Data for Early onset-caloric restriction protectes aging-associated steatohepatitis via restoring mitochondrial homeostasis

Published: 1 February 2023| Version 3 | DOI: 10.17632/d67cdc3c85.3
Ching-Yi Chen,
, Sin-Jin Li, Yu-Han Lin, Pei-Yu Wang, Pu-Sheng Hsu, Shau-Ping Lin, Ting-Chia Chiang


Biological data for early onset caloric restriction on aging associated steatohepatitis Background: Non-alcoholic fatty liver disease is associated with aging, and impaired mitochondrial homeostasis is the main cause for hepatic aging. Caloric restriction (CR) is a promising therapeutic approach to reduce fatty liver. The present study aimed to investigate the effect of early onset CR on decelerating the progression of aging-related steatohepatitis. The potential mechanisms regarding to mitochondria were further evaluated. Methods: Eight-week-old C57BL/6 male mice (n=21) were randomly divided into three groups, Young-AL (AL, ad libitum), Aged-AL, and Aged-CR (60% intake of AL). Mice were sacrificed at the age of 7 months (Young) or 20 months (Aged). Results: Aged-AL mice displayed the greatest body weight, liver weight and liver relative weight among treatments. Aging caused a great grade of steatosis, oxidative stress, inflammation, and fibrosis in the liver. Mega mitochondria with short, randomly organized crista were noticed in the aged liver. CR ameliorated these negative phenomena in aged liver. Aging was accompanied with a lower level of hepatic ATP, while CR restored it. Mitochondrial-related protein expressions of fission and autophagy were suppressed in aged liver. Proteins related to mitochondrial biogenesis, fusion, and mitophagy were upregulated in aged liver. Aged-CR exhibited a similar expression in TFAM, DRP1 and MFN2 as Young-AL did. Major conclusion: early onset CR significantly reversed the negative effect of aging-associated steatohepatitis, including oxidative stress, inflammation, steatosis and fibrosis. Moreover, CR eased aging-associated energy deficit in liver partially via maintaining mitochondrial homeostasis.



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