Endothelium ‐specific CYP2J2 overexpression attenuates age‐related insulin resistance
In this study, we investigated the effects of endothelium‐specific CYP2J2 overexpression on age‐related insulin resistance and metabolic dysfunction. Endothelium‐specific targeting of the human CYP epoxygenase, CYP2J2, transgenic mice (Tie2‐CYP2J2‐Tr mice) was utilized. The effects of endothelium‐specific CYP2J2 overexpression on aging‐associated obesity, inflammation, and peripheral insulin resistance were evaluated by assessing metabolic parameters in young (3 months old) and aged (16 months old) adult male Tie2‐CYP2J2‐Tr mice. Decreased insulin sensitivity and attenuated insulin signaling in aged ske...
Source: Aging Cell - December 1, 2017 Category: Cytology Authors: Yan Yang, Ruolan Dong, Zhihui Chen, Danli Hu, Menglu Fu, Ying Tang, Dao Wen Wang, Xizhen Xu, Ling Tu Tags: ORIGINAL ARTICLE Source Type: research
The mitochondrial ATP synthase is a shared drug target for aging and dementia
Summary
Aging is a major driving force underlying dementia, such as that caused by Alzheimer's disease (AD). While the idea of targeting aging as a therapeutic strategy is not new, it remains unclear how closely aging and age‐associated diseases are coupled at the molecular level. Here, we discover a novel molecular link between aging and dementia through the identification of the molecular target for the AD drug candidate J147. J147 was developed using a series of phenotypic screening assays mimicking disease toxicities associated with the aging brain. We have previously demonstrated the therapeutic efficacy of J147 in ...
Source: Aging Cell - December 1, 2017 Category: Cytology Authors: Joshua Goldberg, Antonio Currais, Marguerite Prior, Wolfgang Fischer, Chandramouli Chiruta, Eric Ratliff, Daniel Daugherty, Richard Dargusch, Kim Finley, Pau B. Esparza ‐Moltó, José M. Cuezva, Pamela Maher, Michael Petrascheck, David Schubert Tags: ORIGINAL ARTICLE Source Type: research
UNC ‐120/SRF independently controls muscle aging and lifespan in Caenorhabditis elegans
Summary
Aging is commonly defined as the loss of global homeostasis, which results from progressive alteration of all organs function. This model is currently challenged by recent data showing that interventions that extend lifespan do not always increase the overall fitness of the organism. These data suggest the existence of tissue‐specific factors that regulate the pace of aging in a cell‐autonomous manner. Here, we investigated aging of Caenorhabditis elegans striated muscles at the subcellular and the physiological level. Our data show that muscle aging is characterized by a dramatic decrease in the expression of ...
Source: Aging Cell - December 1, 2017 Category: Cytology Authors: Adeline Mergoud dit Lamarche, Laurent Molin, Laura Pierson, Marie ‐Christine Mariol, Jean‐Louis Bessereau, Kathrin Gieseler, Florence Solari Tags: ORIGINAL ARTICLE Source Type: research
Circulating levels of monocyte chemoattractant protein ‐1 as a potential measure of biological age in mice and frailty in humans
Summary
A serum biomarker of biological versus chronological age would have significant impact on clinical care. It could be used to identify individuals at risk of early‐onset frailty or the multimorbidities associated with old age. It may also serve as a surrogate endpoint in clinical trials targeting mechanisms of aging. Here, we identified MCP‐1/CCL2, a chemokine responsible for recruiting monocytes, as a potential biomarker of biological age. Circulating monocyte chemoattractant protein‐1 (MCP‐1) levels increased in an age‐dependent manner in wild‐type (WT) mice. That age‐dependent increase was accelerat...
Source: Aging Cell - December 1, 2017 Category: Cytology Authors: Matthew J. Yousefzadeh, Marissa J. Schafer, Nicole Noren Hooten, Elizabeth J. Atkinson, Michele K. Evans, Darren J. Baker, Ellen K. Quarles, Paul D. Robbins, Warren C. Ladiges, Nathan K. LeBrasseur, Laura J. Niedernhofer Tags: ORIGINAL ARTICLE Source Type: research
Senescence promotes in vivo reprogramming through p16INK4a and IL‐6
We report that Ink4a, but not Arf, is necessary for OSKM‐induced senescence and, thereby, for the paracrine stimulation of reprogramming. However, in the absence of p53, IL6 production and reprogramming become independent of Ink4a, as revealed by the analysis of Ink4a/Arf/p53 deficient mice. In the case of the cell cycle inhibitor p21, its protein levels are highly elevated upon OSKM activation in a p53‐independent manner, and we show that p21‐null tissues present increased levels of senescence, IL6, and reprogramming. We also report that Il6‐mutant tissues are impaired in undergoing reprogramming, thus reinforcing...
Source: Aging Cell - December 1, 2017 Category: Cytology Authors: Lluc Mosteiro, Cristina Pantoja, Alba Martino, Manuel Serrano Tags: ORIGINAL ARTICLE Source Type: research
