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Direct measurement of the male germline mutation rate in individuals using sequential sperm samples

12 hours 50 minutes ago
Mutations that accumulate in the human male germline with age are a major driver of genetic diversity and contribute to genetic diseases. However, aging-related male germline mutation rates have not been measured directly in germline cells (sperm) at the level of individuals. We developed a study design in which we recalled 23 sperm donors with prior banked samples to provide new sperm samples. The old and new sequential sperm samples were separated by long timespans, ranging from 10 to 33...
Jonathan E Shoag

Ecological restoration in the Yellow River Basin enhances hydropower potential

12 hours 50 minutes ago
Hydropower, an important renewable energy source worldwide, is threatened by reservoir sedimentation. Ecological restoration (ER) can mitigate this by reducing upstream sediment, thereby extending hydropower facilities' lifespan. However, ER may also reduce runoff, potentially diminishing energy generation and complicating its overall impact on hydropower potential. Here, we examine China's Yellow River, once the world's most sediment-laden river, using eco-hydrological and reservoir regulation...
Xutong Wu

Multi-cohort cerebrospinal fluid proteomics identifies robust molecular signatures across the Alzheimer disease continuum

1 day 12 hours ago
Changes in β-amyloid (Aβ) and hyperphosphorylated tau (T) in brain and cerebrospinal fluid (CSF) precede Alzheimer's disease (AD) symptoms, making the CSF proteome a potential avenue to understand disease pathophysiology and facilitate reliable diagnostics and therapies. Using the AT framework and a three-stage study design (discovery, replication, and meta-analysis), we identified 2,173 analytes (2,029 unique proteins) dysregulated in AD. Of these, 865 (43%) were previously reported, and 1,164...
Muhammad Ali

Enteric nervous system dysfunction as a driver of central nervous system disorders: The Forgotten brain in neurological disease

1 day 12 hours ago
The Enteric Nervous System (ENS), often called the "second brain," is a complex network of neurons and glial cells within the gastrointestinal (GI) tract. It functions autonomously while maintaining close communication with the central nervous system (CNS) via the gut-brain axis (GBA). ENS dysfunction plays a crucial role in neurodegenerative and neurodevelopmental disorders, including Parkinson's disease, Alzheimer's disease, and autism spectrum disorder. Disruptions such as altered...
Orabi Hajjeh

Endothelial TDP-43 depletion disrupts core blood-brain barrier pathways in neurodegeneration

1 day 12 hours ago
Endothelial cells (ECs) help maintain the blood-brain barrier but deteriorate in many neurodegenerative disorders. Here we show, using a specialized method to isolate EC and microglial nuclei from postmortem human cortex (92 donors, 50 male and 42 female, aged 20-98 years), that intranuclear cellular indexing of transcriptomes and epitopes enables simultaneous profiling of nuclear proteins and RNA transcripts at a single-nucleus resolution. We identify a disease-associated subset of capillary...
Omar M F Omar

Aging modulates large-scale neural network interactions during speech comprehension

1 day 12 hours ago
Speech comprehension in noisy environments constitutes a critical challenge in everyday life and affects people of all ages. This challenging listening situation can be alleviated using semantic context to predict upcoming words (i.e., predictability gain)-a process associated with the domain-specific semantic network. When no such context can be used, speech comprehension in challenging listening conditions relies on cognitive control functions, underpinned by domain-general networks. Most...
Anna Uta Rysop

Multi-cohort cerebrospinal fluid proteomics identifies robust molecular signatures across the Alzheimer disease continuum

1 day 12 hours ago
Changes in β-amyloid (Aβ) and hyperphosphorylated tau (T) in brain and cerebrospinal fluid (CSF) precede Alzheimer's disease (AD) symptoms, making the CSF proteome a potential avenue to understand disease pathophysiology and facilitate reliable diagnostics and therapies. Using the AT framework and a three-stage study design (discovery, replication, and meta-analysis), we identified 2,173 analytes (2,029 unique proteins) dysregulated in AD. Of these, 865 (43%) were previously reported, and 1,164...
Muhammad Ali

Proteomic and phosphoproteomic signatures of aging mouse liver

1 day 12 hours ago
The liver is a metabolic powerhouse, crucial for regulating carbohydrates, fats, and protein metabolism. In this study, we conducted a comparative proteomic and phosphoproteomic analysis of aging mouse livers from young adults (3-4 months) and old (19-21 months) mice to identify age-related changes in liver proteins and phosphosites, which were linked to various metabolic pathways. In old mice, proteins associated with the "complement and coagulation cascade," "age-rage signaling in diabetic...
Rodrigo Mohallem

Telomere length in offspring is determined by mitochondrial-nuclear communication at fertilization

1 day 12 hours ago
The initial setting of telomere length during early life in each individual has a major influence on lifetime risk of aging-associated diseases; however there is limited knowledge of biological signals that regulate inheritance of telomere length, and whether it is modifiable is not known. We now show that when mitochondrial activity is disrupted in mouse zygotes, via exposure to 20% O(2) or rotenone, telomere elongation between the 8-cell and blastocyst stage is impaired, with shorter telomeres...
Yasmyn E Winstanley

SIRT5 safeguards against primate skeletal muscle ageing via desuccinylation of TBK1

1 day 12 hours ago
Ageing-induced skeletal muscle deterioration contributes to sarcopenia and frailty, adversely impacting the quality of life in the elderly. However, the molecular mechanisms behind primate skeletal muscle ageing remain largely unexplored. Here, we show that SIRT5 expression is reduced in aged primate skeletal muscles from both genders. SIRT5 deficiency in human myotubes hastens cellular senescence and intensifies inflammation. Mechanistically, we demonstrate that TBK1 is a natural substrate for...
Qian Zhao

Social disadvantage accelerates aging

1 day 12 hours ago
Social disadvantage, like advanced age, is a risk factor for a broad range of health conditions; however, whether it influences the aging process remains unclear. Here, using a multicohort approach, we investigated the associations of social disadvantage with age-related plasma proteins and age-related diseases. We found proteomic signatures of accelerated immune aging and 14 specific age-related proteins linked to social disadvantage during both early and later life. Individuals experiencing...
Mika Kivimäki

Associated factors of frailty among community-dwelling older adults with multimorbidity from a health ecological perspective: a cross-sectional study

1 day 12 hours ago
CONCLUSIONS: The prevalence of frailty among older adults with comorbidities is exceptionally high, influenced by various dimensions from health ecology perspective. Psychological care and daily behavior management should be strengthened for the frail older with multimorbidity. Precise and individualized care interventions need to be developed to help promote healthy aging.
Yunqiu Che

Salutary effects of transdermal curcumin on multiple indices of health span in rodent models of normal aging and hypertension

1 day 12 hours ago
Geroscience has helped to usher in a new and exciting era of aging drug development and evaluation of novel and repurposed agents, as well as natural compounds purported to target one or more aging hallmarks. Among the latter, curcumin has long been pursued as a promising strategy but has failed to provide convincing evidence in human trials. Oral intake is the typical route of administration tested for the vast majority of gerotherapeutic candidates, including curcumin, but efficacy is...
Kai Mao