Compliance issues across all age groups also remain a paramount hurdle due to calorie restriction adversely affecting mood, thermoregulation, and musculoskeletal mass ( Dirks and Leeuwenburgh, 2006). Although it is well established that dietary interventions, including calorie restriction, can reverse obesity-related metabolic sequelae, many of these strategies are not well tolerated in older patients due to concomitant comorbidities ( Villareal et al., 2005 Jensen et al., 2014). These observations have led many to postulate that obesity may represent a mild progeria syndrome ( Salvestrini et al., 2019 Tzanetakou et al., 2012 Pérez et al., 2016 Tchkonia et al., 2010 Stout et al., 2017a).
Moreover, obesity in mid-life has been shown to accelerate aging mechanisms and induce phenotypes more commonly observed in older mammals ( Bischof and Park, 2015 Horvath et al., 2014 Nevalainen et al., 2017 Yang et al., 2009 Whitmer et al., 2005a Whitmer et al., 2005b Dye et al., 2017). Metabolic detriments associated with advancing age are further exacerbated by obesity ( Villareal et al., 2005 Waters et al., 2013), which has risen substantially in the older population (>65 years) over the past several decades ( Flegal et al., 2010 Flegal et al., 2016). IntroductionĪging is the leading risk factor for most chronic diseases, many of which are associated with declines in metabolic homeostasis ( López-Otín et al., 2013). Collectively, these studies suggest ERα may be a drug target for mitigating chronic diseases in male mammals. Lastly, we also determined that 17α-E2 improves metabolic parameters in male rats, thereby proving that the beneficial effects of 17α-E2 are not limited to mice. Our findings suggest that 17α-E2 may act through the liver and hypothalamus to improve metabolic parameters in male mice. In addition, we show that the ablation of ERα completely attenuates the beneficial metabolic effects of 17α-E2 in male mice. Herein, we show that 17α-estradiol elicits similar genomic binding and transcriptional activation through estrogen receptor α (ERα) to that of 17β-estradiol. The mechanisms by which 17α-estradiol elicits these benefits remain unresolved. 17α-estradiol treatment improves metabolic parameters and slows aging in male mice. Dietary interventions can reverse metabolic declines and slow aging, although compliance issues remain paramount. Metabolic dysfunction underlies several chronic diseases, many of which are exacerbated by obesity. Oklahoma City Veterans Affairs Medical Center, United States.Genes & Human Disease Research Program, Oklahoma Medical Research Foundation, United States.Department of Molecular Pharmacology, Albert Einstein College of Medicine, United States.Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, United States.Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, United States.Department of Cell Biology, University of Oklahoma Health Sciences Center, United States.Department of Biochemistry and Molecular Biology, Mayo Clinic, United States.The Jackson Laboratory, United States.Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, United States.Oklahoma Center for Geroscience, University of Oklahoma Health Sciences Center, United States.Department of Nutritional Sciences, University of Oklahoma Health Sciences Center, United States.
0 kommentar(er)
