Aging & Longevity

Lysosomes signal through the epigenome to regulate longevity across generations

1 month ago
The epigenome is sensitive to metabolic inputs and is crucial for aging. Lysosomes act as a signaling hub to sense metabolic cues and regulate longevity. We found that lysosomal metabolic pathways signal through the epigenome to regulate transgenerational longevity in Caenorhabditis elegans. Activation of lysosomal lipid signaling and lysosomal adenosine monophosphate-activated protein kinase (AMPK) or reduction of lysosomal mechanistic target of rapamycin (mTOR) signaling increased the...
Qinghao Zhang

Empathy in mild cognitive impairment: a preliminary clinical comparative study in Southern Switzerland using the interpersonal reactivity index (IRI) and the story-based empathy task (SET)

1 month ago
CONCLUSION: These findings provide preliminary evidence of early empathy-related and theory of mind alterations in MCI, supporting the inclusion of social cognition assessments in standard neuropsychological protocols. The combined use of self-report and task-based instruments may enhance early identification of socio-emotional dysfunctions and inform personalized clinical interventions. The preliminary nature of this study is mainly due to the small sample size and the heterogeneous clinical...
L Arnaud

The nuclear pore complex connects energy sensing to transcriptional plasticity in longevity

1 month ago
As the only gateway governing nucleocytoplasmic transport, the nuclear pore complex (NPC) maintains fundamental cellular processes and deteriorates with age. However, the study of age-related roles of single NPC components remains challenging owing to the complexity of NPC composition. Here, we demonstrate that the central energy sensor, AMP-activated protein kinase (AMPK), post-translationally regulates the abundance of the nucleoporin NPP-16/NUP50 in response to nutrient availability and...
Yifei Zhou

D-galactose-induced aging and obese conditions contribute to aging and pathologies in dental pulp of male wistar rats

1 month ago
Our previous studies demonstrated that both D-galactose (D-gal)-mediated aging and high-fat diet (HF)-promoted obesity trigger inflammation, impair mitochondrial function in heart and brain, and disrupt bone homeostasis. However, the dental pulp pathologies in aging and obesity remain unclear. Insight into pulp biology under systemic conditions may facilitate strategies for maintaining pulp vitality. This study explored the effects of D-gal-mediated aging and HF-promoted obesity and...
Savitri Vaseenon

Ubiquitin precursor with C-terminal extension promotes proteostasis and longevity

1 month ago
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...
Selver Altin

Neutrophil-to-lymphocyte ratio in aging: Trends and clinical implications

1 month ago
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...
Francisco Alejandro Lagunas-Rangel

An integrated multi-omic natural history study of human development, sexual dimorphism, and the effects of trisomy 21

1 month ago
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...
Neetha Paul Eduthan

Machine learning and data-driven inverse modeling of metabolomics unveil key processes of active aging

1 month ago
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...
Jiahang Li

Herbal terpenoids activate autophagy and mitophagy through modulation of bioenergetics and protect from metabolic stress, sarcopenia and epigenetic aging

1 month ago
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...
Gabriele Civiletto

Ribonucleotide incorporation into mitochondrial DNA drives inflammation

1 month ago
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...
Amir Bahat

Functional assessments of short-term spatial memory in the Dog Aging Project identify strong associations with age that are not moderated by body mass

1 month ago
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,...
Stephanie H Hargrave

Glucagon receptor signaling is indispensable for the healthspan effects of caloric restriction in aging male mice

1 month ago
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...
Kassandra R Bruner

Association between preoperative frailty to adverse postoperative outcomes in older people undergoing elective spinal surgery: a prospective cohort study

1 month ago
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.
Yanhong Song
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