PPARγ agonists delay age‐associated metabolic disease and extend longevity

• DOI: 10.1111/acel.13267
• Publication Date: 2020-11-21T12:48:11Z
• Authors: Lingyan Xu; Xinran Ma; Narendra Verma; Luce Perie; Jay Pendse; Sama Shamloo; Anne Marie Josephson; Dongmei Wang; Jin Qiu; Mingwei Guo; Xiaodan Ping; Michele Allen; Audrey Noguchi; Danielle Springer; Fei Shen; Caizhi Liu; Shiwei Zhang; Lingyu Li; Jin Li; Junjie Xiao; Jian Lu; Zhenyu Du; Jian Luo; Jose O. Aleman; Philipp Leucht; Elisabetta Mueller
• Keywords: Rosiglitazone; Pioglitazone; Senescence; Glimepiride

Abstract Aging leads to a number of disorders caused by cellular senescence, tissue damage, and organ dysfunction. It has been reported that anti‐inflammatory insulin‐sensitizing compounds delay, or reverse, the aging process prevent metabolic disorders, neurodegenerative disease, muscle atrophy, improving healthspan extending lifespan. Here we investigated effects PPARγ agonists in preventing increasing longevity, given their known properties lowering inflammation decreasing glycemia. Our molecular physiological studies show long‐term treatment mice at 14 months age with low doses ligand rosiglitazone (Rosi) improved glucose metabolism mitochondrial functionality. These were associated decreased reduced cognitive function, diminished anxiety‐ depression‐like conditions, without any adverse on cardiac skeletal Furthermore, Rosi started when they old was lifespan extension. A retrospective analysis agonist pioglitazone (Pio) longevity showed mortality patients receiving Pio compared those PPARγ‐independent insulin secretagogue glimepiride. Taken together, these data suggest possibility using promote healthy extend