Aging & Longevity

No abstract

Human positive coactivator 4 (PC4) is a highly abundant non-histone chromatin protein involved in diverse cellular processes, including transcription regulation, genome organization, autophagy, B-cell differentiation, neurogenesis, DNA repair, etc. Most PC4 is phosphorylated in cells, which interacts with core histones and the linker histone H1 to confer the compact heterochromatin state of the genome. Knocking down PC4 at both cellular and organismal levels leads to significant chromatin...

Cardiovascular diseases remain the leading cause of mortality worldwide, with aging as a major risk factor. Endothelial cell (EC) dysfunction, driven by cellular senescence, is central to age-related cardiomyopathy. Despite its clinical significance, the molecular mechanisms underlying endothelial senescence remain incompletely defined. In this study, we observed that the expression of the endothelial-specific gene heat shock protein family A member 12B (HSPA12B) declines significantly with age....

CONCLUSION: The most significant differences between OXYS and Wistar blood metabolomes were found for 20-day-old animals, which corresponds to the preclinical period of AD development in humans. Metabolomic changes observed in the brain and blood are different and often opposite in sign. Blood serum is potentially promising fluid for AD diagnosis.

CONCLUSION: The developed prognostic scoring system provides a practical tool for predicting cognitive decline among adults aged 50 and older in Shanghai, China. The moderate discriminatory power and good calibration suggest that the model can effectively guide early interventions. Future research should validate the model in diverse populations and explore additional risk factors to enhance its predictive accuracy.

Biological sex is a crucial, but poorly understood variable in age-related susceptibility to infection. Monocytes are important immune cells responsible for initiating and resolving inflammatory responses to infection. While changes in monocyte populations result in increased susceptibility to infection, there is limited research on the impact of age and sex on human monocyte phenotype and function. The aim of this work was to dissect the impact of increasing age and biological sex on human...

Apraxia is a common symptom in Alzheimer's disease (AD) that reduces autonomy and quality of life. However, the neural basis underlying apraxia in AD, for example, reflected by functional connectivity (FC) alterations, remains unexplored. We investigated static and dynamic FC using resting-state functional imaging in 14 patients with biomarker-confirmed AD pathology and 14 matched healthy participants. FC was estimated as average (static) and short-term (dynamic) connectivity strengths between...

Taurine deficiency was recently proposed as a driver of aging in various species, including humans. To test this hypothesis, we assessed whether circulating taurine was associated with aging and physical performance in 137 physically inactive and physically active men aged 20-93. No association between circulating taurine levels and age, muscle mass, strength, physical performance, or mitochondrial function was observed, thereby challenging the implication of taurine deficiency as a primary...

Accurately identifying senescent cells is essential for studying their spatial and molecular features. We developed DeepScence, a method based on deep neural networks, to identify senescent cells in single-cell and spatial transcriptomics data. DeepScence is based on CoreScence, a senescence-associated gene set we curated that incorporates information from multiple published gene sets. We demonstrate that DeepScence can accurately identify senescent cells in single-cell gene expression data...

No abstract

Within each cell, metabolite-sensing factors respond to coordinate metabolic homeostasis. How metabolic homeostasis is regulated intercellularly and how this may become dysregulated with age, however, remains underexplored. Here we describe a system regulated by a metabolite sensor, CtBP2. CtBP2 is secreted via exosomes in response to reductive metabolism, which is suppressed by oxidative stress. Exosomal CtBP2 administration extends lifespan in aged mice and improves healthspan in particular by...

CONCLUSIONS: Lower levels of healthy aging were associated with higher mortality, particularly among older adults with lower educational attainment. These findings highlight the need for targeted strategies to promote healthy aging, especially among those with lower levels of education.

Granulosa cells (GCs) are the most dynamically responsive cell lineage to encourage continuous folliculogenesis; however, developmental dynamics and interplay with downstream transcription circuitry remain unclear. Here, we unravel the redistribution of genome-wide chromatin areas that drive broad developmental-related transcriptomic alterations during follicular maturation in murine and porcine GCs. Distinct GC-activated accessibility regions (GAAs) at the ovulatory phase are responsible for...

Mutations that occur in the cell lineages of sperm or eggs can be transmitted to offspring. In humans, positive selection of driver mutations during spermatogenesis can increase the birth prevalence of certain developmental disorders^(1-3). Until recently, characterizing the extent of this selection in sperm has been limited by the error rates of sequencing technologies. Here we used the duplex sequencing method NanoSeq⁴ to sequence 81 bulk sperm samples from individuals aged 24-75 years. Our...

As we age, many tissues become colonized by microscopic clones carrying somatic driver mutations^(1-7). Some of these clones represent a first step towards cancer whereas others may contribute to ageing and other diseases. However, our understanding of this phenomenon remains limited due to the challenge of detecting mutations in small clones. Here we introduce a new version of nanorate sequencing (NanoSeq)⁸, a duplex sequencing method with an error rate lower than five errors per billion base...

Aging occurs in a heterogeneous manner across different organs, leading to varying risks of chronic diseases and mortality. Biological age offers a more comprehensive reflection of the aging process and is a stronger predictor of disease risk and lifespan. Recent advances in plasma proteomics have enabled the development of organ-specific aging clocks, revealing the distinct aging trajectories and their clinical implications. We used protein-based aging estimators for 11 organs, applying them to...

Highly pathogenic avian influenza H5N1 viruses have recently spread to dairy cattle, with high levels of virus detected in milk from affected animals, raising concern about the risk posed by unpasteurized dairy products consumed by humans. Here we evaluated H5N1 virus persistence in raw-milk cheeses (n = 3 per condition) made with milk acidified to pH 6.6, 5.8 and 5.0 before cheese making and validated our findings in raw-milk cheeses (n = 4) inadvertently produced with naturally contaminated...

Psycho-socio-economic factors (PSEFs) such as income, education, housing, and social support are known to influence health outcomes, yet their relationship with cardiorenal multimorbidity (CRM) remains poorly understood. This study aimed to estimate the prevalence of CRM and examine its associations with PSEFs in a large, nationally representative Canadian sample. We analyzed baseline data from 19,370 participants (mean age: 60 years; 49.8% men) in the Canadian Longitudinal Study on Aging, a...

The active system consolidation theory suggests that information transfer between the hippocampus and cortex during sleep underlies memory consolidation in humans. Neural oscillations during sleep, including the temporal coupling between slow oscillations (SO) and sleep spindles (SP), may play a mechanistic role in memory consolidation. However, differences in analytical approaches and the presence of physiological and behavioral moderators have led to inconsistent conclusions. This...

CONCLUSIONS: The burden of multimorbidity is associated with impaired verbal phonemic fluency in individuals with normal cognition or MCI. Although further studies are required to confirm it, impaired verbal phonemic fluency may be an early sign of cognitive decline in older adults with multimorbidity, with potential implications for prevention strategies.