Effects of a prolonged diet regimen on autophagic function in rat islets with aging

• Published in: Experimental gerontology Vol. 159; p. 111659
• Main Authors: Gu, Zhao-Yan, Miao, Xin-Yu, Cui, Jing, Yang, Fan, Ma, Li-Chao, Li, Chun-Lin, Sun, Ban-Ruo, Yan, Shuang-Tong
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01.03.2022
• Subjects: Aging; Aging - physiology; Animals; Autophagy; Caloric restriction; Diabetes Mellitus, Type 2; Diet, High-Fat - adverse effects; High-fat diet; Islets; Rats; Rats, Inbred F344; Type 2 diabetes; β-cells; Type 2 diabetes; β-cells; High-fat diet; Aging; Islets; Autophagy; Caloric restriction
• ISSN: 0531-5565; 1873-6815; 1873-6815
• DOI: 10.1016/j.exger.2021.111659

The prevalence of type 2 diabetes increases with age-associated increased susceptibility of islet β-cells and altered dietary patterns, in part because of insufficient compensation of β-cell functional mass in the face of increasing insulin resistance. However, the underlying mechanisms have not been fully elucidated. In the present study, we investigated the effects of a long-term calorie-restricted (CR) or high-fat (HF) diet compared to a normal ad libitum diet on β-cell structure–function relationships and autophagy in the islets of 3- and 24-month-old Fischer 344 rats. Aging and the HF diet decreased the β-cell-to-islet area ratio, disorganized the islet structure, and increased the expression of senescence markers. Aging and the long-term HF diet also decreased autophagy-related proteins, which suggests compromised autophagic function. These findings were further corroborated by increased p62 accumulation and polyubiquitin aggregates observed with aging and the HF diet intervention; these are cardinal markers of attenuated autophagic function. It is important to note that the 24-month-old rats maintained on the CR diet closely mimicked the 3-month-old rats, which indicates that a long-term CR diet can delay islet aging and prevent the decline in the autophagic function of islets during the aging process. Taken together, our results indicate an autophagy-dependent mechanism responsible for islet function in older people or those with altered dietary patterns and lay the foundations for future research leading to novel therapeutic strategies for treating diabetes. •Aging and the high-fat (HF) diet decreased the β-cell-to-islet area ratio and increased the expression of senescence markers.•Pancreatic β-cell proliferation increased and apoptosis decreased in the calorie-restricted (CR) diet group compared to the ad libitum (AL) diet group; the rate of apoptosis was significantly higher in the HF group than in the AL group.•Aging and the long-term HF diet compromised autophagic function that causes oxidative stress and mitochondrial damage.•A long-term CR diet can delay islet aging and prevent the decline in the autophagic function of islets during the aging process.