High dietary protein and fat contents exacerbate hepatic senescence and SASP in mice
Jamil Nehmea b c d, Dengbao Yange f, Abdullah Altuleab d, Marta Varela-Eirínb d, Lu Wangg h, Sumei Hue f i j, Yingga Wue f, Jacques Togoe f, Chaoqun Niue f, John Roger Speakmane f k l✉, Marco Demariab d✉
- aDoctoral School of Science and Technology Lebanese University Hadath, Beirut Lebanon
- bEuropean Research Institute for the Biology of Ageing (ERIBA) University Medical Center Groningen (UMCG) University of Groningen (RUG) The Netherlands
- cDoctoral School of Science and Technology, Lebanese University, Hadath, Beirut, Lebanon
- dEuropean Research Institute for the Biology of Ageing (ERIBA), University Medical Center Groningen (UMCG), University of Groningen (RUG), The Netherlands
- eInstitute of Genetics and Developmental Biology Chinese Academy of Sciences Beijing Technology and Business University China
- fInstitute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing Technology and Business University, China
- gSchool of Pharmacy Yantai University China
- hSchool of Pharmacy, Yantai University, China
- iBeijing Advanced Innovation Center for Food Nutrition and Human Health Beijing Engineering and Technology Research Center of Food Additives National Soybean Processing Industry Technology Innovation Center Beijing Technology and Business University China
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Abstract
Dietary choices have a profound impact on the aging process. In addition to the total amount of energy intake, macronutrient composition influences both health and lifespan. However, the exact mechanisms by which dietary macronutrients influence onset and progression of age-associated features remain poorly understood. Cellular senescence is a state of stable growth arrest characterized by the secretion of numerous bioactive molecules with pro-inflammatory properties. Accumulation of senescent cells is considered one of the basic mechanisms of aging and an important contributor to chronic inflammation and tissue degeneration. Whether dietary macronutrients affect the accumulation and the phenotype of senescent cells with age is still unknown. Here, we show that feeding on diets with varying ratios of dietary macronutrients for 3 months has a significant effect on different senescence-associated markers in the mouse liver. High protein intake is associated with higher expression levels of the two classical senescence-associated growth arrest genes, p21 and p16. Furthermore, the expression of many pro-inflammatory secretory markers was increased in diets enriched in protein and further enhanced by increases in fat content. These results provide preliminary evidence that dietary macronutrients have a significant influence on senescence markers and merit further investigation.