Aging & Longevity

CONCLUSION: The ML results indicate that two tree-based methods (RF and GB) are reliable and effective as initial models for classification tasks involving discrete clinical aging and neurodegeneration data. In the XAI phase, SHAP performed better than LIME due to lower computational time (when applied to RF and GB) and incorporation of feature interactions, leading to more reliable results.

This review focuses on sexual dimorphism in cellular senescence and senolytic treatment in relation to brain health and age-related cognitive decline. The stressors of aging, DNA damage, inflammation, and oxidative stress induce cell senescence, a hallmark of aging. Senescent cells change their function and molecular profile and are primed to release pro-inflammatory cytokines. The functional changes include the activation of cell signals to prevent cell death. The release of pro-inflammatory...

INTRODUCTION: Neurophysiological activity, as noninvasively captured by electro- and magnetoencephalography (EEG and MEG), demonstrates complex temporal fluctuations approximated by typical variations around the mean values and rare events with large amplitude. The statistical properties of these extreme and rare events in neurodynamics may reflect the limits or capacity of the brain as a complex system in information processing. However, the exact role of these extreme neurodynamic events in...

Understanding the trajectory of in vivo locus coeruleus (LC) signal intensity across the adult lifespan and among various demographic groups, particularly during middle age, may be crucial for early detection of neurodegenerative diseases, which begin in the LC decades before symptom onset. Even though pathological changes in the LC are thought to begin in middle age, its characteristics across the adult lifespan, and its consistency and variation across demographic groups, remain not well...

Regulatory T cells (Tregs) are important in maintaining tolerance and are key players in immunity. In aging, increased Treg function along with low-grade inflammation has been reported. This dichotomy of enhanced Treg function along with inflammation highlights the importance of understanding Treg biology and communication patterns in the very old. In this proof-of-concept study, we demonstrate that aged Tregs (85 years) do not significantly communicate with CD4^(+) and CD8^(+) T effectors when...

Neuronal mitochondrial function is critical for orchestrating inter-tissue communication essential for overall fitness. Despite its significance, the molecular mechanism underlying the impact of prolonged mitochondrial stresses on neuronal activity and how they orchestrate metabolism and aging remains elusive. Here, we identified the evolutionarily conserved transmembrane protein XBX-6/TMBIM-2 as a key mediator in the neuronal-to-intestinal mitochondrial unfolded protein response (UPRmt). Our...

The detrimental effects of lockdowns have already been proven by numerous studies, mainly using psychometric measurements. Since telomere shortening is a driver of aging and aging-associated disorders, including cognitive decline, the telomere length in the older population has been investigated in the current study. Measurements were taken over a 6-month period just before and during the 6 months that included the first lockdown. The cohort of 55 persons aged 64 to 70 years was investigated in...

Insomnia is a common sleep disorder characterized mainly by poor sleep quality and insufficient sleep duration. It affects a significant proportion of the global population and is correlated with physical and mental consequences such as cognitive decline, anxiety, chronic fatigue, poor concentration, and memory impairment. Interestingly, it is also linked to ageing and age-related diseases (cardiovascular, metabolic, and neurodegenerative). On the other hand, as we age, DNA methylation patterns...

Aging is the risk factor for chronic pancreatitis and severity determinant for its acute attack, yet the underlying cause is unclear. Here, we demonstrate that senescent β-cells of endocrine pancreas decide the onset and severity of chronic and acute pancreatitis. During physiological aging, senescent β-cells increase the expression of miR-503-322 which is secreted as small extracellular vesicles to enter exocrine acinar cells, driving a causal and reversible role on aging-associated...

While most people contain Mycobacterium tuberculosis infection, some individuals develop active disease, usually within two years of infection. Why immunity fails after initially controlling infection is unknown. C57BL/6 mice control Mycobacterium tuberculosis for up to a year but ultimately succumb to disease. We hypothesize that the development of CD4 T cell dysfunction permits bacterial recrudescence. We developed a reductionist model to assess antigen-specific T cells during chronic...

Changes in nuclear shape and in the spatial organization of chromosomes in the nucleus commonly occur in cancer, ageing and other clinical contexts that are characterized by increased DNA damage. However, the relationship between nuclear architecture, genome organization, chromosome stability and health remains poorly defined. Studies exploring the connections between the positioning and mobility of damaged DNA relative to various nuclear structures and genomic loci have revealed nuclear and...

CONCLUSIONS: An association between falls and depression was observed. Depressive symptoms were associated with an increased risk of falls, even after controlling for other co-factors. The CIT method leveraged us to select the most important variables to predict falls with great precision. To prevent and manage falls among the expanding and diverse older-aged population, a multilevel and cross-sectoral approach is required. Mental health, especially depression, should be dealt with greater...

CONCLUSIONS: Our findings suggest that excess weight may have a varying effect on cancer risk through life with its impact potentially being more pronounced in later adulthood, and that adulthood weight gain might be a better indicator of obesity-related cancer risk than BMI measured at a single point in time.

UV exposure leads to skin damage, thus inducing skin aging. The aims of this study were to explore the differences in tRNA-derived small RNAs (tsRNAs) expression in the Human dermal fibroblasts (HDF cells) photoaging cell model and to explore the biological functions of tsRNA in skin photoaging. In this study, we found that in both photoaging cell models and the skin of photoaging mice, the 5'-tiRNA-His-GTG expression levels were significantly elevated. In HDF cells, overexpression of...

The accumulation of senescent cells contributes to aging and related diseases; therefore, discovering safe senolytic agents-compounds that selectively eliminate senescent cells-is a critical priority. Heat shock protein 90 (HSP90) inhibitors (HSP90i), traditionally investigated for cancer treatment, have shown potential as senolytic agents. However, inhibitors face formulation, toxicity, and cost challenges. To overcome these limitations, we employed a virtual screening approach combining...

CONCLUSIONS: Our findings highlight the need for tailored treatment strategies for older breast cancer patients to balance treatment efficacy with quality-of-life considerations. These findings call for a strategic reevaluation of treatment protocols and emphasize the importance of personalized care, particularly for older women, to improve outcomes without sacrificing the quality of life while maintaining maximum survival potential.

INTRODUCTION: Inadequate primary care infrastructure and training in China and misconceptions about aging lead to high mis-/under-diagnoses and serious time delays for dementia patients, imposing significant burdens on family members and medical carers.

Healthy "environment-sleep-emotion-exercise-diet" intervention [E(e)SEEDi] lifestyle can improve the quality of life, prolong aging and promote longevity due to improvement of human immunity and prevention of cardiovascular diseases (CVD). Here, the author reviewed the associations between these core elements with CVD and cardiovascular aging, and developed a new scoring system based on the healthy E(e)SEEDi lifestyle for prediction and evaluation of life expectancy. These core factors are...

Gene expression (GE) and alternative splicing (AS) contribute to the formation of new interaction networks with potentially significant cellular functions. Here, we investigate ageing in the Drosophila female germline stem cell (GSC) niche and describe functional changes in both GE and AS. The GSC niche comprises three types of support cells, whose ageing transcriptomes reveal differential GE and AS variations related to cell adhesion, cytoskeleton and neural signalling. Because each population...

Mouse oocytes undergo drastic changes in organellar composition and their activities during maturation from the germinal vesicle (GV) to metaphase II (MII) stage. After fertilization, the embryo degrades parts of the maternal components via lysosomal degradation systems, including autophagy and endocytosis, as zygotic gene expression begins during embryogenesis. Here, we demonstrate that endosomal-lysosomal organelles form large spherical assembly structures, termed endosomal-lysosomal...