Hypothalamic gene transfer of BDNF promotes healthy aging in mice

• DOI: 10.1111/acel.12846
• Publication Date: 2018-12-26T09:36:32Z
• Authors: Travis McMurphy; Wei Huang; Xianglan Liu; Jason J. Siu; Nicholas J. Queen; Run Xiao; Lei Cao
• Keywords: Healthy Aging; Mice, Inbred C57BL; 0301 basic medicine; Mice; 03 medical and health sciences; Brain-Derived Neurotrophic Factor; Hypothalamus; Animals; Female; Original Papers; 3. Good health

Abstract The aging process and age‐related diseases all involve perturbed energy adaption impaired ability to cope with adversity. Brain‐derived neurotrophic factor (BDNF) in the hypothalamus plays important role regulation of balance. Our previous studies show that recombinant adeno‐associated virus (AAV)‐mediated hypothalamic BDNF gene transfer alleviates obesity, diabetes, metabolic syndromes both diet‐induced genetic models. Here we examined efficacy safety a built‐in autoregulatory system control transgene expression mimicking body's natural feedback systems middle‐aged mice. Twelve‐month‐old mice were treated either vector or yellow fluorescence protein (YFP) control, maintained on normal diet, monitored for 28 weeks. prevented development aging‐associated declines characterized by: preventing weight gain, reducing adiposity, reversing decline brown fat activity, increasing adiponectin while leptin insulin circulation, improving glucose tolerance, expenditure, alleviating hepatic steatosis, suppressing inflammatory genes adipose tissues. Moreover, treatment reduced anxiety‐like depression‐like behaviors. These data provide evidence is target promoting healthy aging.