Aging & Longevity

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...

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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.

Phytochemicals represent emerging anti-aging therapeutic candidates, with Marchantia polymorpha L. (liverwort) gaining significant attention due to its broad-spectrum pharmacological properties. This plant exhibits remarkable wound-healing and regenerative capabilities, making it a promising candidate for the development of modern anti-aging drugs. In the presented study, 12-ethoxy-Marchantin A (EMA), a new macrocyclic bis-bibenzyl compound, was isolated and identified from M. polymorpha. Using...

Aging depends on genetic and environmental factors, but the specific cell types and mechanisms that coordinate aging of the entire organism are not yet fully understood. Glial cells regulate ionic homeostasis, which is essential for neuronal function and survival. Here, we investigated the role of glial ion channel CLH-1, which is a glial pH regulator, in aging. We found that loss of clh-1 extends life span, improves stress resistance, reduces neuronal damage, and extends health span. These...

The photochemical conversion of CO(2) into valuable fuels faces challenges of low efficiency and poor selectivity. Hydrated electrons (e(aq)^(-)), with their extremely negative reduction potential, are promising CO(2)-reducing agents, yet their short lifetime limits selectivity and high-energy-density product formation. Herein, we show that microdroplet interfaces with strong electric fields (10⁹ volts per meter) substantially extend the lifespan of e(aq)^(-) generated from industrial sulfite...

CONCLUSION: Prior incarceration is a social determinant of health for older adults, even those with distant incarceration history, and is strongly associated with current poverty and meeting criteria for disability. Further research is needed to understand the mechanisms of these associations and means to mitigate health harms associated with prior incarceration.

As the global trend of population aging intensifies, frailty among the elderly has emerged as a significant public Health concern. This study examines the relationship between physical activity levels and the Frailty Index in older adults, utilizing data from the 2018 China Health and Retirement Longitudinal Study (CHARLS). The study sample included 10,240 Chinese adults aged ≥ 60 years.Frailty was assessed using the Frailty Index (FI), which was calculated based on the accumulation of...

Living organisms are physical-energetic systems that must obey simple principles guiding energy transformation across physical and temporal scales. The energy resistance principle (ERP) describes behavior and transformation of energy in the carbon-based circuitry of biology. We show how energy resistance (éR) is the fundamental property that enables transformation, converting into useful work the unformed energy potential of food-derived electrons fluxing toward oxygen. Although éR is required...

Impaired autophagy and increased cellular senescence in the aging epididymis may lead to cellular stress, inflammation, and epithelial dysfunction. This reduction in autophagy can be identified using light and electron microscopy, as well as molecular biology techniques. Autophagy, which may be selective or non-selective, is tightly regulated by genes such as LC3 and LAMP-2. Decreased autophagic activity in the epididymis results in reduced sperm quality and male fertility. These findings...

Chrysin (5,7-dihydroxyflavone), a natural flavonoid present in honey, propolis, and various medicinal plants, has shown promise as a calorie restriction mimetic (CRM) through its glycolysis-inhibiting action. This inhibition promotes a metabolic shift toward oxidative phosphorylation and fatty acid oxidation, potentially activating beneficial pathways like AMPK and SIRT1. The mechanism likely involves the downregulation of Hexokinase-2, leading to suppressed glycolysis and promotion of...