Aging & Longevity

The aging population worldwide necessitates the development of novel therapeutics that enhance the quality of life by preventing and treating age-related diseases. In this review, we first discuss the advantages of a dual-purpose target identification strategy for aging and age-related diseases, with assessment of the hallmarks of aging as an approach to identify such dual-purpose targets. Resulting from a convergence of aging research with machine learning (ML) and other artificial intelligence...

Late-onset depression (LOD) is closely linked to Alzheimer's disease (AD), marked by shared biological pathways and common risk factors. The neurobiological alterations associated with depression, particularly the dysregulation of amyloid-β (Aβ), play a critical role in the acceleration of disease progression. In individuals suffering from LOD, Aβ peptides - specifically Aβ40 and Aβ42 - exhibit distinct profiles in plasma, cerebrospinal fluid (CSF), and brain tissue, highlighting the substantial...

Aging is a series of adverse changes over time that increases mortality risk. Several hypotheses have been proposed to explain aging, including Leslie Orgel's Error-Catastrophe Theory, which asserts that translation errors erode the translational machinery, become self-amplifying, and eventually lead to death. Evidence for the theory is scarce, especially regarding intra-specific fidelity-longevity correlations. Here, we demonstrate that the correlation can be hidden by the constrained evolution...

The immune system comprises multiple cell lineages and subsets maintained in tissues throughout the lifespan, with unknown effects of tissue and age on immune cell function. Here we comprehensively profiled RNA and surface protein expression of over 1.25 million immune cells from blood and lymphoid and mucosal tissues from 24 organ donors aged 20-75 years. We annotated major lineages (T cells, B cells, innate lymphoid cells and myeloid cells) and corresponding subsets using a multimodal...

Calorie restriction (CR) improves health and longevity. CR induces a periodic fasting cycle in mammals; our study compares CR with unanticipated fasting (F), when the food is unexpectedly withheld. F induces hepatic steatosis, whereas CR reduces it; surprisingly, the difference is not due to hepatic β-oxidation. Liver transcriptome analysis identifies fatty acid transporters (Slc27a1 and Slc27a2), triglyceride (TAG) synthesis (Gpat4), and lipid storage (Plin2 and Cidec) genes to be upregulated...

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Periodontitis, a prevalent inflammatory disease worldwide, poses a significant economic burden on society and the country. Previous research has established a connection between cellular senescence and periodontitis. However, the role and mechanism of cell senescence in the progression of periodontitis have not been thoroughly investigated. This study aimed to explore the involvement of cellular senescence in the pathogenesis of periodontitis and determine the underlying mechanisms. Our findings...

CONCLUSION: Oral and gut microbiota diversity showed significant differences between patients with recurrent pneumonia and common pneumonia pneumonia-infected patients. The higher prevalence of both S. aureus and K. pneumoniae in the oral microbiota offers crucial insights into the pneumonia etiology. Specifically, the increased abundance of K. pneumoniae may contribute significantly to the heightened lung infections susceptibility among elderly individuals.

CONCLUSIONS: In elderly patients, long-term (current) aspirin use is negatively associated with the incidence of SAD and is also linked to improved clinical outcomes.

Aging is increasingly understood not as the passive accumulation of molecular damage, but as the cumulative cost of unresolved physiological adaptation under bioenergetic constraint. This review introduces Exposure-Related Malnutrition (ERM) as a mechanistically grounded and clinically actionable phenotype of early maladaptation. ERM arises from sustained metabolic strain during chronic stress exposure and manifests not through overt weight loss or nutrient deficiency, but through subtle,...

Cytoskeleton-Associated Protein 4 (CKAP4) is a multifunctional protein implicated in diverse cellular processes, including cytoskeletal organization, signal transduction, and extracellular matrix remodeling. Recent studies have highlighted the dual role of CKAP4 in regulating cell growth and aging. On one hand, CKAP4 can promote cell proliferation and survival by activating signaling pathways such as PI3K/Akt, thereby delaying cellular senescence under physiological conditions. On the other...

Aging-related frailty increases the risk of falls, disability, and mortality. Frailty is linked to abnormalities in whole-body metabolism. However, the causal relationship between circulating metabolic traits and frailty remains unclear. This study aims to clarify the causal effects of circulating metabolites on frailty. We used bidirectional two sample and multivariable Mendelian Randomization (MVMR) methods to assess associations between circulating metabolites and the Frailty Index (FI)....

Brain health is increasingly recognized as a critical component of overall wellbeing, particularly concerning neurodegenerative diseases, which are characterized by the progressive degeneration of the nervous system. Conditions such as Alzheimer's disease (AD) and Parkinson's disease, together with less common disorders, resembling Amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD), significantly impact cognitive and physical health, affecting over 50 million individuals...

AIM: To investigate the dynamics of neuromotor functions from 6 to 80 years with the Zurich Neuromotor Assessment (ZNA) and to provide reference curves for clinical and research use.

Previous work showed that natural selection has acted to minimize the genomic frequencies of representative dynamic DNA sequences capable of forming G-quadruplex, Triplex, hairpin, and i-motif structures in long-lived mammals, thus diminishing the mutagenic potential of their genomes. This report extends findings with single sequences to broadly distributed G3-4N1-7G3-4N1-7G3-4N1-7G3-4 dynamic sequence motifs and identifies a second, previously unknown, pool of dynamic DNA sequences that escape...

Obesity-related conditions are among the leading causes of preventable death and are increasing in prevalence worldwide. Body size and composition are complex traits that are challenging to characterize due to environmental and genetic influences, longitudinal variation, heterogeneity between sexes, and differing health risks based on adipose distribution. Here, we construct a 4-factor genomic structural equation model using 18 measures, unveiling shared and distinct genetic architectures...

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The progressive loss of cerebral white matter during aging contributes to cognitive decline, but whether reduced blood flow is a cause or a consequence remains debatable. Using deep multi-photon imaging in mice, we examined microvascular networks perfusing myelinated tissues in cortical layer 6 and the corpus callosum. We identified sparse, wide-reaching venules, termed principal cortical venules, which exclusively drain deep tissues and resemble the vasculature at the human cortex and U-fiber...

Aging is a major risk factor in amyotrophic lateral sclerosis (ALS) and other adult-onset neurodegenerative disorders. Whereas young neurons are capable of buffering disease-causing stresses, mature neurons lose this ability and degenerate over time. We hypothesized that the resilience of young motor neurons could be restored by reexpression of the embryonic motor neuron selector transcription factors ISL1 and LHX3. We found that viral reexpression of ISL1 and LHX3 selectively in postnatal motor...

Cannabidiol (CBD), a non-psychoactive cannabinoid, has been studied for its various health-promoting effects recently. This study investigates the effects of dietary CBD to the circadian clock of Drosophila melanogaster as a model animal and its many physiological effect to flies. We showed that CBD extended the period of locomotor activity in a dose-dependent manner, suggesting its influence on the circadian clock. Additionally, CBD improved sleep quality and extended lifespan under starvation...