Aging & Longevity
X*Y females exhibit steeper reproductive senescence in the African pygmy mouse
A wave of studies has recently emphasized the influence of sex chromosomes on both lifespan and actuarial senescence patterns across vertebrates and invertebrates. Basically, the heterogametic sex (XY males in XX/XY systems or ZW females in ZW/ZZ systems) typically displays a lower lifespan and a steeper rate of actuarial senescence than the homogametic sex. However, whether these effects extend to the senescence patterns of other phenotypic traits or physiological functions is yet to be...
Broad repression of DNA repair genes in senescent cells identified by integration of transcriptomic data
Cellular senescence plays a significant role in tissue aging. Senescent cells, which resist apoptosis while remaining metabolically active, generate endogenous DNA-damaging agents, primarily reactive oxygen species. Efficient DNA repair is therefore crucial in these cells, especially when they undergo senescence escape, resuming DNA replication and cellular proliferation. To investigate whether senescent cell transcriptomes reflect adequate DNA repair capacity, we conducted a comprehensive...
Subtypes of brain change in aging and their associations with cognition and Alzheimer's disease biomarkers
Structural brain changes underlie cognitive changes and interindividual variability in cognition in older age. By using structural MRI data-driven clustering, we aimed to identify subgroups of cognitively unimpaired older adults based on brain change patterns and assess how changes in cortical thickness, surface area, and subcortical volume relate to cognitive change. We tested (1) which brain structural changes predict cognitive change (2) whether these are associated with core cerebrospinal...
Vibrational fiber photometry: label-free and reporter-free minimally invasive Raman spectroscopy deep in the mouse brain
Optical approaches to monitor neural activity are transforming neuroscience, owing to a fast-evolving palette of genetically encoded molecular reporters. However, the field still requires robust and label-free technologies to monitor the multifaceted biomolecular changes accompanying brain development, aging or disease. Here, we have developed vibrational fiber photometry as a low-invasive method for label-free monitoring of the biomolecular content of arbitrarily deep regions of the mouse brain...
Aftereffect of single transcranial direct and alternating current stimulation on spontaneous home-cage and open-field EEG activities in a mouse model of Alzheimer's disease
CONCLUSION: This study provides insight into the short-term aftereffects of transcranial current stimulation in the aging and AD brain and is the first animal study to compare brain activity between tACS and tDCS treatments.
A high-protein diet-responsive gut hormone regulates behavioral and metabolic optimization in Drosophila melanogaster
Protein is essential for all living organisms; however, excessive protein intake can have adverse effects, such as hyperammonemia. Although mechanisms responding to protein deficiency are well-studied, there is a significant gap in our understanding of how organisms adaptively suppress excessive protein intake. In the present study, utilizing the fruit fly, Drosophila melanogaster, we discover that the peptide hormone CCHamide1 (CCHa1), secreted by enteroendocrine cells in response to a...
A microbiota-derived metabolite, 3-phenyllactic acid, prolongs healthspan by enhancing mitochondrial function and stress resilience via SKN-1/ATFS-1 in C. elegans
The mechanisms underlying the impact of probiotic supplementation on health remain largely elusive. While previous studies primarily focus on the discovery of novel bioactive bacteria and alterations in the microbiome environment to explain potential probiotic effects, our research delves into the role of living Lactiplantibacillus (formerly known as Lactobacillus) and their conditioned media, highlighting that only the former, not dead bacteria, enhance the healthspan of Caenorhabditis elegans...
Higher skeletal muscle mitochondrial oxidative capacity is associated with preserved brain structure up to over a decade
Impaired muscle mitochondrial oxidative capacity is associated with future cognitive impairment, and higher levels of PET and blood biomarkers of Alzheimer's disease and neurodegeneration. Here, we examine its associations with up to over a decade-long changes in brain atrophy and microstructure. Higher in vivo skeletal muscle oxidative capacity via MR spectroscopy (post-exercise recovery rate, k(PCr)) is associated with less ventricular enlargement and brain aging progression, and less atrophy...
Hidden route of protein damage through oxygen-confined photooxidation
Oxidative modifications can disrupt protein folds and functions, and are strongly associated with human aging and diseases. Conventional oxidation pathways typically involve the free diffusion of reactive oxygen species (ROS), which primarily attack the protein surface. Yet, it remains unclear whether and how internal protein folds capable of trapping oxygen (O(2)) contribute to oxidative damage. Here, we report a hidden pathway of protein damage, which we refer to as O(2)-confined...
Aging-induced immune microenvironment remodeling fosters melanoma in male mice via gammadelta17-Neutrophil-CD8 axis
Aging is associated with increased tumor metastasis and poor prognosis. However, how an aging immune system contributes to the process is unclear. Here, single-cell RNA sequencing reveals that in male mice, aging shifts the lung immune microenvironment towards a premetastatic niche, characterized by an increased proportion of IL-17-expressing γδT (γδ17) and neutrophils. Mechanistically, age-dependent downregulation of the immune trafficking receptor S1pr1 drives the expansion of γδ17. Compared...
