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Age-dependent impairment of cardiac function and physical performance in male mice with diet-induced obesity
Aging in the context of obesity exacerbates the risk of morbidity and mortality related to cardiovascular disease. However, the maladaptive responses in the heart that arise from prolonged obesity and the specific influence of biological age remain somewhat elusive. This study investigated the effects of diet-induced obesity (DIO) and aging on physical performance and cardiovascular function in mice. 22- and 76-week-old male C57BL/6J mice were randomized to 8 weeks of chow or high-fat diet. Body...
Kynurenine pathway dysregulation via loss of QPRT drives declines in activity and altered metabolism in mice
Chronic inflammatory pathway activation increases with age and is epidemiologically linked to multiple aging-related pathophysiological processes, phenotypes such as physical frailty and sarcopenia and early healthspan declines in aging organisms. Despite this, molecular mechanisms that directly connect chronic inflammation to these conditions remain poorly characterized. We hypothesize that chronic inflammation contributes to the development of age-related phenotypes by increasing the...
A noncanonical cGAS-STING pathway drives cellular and organismal aging
Accumulation of cytosolic DNA has emerged as a hallmark of aging, inducing sterile inflammation. Stimulator of interferon genes (STING) protein translates the sensing of cytosolic DNA by cyclic-GMP-AMP synthase (cGAS) into an inflammatory response. However, the molecular mechanisms whereby cytosolic DNA-induced cGAS-STING pathway leads to aging remain poorly understood. We show that STING does not follow the canonical pathway of activation in human fibroblasts passaged (aging) in culture,...
Modeling heterogeneity in cognitive trajectories in the Framingham Heart Study
INTRODUCTION: The prevalence of cognitive impairment in the population is growing; however, there is substantial heterogeneity in the rate of decline across different cognitive domains. Harmonized factor scores measuring memory, executive function, and language domains have been created in the Framingham Heart Study (FHS).
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Science, Volume 389, Issue 6756, July 2025.
Glymphatic dysfunction in Alzheimer’s disease: A critical appraisal
Science, Volume 389, Issue 6756, July 2025.
Tissue-integrated bionic knee restores versatile legged movement after amputation
Science, Volume 389, Issue 6756, July 2025.
Cryo-EM structure of human telomerase dimer reveals H/ACA RNP-mediated dimerization
Science, Volume 389, Issue 6756, July 2025.
Microglia replacement halts the progression of microgliopathy in mice and humans
Science, Volume 389, Issue 6756, July 2025.
A single theory for the evolution of sex chromosomes and the two rules of speciation
Science, Volume 389, Issue 6756, July 2025.
Human neuron subtype programming via single-cell transcriptome-coupled patterning screens
Science, Volume 389, Issue 6756, July 2025.