Aging & Longevity

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Ubiquitin is a conserved modifier regulating the stability and function of numerous target proteins. In all eukaryotes, polyubiquitin precursors are generated and processed into ubiquitin monomers. The final ubiquitin unit always contains a C-terminal extension, but its physiological significance is unknown. Here, we show that C-terminally extended ubiquitin, termed CxUb, is essential for stress resistance, mitophagy, and longevity in Saccharomyces cerevisiae and Caenorhabditis elegans. CxUb...

The neutrophil-to-lymphocyte ratio (NLR) has emerged as a widely accessible and cost-effective marker of systemic inflammation, derived from routine peripheral blood counts. It has demonstrated clinical relevance across a broad spectrum of conditions, including infections, cardiovascular disease, malignancies, trauma, postoperative complications, and cancer. Aging is associated with a gradual rise in NLR, driven by increasing neutrophil counts and declining lymphocyte numbers, reflecting...

Human development involves multiple signaling pathways acting concertedly in an age- and sex-specific fashion. Trisomy 21, the genetic cause of Down syndrome, dysregulates human development leading to both early neurodevelopmental delays and atypical accelerated aging through unknown mechanisms. Here, we report an integrated multi-omic analysis of the effects of age, sexual dimorphism, and trisomy 21 in hundreds of research participants using matched transcriptome, proteome, metabolome, and...

Physical inactivity and low fitness have become global health concerns. Metabolomics, as an integrative approach, may link fitness to molecular changes. In this study, we analyzed blood metabolomes from elderly individuals under different treatments. By defining two fitness groups and their corresponding metabolite profiles, we applied several machine learning classifiers to identify key metabolite biomarkers. Aspartate consistently emerged as a dominant fitness marker. We further defined a body...

Small molecular food components contribute to the health benefits of diets rich in fruits, vegetables, herbs and spices. The cellular mechanisms by which noncaloric bioactives promote healthspan are not well understood, limiting their use in disease prevention. Here, we deploy a whole-organism, high-content screen in zebrafish to profile food-derived compounds for activation of autophagy, a cellular quality control mechanism that promotes healthy aging. We identify thymol and carvacrol as...

Metabolic dysregulation can lead to inflammatory responses^(1,2). Imbalanced nucleotide synthesis triggers the release of mitochondrial DNA (mtDNA) to the cytosol and an innate immune response through cGAS-STING signalling³. However, how nucleotide deficiency drives mtDNA-dependent inflammation has not been elucidated. Here we show that nucleotide imbalance leads to an increased misincorporation of ribonucleotides into mtDNA during age-dependent renal inflammation in a mouse model lacking the...

Companion dogs have emerged as a valuable model in the study of cognitive aging, but assessments of cognitive function in large, diverse, and geographically distributed samples of dogs are challenging to obtain. We developed two novel functional assessments of short-term spatial memory that were administered by community science participants in a sample of 6,753 dogs through the Dog Aging Project. We compared data generated by community scientists to those gathered by research professionals,...

Obesity and type 2 diabetes mellitus accelerate aging, shortening the duration of healthspan. Conversely, chronic calorie restriction (CR) extends healthspan. Research aimed at understanding the mechanism by which CR slows aging has focused heavily on insulin and downstream signaling cascades. Glucagon, a hormone that counter-regulates insulin, is commonly affected by these same interventions. To investigate the role of glucagon in aging, we used dietary manipulation, global and liver-specific...

CONCLUSIONS: The central symptoms and their intricate connections in the network play an importance role in gaining the underlying pathological mechanisms, as well as potential interventions for comorbidity in community older adults.

CONCLUSIONS: In geriatric elective spine surgery, preoperative assessment using the Frailty Screening Scale can help identify patients at potentially higher risk for postoperative adverse events. However, further high-quality studies are warranted to investigate the reliability of brief frailty assessments in predicting postoperative outcomes.

CONCLUSION: S-AnthropoAge shows modest advantages over CA in correlating with key physical function measures (HGS, FTSST) and may complement CA in assessing functional aging.

CONCLUSION: The healthy working life expectancy at 60 years old in China exceeds the targeted retirement age of 65. Salient socioeconomic and geographic variations of healthy working life expectancy exist in China.

Cholangiocarcinoma (CCA) remains a lethal malignancy with limited therapeutic options. Through genome-wide CRISPR-Cas9 screening, we identified the adenosine triphosphatase (ATPase) valosin-containing protein (VCP) as a critical dependency in CCA. Compound screens revealed that the VCP inhibitor CB-5339 potently suppresses CCA proliferation in a panel of patient-derived organoids by inducing cellular senescence. It is known that senescent cells persist, and this can contribute to therapy...

Aging drives cognitive decline in the adult brain with unclear mechanisms. Previously, oligodendrocyte precursor cells (OPCs), the source cells of myelin-forming cells in the central nervous system, have been linked to brain aging by their compromised differentiation and regeneration capability. Whether a myelination-independent function of OPCs is involved in brain aging remains unknown. In this study, we herein report a myelination-independent role of OPCs in exaggerating cognitive decline in...

The retina is uniquely enriched in polyunsaturated fatty acids (PUFAs), primarily localized in cell membranes, where they govern membrane biophysical properties. During aging, alterations in lipid metabolism lead to reduced content of very long-chain PUFAs (VLC-PUFAs) in the retina, which is associated with normal age-related reductions in contrast sensitivity, diminished photoreceptor function and delayed rod-mediated dark adaptation recovery, and pathological age-related macular degeneration...

Clathrin-mediated endocytosis (CME) is a critical cellular process that regulates nutrient uptake, membrane composition, and signaling. Although replicative aging affects many cellular functions, its impact on CME remains largely unknown. We show that in budding yeast, older cells have slower assembly of early and coat CME modules, resulting in longer endocytic turnover and reduced Mup1 internalization. This change in CME dynamics is mother cell-specific, and not observed in daughters. Our data...

Heightened air pollution exposure is associated with an increased risk for developing neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease, yet it is unclear how pollution impacts the aging brain more broadly. Rodent research has shown that higher air pollution exposure is associated with increased impulsive behavior, operationalized as a preference for immediate reward in delay discounting tasks. We examined this relationship in middle-aged and older humans by...

Functional dedifferentiation, a hallmark of brain aging particularly evident within the frontoparietal network (FPN), has been extensively investigated in the context of cognitive decline, yet its implications for late-life mental health remain poorly understood. Leveraging naturalistic paradigm combined with gradient mapping techniques, the present study investigated FPN functional dedifferentiation-quantified by functional dispersion of FPN in the multidimensional gradient space-during...