High dietary protein and fat contents exacerbate hepatic senescence and SASP in mice

Jamil Nehme, Dengbao Yang, Abdullah Altulea, Marta Varela-Eirin, Lu Wang, Sumei Hu, Yingga Wu, Jacques Togo, Chaoqun Niu, John R Speakman*, Marco Demaria*

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    11 Citations (Scopus)
    107 Downloads (Pure)

    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.

    Original languageEnglish
    Pages (from-to)1340-1347
    Number of pages8
    JournalThe FEBS Journal
    Volume290
    Issue number5
    Early online date15-Dec-2021
    DOIs
    Publication statusPublished - Mar-2023

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