging (fMRI) and graph theory. By examining connectivity in different age groups, a better understanding of age-related changes can be achieved. Lifespan pilot data from the Human Connectome Project (HCP) were used to examine...
The Multi-State Epigenetic Pacemaker enables the identification of combinations of factors that influence DNA methylation
Epigenetic clocks, DNA methylation-based predictive models of chronological age, are often utilized to study aging associated biology. Despite their widespread use, these methods do not account for other factors that also contribute to the variability of DNA methylation data. For example, many CpG sites show strong sex-specific or cell-type-specific patterns that likely impact the predictions of epigenetic age. To overcome these limitations, we developed a multidimensional extension of the...
Standing balance test for fall prediction in older adults: a 6-month longitudinal study
CONCLUSION: In clinical practice in which only stance time is recorded, it is possible to interchangeably use the double-leg or semi-tandem stance. To identify early signs of imbalance, we suggest setting a time limit for the balance test equal to or greater than 23 s, as 10 s appear to be insufficient to detect subtle balance deficits. The time maintenance on tandem and single-leg positions was able to predict future falls.
Comparison of the oral health status of nursing home residents using the current and the newly developed interRAI oral health section (OHS-interRAI): a cross-sectional study
CONCLUSIONS: More missing OHS-interRAI data may be attributed to regulatory decisions on using the interRAI LTCF instrument. Caregivers identified more oral health problems with the OHS-interRAI, which may be due to its additional features, such as photographs and extensive instructions. The Collaborative Action Points included in the OHS-interRAI support continuity of care and enable integration of oral care into general care. Further research is needed to evaluate whether the OHS-interRAI...
Calcineurin/NFAT inhibitors maintain cognition in a preclinical prevention study in an aging canine model of Alzheimer disease
Brain signaling of calcineurin (CN) and nuclear factor of activated T-cells (NFAT) transcription factor increases in Alzheimer disease (AD) and is associated with synaptic loss, neurodegeneration, neuroinflammation, amyloid-β (Aβ) production, and cognitive decline. CN/NFAT inhibitors ameliorate these neuropathologies in mouse models of AD. Further, chronic use of tacrolimus in transplant patients reduces risk of AD. Beagles naturally develop Aβ plaques and cognitive dysfunction. We evaluated the...
Semaglutide as a possible therapy for healthy aging: Targeting the hallmarks of aging
With an aging population, the investigation of therapies that promote healthy aging becomes increasingly urgent. Here we discuss how Semaglutide can be a potential therapy to contribute to this goal by targeting key hallmarks of aging, such as inflammation, oxidative stress and stem cell exhaustion.
Age-related loss of intestinal barrier integrity plays an integral role in thymic involution and T cell ageing
The intestinal epithelium serves as a physical and functional barrier against harmful substances, preventing their entry into the circulation and subsequent induction of a systemic immune response. Gut barrier dysfunction has recently emerged as a feature of ageing linked to declining health, and increased intestinal membrane permeability has been shown to promote heightened systemic inflammation in aged hosts. Concurrent with age-related changes in the gut microbiome, the thymic...
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