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Summary BACE1 (β‐secretase) plays a central role in the β‐amyloidogenesis of Alzheimer’s disease (AD). The ubiquitin–proteasome system, a major intracellular protein quality control system, has been implicated recently in BACE1 metabolism. We report that the SCFFbx2‐E3 ligase is...
Summary To identify new genetic regulators of cellular aging and senescence, we performed genome‐wide comparative RNA profiling with selected human cellular model systems, reflecting replicative senescence, stress‐induced premature senescence, and distinct other forms of cellular aging. Gene...
Summary Conserved metallo β‐Lactamase and β‐CASP (CPSF‐Artemis‐Snm1‐Pso2) domain nuclease family member SNM1B/Apollo is a shelterin‐associated protein that localizes to telomeres through its interaction with TRF2. To study its in vivo role, we generated a knockout of SNM1B/Apollo in...
Summary Genetic variation in FOXO3A has previously been associated with human longevity. Studies published so far have been case–control studies and hence vulnerable to bias introduced by cohort effects. In this study we extended the previous findings in the cohorts of oldest old Danes (the...
Summary The mitochondrial retrograde response has been extensively described in Saccharomyces cerevisiae, where it has been found to extend life span during times of mitochondrial dysfunction, damage or low nutrient levels. In yeast, the retrograde response genes (RTG) convey these stress...
Summary Mutations in the nuclear envelope protein lamin A or in its processing protease ZMPSTE24 cause human accelerated aging syndromes, including Hutchinson–Gilford progeria syndrome. Similarly, Zmpste24‐deficient mice accumulate unprocessed prelamin A and develop multiple progeroid...
Summary Aging decreases the human femur’s fatigue resistance, impact energy absorption, and the ability to withstand load. Changes in the osteocyte distribution and in their elemental composition might be involved in age‐related bone impairment. To address this question, we carried out a...
Summary In muscle, aging is associated with a failure of adaptive responses to contractile activity, and this is hypothesized to play an important role in age‐related loss of muscle mass and function. Mice lacking the Cu,Zn superoxide dismutase (Cu,ZnSOD, SOD1) show an accelerated,...
Summary Neural precursor cell (NPC) transplantation may have a role in restoring brain function after stroke, but how aging might affect the brain’s receptivity to such transplants is unknown. We reported previously that transplantation of human embryonic stem cell (hESC)‐derived NPCs...
Summary Macrophage inhibitory cytokine‐1 (MIC‐1/GDF15) is a member of the TGF‐b superfamily, previously studied in cancer and inflammation. In addition to regulating body weight, MIC‐1/GDF15 may be used to predict mortality and/or disease course in cancer, cardiovascular disease (CVD),...
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