Abstract
Aging is a continuous, universal, and irreversible process that determines progressive loss of adaptability. The liver is a critical organ that supports digestion, metabolism, immunity, detoxification, vitamin storage, and hormone signaling. Nevertheless, the relationship between aging and the development of liver diseases remains elusive. In fact, although prolonged fasting in adult rodents and humans delays the onset of the disease and increases longevity, whether prolonged fasting could exert adverse effects in old organisms remains incompletely understood. In this work, we aimed to characterize the oxidative stress and nuclear proteome in the liver of 3-month- and 24-month-old male Wistar rats upon 36 h of fasting and its adaptation in response to 30 min of refeeding. To this end, we analyzed the hepatic lipid peroxidation levels (TBARS) and the expression levels of genes associated with fat metabolism and oxidative stress during aging. In addition, to gain a better insight into the molecular and cellular processes that characterize the liver of old rats, the hepatic nuclear proteome was also evaluated by isobaric tag quantitation (iTRAQ) mass spectrometry-based proteomics. In old rats, aging combined with prolonged fasting had great impact on lipid peroxidation in the liver that was associated with a marked downregulation of antioxidant genes (Sod2, Fmo3, and Cyp2C11) compared to young rats. Besides, our proteomic study revealed that RNA splicing is the hepatic nuclear biological process markedly affected by aging and this modification persists upon refeeding. Our results suggest that aged-induced changes in the nuclear proteome could affect processes associated with the adaptative response to refeeding after prolonged fasting, such as those involved in the defense against oxidative stress.
Highlights
Aging is a natural process involving the whole body
We focused on the liver because the prevalence of chronic liver diseases, such as NAFLD and NAFLD from simple steatosis to steatohepatitis (NASH), is increased in the elderly population
Our findings indicate that proteins that are involved in alternative splicing, spliceosome components, and nucleosome assembly were upregulated in nuclear liver from old compared with young rats, regardless of the prolonged fasting-refeeding cycle, indicating that dysregulation of the splicing process is present in the liver of old rats with
Summary
Aging is a natural process involving the whole body. As a natural process, Gems [1]has suggested that aging is not a disease, even though older people do tend to get ill more often and to develop serious and chronic diseases. Aging is a natural process involving the whole body. Antioxidants 2021, 10, 1535 by a myriad of stress conditions and involve important risk factors for metabolic and physiological disabilities. Many studies in experimental models and humans have been conducted to find the link between oxidative stress and aging at the molecular and cellular levels and revealed that in conditions of metabolic syndrome (MS), oxidative stress could accelerate aging [3]. A considerable amount of evidence points to the process of immunosenescence as the major contributor to the chronic basal inflammation associated with aging (inflammaging) and thereby to increased oxidative stress [4,5]. The biology of aging continues to be poorly understood and whether oxidative stress is a pivotal regulator of aging and age-associated diseases remains conflicting and needs to be resolved
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