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Upregulation of ISG15 induced by MAPT/tau accumulation represses autophagic flux by inhibiting HDAC6 activity: a vicious cycle in alzheimer disease
Alzheimer disease (AD), a prevalent neurodegenerative condition in the elderly, is marked by a deficit in macroautophagy/autophagy, leading to intracellular MAPT/tau accumulation. While ISG15 (ISG15 ubiquitin like modifier) has been identified as a regulator of selective autophagy in ataxia telangiectasia (A-T), its role in AD remains unexplored. Our study reveals elevated ISG15 levels in the brains of patients with sporadic AD and AD models in vivo and in vitro. ISG15 overexpression in cells...
A novel monomeric amyloid β-activated signaling pathway regulates brain development via inhibition of microglia
Amyloid β (Aβ) forms aggregates in the Alzheimer's disease brain and is well known for its pathological roles. Recent studies show that it also regulates neuronal physiology in the healthy brain. Whether Aβ also regulates glial physiology in the normal brain, however, has remained unclear. In this article, we describe the discovery of a novel signaling pathway activated by the monomeric form of Aβ in vitro that plays essential roles in the regulation of microglial activity and the assembly of...
Accelerated biological aging, healthy behaviors, and genetic susceptibility with incidence of stroke and its subtypes: A prospective cohort study
Stroke risk increases with chronological age, but the relationship with biological age (BA) acceleration is poorly understood. We aimed to examine the association between BA acceleration and incident stroke and its subtypes, explore the modifying effects on genetic susceptibility, and assess how BA acceleration mediates the effect of behavior score. We studied 253,932 UK Biobank participants and computed two BA measures (Klemera-Doubal Method [KDM], Phenotypic Age [PhenoAge]), with BA...
Ageing limits stemness and tumorigenesis by reprogramming iron homeostasis
Ageing is associated with a decline in the number and fitness of adult stem cells^(1,2). Ageing-associated loss of stemness is posited to suppress tumorigenesis^(3,4), but this hypothesis has not been tested in vivo. Here we use physiologically aged autochthonous genetically engineered^(5,6) mouse models and primary cells^(5,6) to demonstrate that ageing suppresses lung cancer initiation and progression by degrading the stemness of the alveolar cell of origin. This phenotype is underpinned by...
Nicotinamide mononucleotide suppresses cellular senescence and increases aquaporin 5 expression in the submandibular gland of aged male mice to ameliorate aging-related dry mouth
Dry mouth results from decreased saliva secretion due to aging or drug side effects. Decreased saliva secretion causes dryness in the oral cavity that makes swallowing difficult and increases the risk of aspiration pneumonia. There are few fundamental treatments for dry mouth. Here we investigated whether treatment of old mice with nicotinamide mononucleotide (NMN) improved factors associated with dry mouth. Young (16-week-old) and old (113-week-old) male mice were treated subcutaneously with...
Ageing of stem cells reduces their capacity to form tumours
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Daily briefing: What is ageing? Even gerontologists don't agree
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Why breast cancer treatments might work best just after your period
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Study on the age-period-cohort effects of cognitive abilities among older Chinese adults based on the cognitive reserve hypothesis
CONCLUSIONS: The cognitive reserve hypothesis supports the significance of the majority of identified influencing factors. Cognitive abilities demonstrate an accelerating decline with increasing age, following an evolutionary trajectory consistent with physiological principles among older Chinese adults. Since 2008, cognitive abilities have shown a monotonic increasing trend annually, further validating the Flynn effect in this population. The cognitive abilities of the six earlier-born cohorts...
Daily briefing: Stress-induced joylessness leaves a distinct mark on the brain
Age-related changes in mammary gland increase tumorigenesis
Erratum for the Research Article “How do social media feed algorithms affect attitudes and behavior in an election campaign?” by A. M. Guess et al.
Science, Volume 386, Issue 6726, December 2024.
Erratum for the Research Article “APOBEC3 deaminase editing in mpox virus as evidence for sustained human transmission since at least 2016” by Á. O’Toole et al.
Science, Volume 386, Issue 6726, December 2024.
Microbiome interventions for children raise the ethical stakes
What if everyone had masked up? Analysis of app data has an answer
Has Venus ever had an ocean? Its volcanoes hint at an answer
Pregnancy restructures the brain to prepare for childbirth and parenthood
Editorial Expression of Concern
Science, Volume 386, Issue 6726, Page 1102-1102, December 2024.
Editorial Expression of Concern
Science, Volume 386, Issue 6726, Page 1102-1102, December 2024.
In Science Journals
Science, Volume 386, Issue 6726, Page 1104-1106, December 2024.