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AMPKα2 signals amino acid insufficiency to inhibit protein synthesis

1 month 2 weeks ago
The functional difference between the two catalytic subunits, α1 and α2, of AMP-activated protein kinase (AMPK) complexes remains elusive. Herein, we report that AMPKα2 specifically transduces amino acid insufficiency signals to protein synthesis. Low amino acid levels, high protein levels, and reduced phosphorylation of AMPKα threonine 172 (p-T172) are observed in blood samples in patients with Alzheimer's disease (AD) from a cohort of 1,000,000 Chinese individuals. Loss of α2, but not α1,...
Yunzi Mao

Extracellular vesicle-based biosensors for Alzheimer's disease: A new frontier in precision diagnostics

1 month 2 weeks ago
Alzheimer's disease (AD), the most prevalent neurodegenerative disorder, remains a diagnostic challenge due to its asymptomatic early stages and the lack of reliable, non-invasive biomarkers. Extracellular vesicles (EVs), including exosomes and microvesicles, are nano-sized membrane-bound particles released by cells into biological fluids and have emerged as promising carriers of disease-specific biomarkers. These vesicles reflect the physiological and pathological state of their parental cells,...
JinJin Pei

Apraxic deficits in Alzheimer's disease are associated with altered dynamic connectivity in praxis-related networks

1 month 2 weeks ago
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...
Taylan D Kuzu

Experimental Evidence Against Taurine Deficiency as a Driver of Aging in Humans

1 month 2 weeks ago
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...
Vincent Marcangeli

Single-cell and spatial detection of senescent cells using DeepScence

1 month 2 weeks ago
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...
Yilong Qu

The secreted metabolite sensor CtBP2 links metabolism to healthy lifespan

1 month 2 weeks ago
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...
Motohiro Sekiya

Fosl2 facilitates chromatin accessibility to determine developmental events during follicular maturation

1 month 2 weeks ago
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...
Hongyong Zhang

Sperm sequencing reveals extensive positive selection in the male germline

1 month 2 weeks ago
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...
Matthew D C Neville

Somatic mutation and selection at population scale

1 month 2 weeks ago
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...
Andrew R J Lawson

Patterns of Organ-Specific Proteomic Aging in Relation to Lifestyle, Diseases, and Mortality

1 month 2 weeks ago
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...
Qi Wang