Metabolism, Genomics, and DNA Repair in the Mouse Aging Liver
Overview
Affiliations
The liver plays a pivotal role in the metabolism of nutrients, drugs, hormones, and metabolic waste products, thereby maintaining body homeostasis. The liver undergoes substantial changes in structure and function within old age. Such changes are associated with significant impairment of many hepatic metabolic and detoxification activities, with implications for systemic aging and age-related disease. It has become clear, using rodent models as biological tools, that genetic instability in the form of gross DNA rearrangements or point mutations accumulate in the liver with age. DNA lesions, such as oxidized bases or persistent breaks, increase with age and correlate well with the presence of senescent hepatocytes. The level of DNA damage and/or mutation can be affected by changes in carcinogen activation, decreased ability to repair DNA, or a combination of these factors. This paper covers some of the DNA repair pathways affecting liver homeostasis with age using rodents as model systems.
Zhao Y, Yuan X, Lin T, Yang Q, Jiang X, Yang S Diabetol Metab Syndr. 2024; 16(1):74.
PMID: 38519973 PMC: 10960482. DOI: 10.1186/s13098-024-01312-0.
Zhang S, Duan J, Du Y, Xie J, Zhang H, Li C Front Cell Dev Biol. 2021; 9:698442.
PMID: 34368149 PMC: 8339557. DOI: 10.3389/fcell.2021.698442.
Mu J, Yang F, Tan F, Zhou X, Pan Y, Long X Front Pharmacol. 2021; 11:600219.
PMID: 33551806 PMC: 7859970. DOI: 10.3389/fphar.2020.600219.
Brazhnik K, Sun S, Alani O, Kinkhabwala M, Wolkoff A, Maslov A Sci Adv. 2020; 6(5):eaax2659.
PMID: 32064334 PMC: 6994209. DOI: 10.1126/sciadv.aax2659.
Hallmarks of Aging in the Liver.
Hunt N, Kang S, Lockwood G, Le Couteur D, Cogger V Comput Struct Biotechnol J. 2019; 17:1151-1161.
PMID: 31462971 PMC: 6709368. DOI: 10.1016/j.csbj.2019.07.021.