GATD3A-deficiency-induced mitochondrial dysfunction facilitates senescence of fibroblast-like synoviocytes and osteoarthritis progression
Accumulating evidence indicates that cellular senescence is closely associated with osteoarthritis. However, there is limited research on the mechanisms underlying fibroblast-like synoviocyte senescence and its impact on osteoarthritis progression. Here, we elucidate a positive correlation between fibroblast-like synoviocyte senescence and osteoarthritis progression and reveal that GATD3A deficiency induces fibroblast-like synoviocyte senescence. Mechanistically, GATD3A deficiency enhances the...
Age-dependent regulation of axoglial interactions and behavior by oligodendrocyte AnkyrinG
The bipolar disorder (BD) risk gene ANK3 encodes the scaffolding protein AnkyrinG (AnkG). In neurons, AnkG regulates polarity and ion channel clustering at axon initial segments and nodes of Ranvier. Disruption of neuronal AnkG causes BD-like phenotypes in mice. During development, AnkG is also expressed at comparable levels in oligodendrocytes and facilitates the efficient assembly of paranodal junctions. However, the physiological roles of glial AnkG in the mature nervous system, and its...
Evaluation of the effects of thyroid functions on frailty in geriatric patients using the Edmonton, SOF and FRAIL Scales
CONCLUSION: This study highlights the significant impact of thyroid dysfunction on frailty in older adults. Lower fT3 levels and the fT3/fT4 ratio emerged as key indicators of increased frailty, particularly on the SOF and EFS scales. Subgroup analysis further emphasized the importance of age-specific assessments, with a lower fT3/fT4 ratio being a critical indicator of frailty in individuals aged ≥ 80 years, while lower TSH levels were significant in those aged < 80 years. Abnormal TSH levels...
Effector-dependent decline in strength and subcortical motor excitability with aging
A decline in upper limb strength is common with normal aging. However, whether age-related strength decline is paralleled by reduced excitability of descending motor pathways is unclear. The reticulospinal tract is a key subcortical pathway involved in gross motor output and exhibits increased excitability following resistance training. Here, we sought to determine age-related effects on strength and reticulospinal excitability in flexors and extensors of the upper limb in humans. In 15 younger...
Benefits of physical exercise through multivariate analysis in sedentary adults and elderly: An analysis of physical fitness, health and anthropometrics
This study employed multivariate analysis to investigate the effects of a 14-week multicomponent training program on sedentary adults and older populations, focusing on improvements in physical fitness, health markers, and anthropometric measures. The data included 376 participants aged 30 to 84 years who had been inactive for at least 3 months. Results showed that participants aged 71 and above had lower systolic blood pressure, height, body mass, elbow flexion and extension, sitting and...
A review of utility of wearable sensor technologies for older person frailty assessment
Frailty is one of the most concerning aspects of global population aging, and early identification is crucial to prevent or reverse its progression. Simple, universal, and efficient frailty assessment technologies are essential for the timely detection of frailty in older patients. Various multi-dimensional assessment instruments have been developed to quantify frailty phenotypes; we review the literature on wearable sensor technologies leveraged for older person frailty assessment. This review...
Aging-induced changes in lymphatic muscle cell transcriptomes are associated with reduced pumping of peripheral collecting lymphatic vessels in mice
Lymphatic muscle cells (LMCs) within the wall of collecting lymphatic vessels exhibit tonic and autonomous phasic contractions, which drive active lymph transport to maintain tissue-fluid homeostasis and support immune surveillance. Damage to LMCs disrupts lymphatic function and is related to various diseases. Despite their importance, knowledge of the gene transcriptional signatures in LMCs and how they relate to lymphatic function in normal and disease contexts is largely missing. We have...
Association of 3-year change in frailty index with risk of all-cause mortality among older Chinese population: a national cohort study
CONCLUSIONS: Excessive increase in FI was positively associated with an increased risk for all-cause mortality. Approaches to reducing FI may be of great significance in improving the health of older Chinese individuals.
Effectiveness and cost-effectiveness of a single home-based fall prevention program: a prospective observational study based on questionnaires and claims data
CONCLUSIONS: This fall prevention programme with a single home visit was found to be effective and cost effective. Health policies should establish such a model as a reimbursed standard care to assist in combatting the increasing burden of falls on individuals and societies.
Structural inequality linked to brain volume and network dynamics in aging and dementia across the Americas
Structural inequality, the uneven distribution of resources and opportunities, influences health outcomes. However, the biological embedding of structural inequality in aging and dementia, especially among underrepresented populations, is unclear. We examined the association between structural inequality (country-level and state-level Gini indices) and brain volume and connectivity in 2,135 healthy controls, and individuals with Alzheimer's disease and frontotemporal lobe degeneration from Latin...
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