Page 18 - A. Aging

[A. Aging-10]

Growth differentiation factor 15 regulates aging-mediated

systemic inflammatory response

Hyon-Seung Yi¹

¹Internal Medicine, Chungnam National University School of Medicine, Daejeon 35015, South Korea

Mitochondrial dysfunction is associated with aging-mediated inflammatory responses, leading to metabolic
deterioration, development of insulin resistance, and type 2 diabetes. Growth differentiation factor 15 (GDF15) is an
important mitokine generated in response to mitochondrial stress and dysfunction, however, the implications of

GDF15 to the aging process are poorly understood in mammals. In this study, we identified a link between

mitochondrial stress-induced GDF15 production and protection from tissue inflammation on aging in humans and
mice. We observed an increase in serum levels and hepatic expression of GDF15 as well as pro-inflammatory
cytokines in elderly subjects. In the BXD mouse reference population, mice with metabolic impairments and shorter

survival were found to exhibit higher hepatic Gdf15 expression. Mendelian randomization links reduced GDF15
expression in human blood to increased body weight and inflammation. GDF15 deficiency promotes tissue

inflammation by increasing the activation of resident immune cells in metabolic organs, such as in the liver and
adipose tissues of 20-month-old mice. Taken together, these data reveal that GDF15 is indispensable for attenuating

aging-mediated local and systemic inflammation.