PMID- 36802043 OWN - NLM STAT- MEDLINE DCOM- 20230501 LR - 20230502 IS - 1573-6768 (Electronic) IS - 1389-5729 (Linking) VI - 24 IP - 3 DP - 2023 Jun TI - Early-onset caloric restriction alleviates ageing-associated steatohepatitis in male mice via restoring mitochondrial homeostasis. PG - 391-401 LID - 10.1007/s10522-023-10023-4 [doi] AB - Non-alcoholic fatty liver disease is associated with ageing, and impaired mitochondrial homeostasis is the main cause for hepatic ageing. Caloric restriction (CR) is a promising therapeutic approach for fatty liver. The purpose of the present study was to investigate the possibility of early-onset CR in decelerating the progression of ageing-related steatohepatitis. The putative mechanism associated with mitochondria was further determined. C57BL/6 male mice at 8 weeks of age were randomly assigned to one of three treatments: Young-AL (AL, ad libitum), Aged-AL, or Aged-CR (60% intake of AL). Mice were sacrificed when they were 7 months old (Young) or 20 months old (Aged). Aged-AL mice displayed the greatest body weight, liver weight, and liver relative weight among treatments. Steatosis, lipid peroxidation, inflammation, and fibrosis coexisted in the aged liver. Mega mitochondria with short, randomly organized crista were noticed in the aged liver. The CR ameliorated these unfavourable outcomes. The level of hepatic ATP decreased with ageing, but this was reversed by CR. Ageing caused a decrease in mitochondrial-related protein expressions of respiratory chain complexes (NDUFB8 and SDHB) and fission (DRP1), but an increase in proteins related to mitochondrial biogenesis (TFAM), and fusion (MFN2). CR reversed the expression of these proteins in the aged liver. Both Aged-CR and Young-AL revealed a comparable pattern of protein expression. To summarize, this study demonstrated the potential of early-onset CR in preventing ageing-associated steatohepatitis, and maintaining mitochondrial functions may contribute to CR's protection during hepatic ageing. CI - (c) 2023. The Author(s), under exclusive licence to Springer Nature B.V. FAU - Chiang, Chun-Hsien AU - Chiang CH AD - Department of Animal Science and Technology, National Taiwan University, Taipei, Taiwan. FAU - Li, Sin-Jin AU - Li SJ AD - Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA. FAU - Lin, Yu-Han AU - Lin YH AD - Department of Animal Science and Technology, National Taiwan University, Taipei, Taiwan. FAU - Wang, Pei-Yu AU - Wang PY AD - Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei, Taiwan. FAU - Hsu, Pu-Sheng AU - Hsu PS AD - Institute of Biotechnology, National Taiwan University, Taipei, Taiwan. FAU - Lin, Shau-Ping AU - Lin SP AD - Institute of Biotechnology, National Taiwan University, Taipei, Taiwan. FAU - Chiang, Ting-Chia AU - Chiang TC AD - Department of Animal Science and Technology, National Taiwan University, Taipei, Taiwan. FAU - Chen, Ching-Yi AU - Chen CY AD - Department of Animal Science and Technology, National Taiwan University, Taipei, Taiwan. ronichen@ntu.edu.tw. AD - Department of Animal Science and Technology, National Taiwan University, No. 50, Lane 155, Sec 3, Keelung Rd, Taipei, 10672, Taiwan. ronichen@ntu.edu.tw. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230220 PL - Netherlands TA - Biogerontology JT - Biogerontology JID - 100930043 SB - IM MH - Mice MH - Male MH - Animals MH - *Caloric Restriction MH - Mice, Inbred C57BL MH - Mitochondria MH - *Fatty Liver/prevention & control MH - Aging/metabolism MH - Homeostasis OTO - NOTNLM OT - Ageing OT - Caloric restriction OT - Energy deficit OT - Mitochondrial functions OT - Steatohepatitis EDAT- 2023/02/22 06:00 MHDA- 2023/05/01 06:42 CRDT- 2023/02/21 16:52 PHST- 2022/12/30 00:00 [received] PHST- 2023/02/07 00:00 [accepted] PHST- 2023/05/01 06:42 [medline] PHST- 2023/02/22 06:00 [pubmed] PHST- 2023/02/21 16:52 [entrez] AID - 10.1007/s10522-023-10023-4 [pii] AID - 10.1007/s10522-023-10023-4 [doi] PST - ppublish SO - Biogerontology. 2023 Jun;24(3):391-401. doi: 10.1007/s10522-023-10023-4. Epub 2023 Feb 20.