Technological Educational Institute of Thessaloniki, Thessaloniki, Greece.
Orentreich Foundation for the Advancement of Science, Inc., Cold Spring-on-Hudson, NY, 10516, USA.
Geroscience. 2020 Feb;42(1):287-297. doi: 10.1007/s11357-019-00129-4. Epub 2019 Nov 14.
Dietary methionine restriction (MR) has been found to enhance longevity across many species. We hypothesized that MR might enhance longevity in part by delaying or inhibiting age-related disease processes. To this end, male Fischer 344 rats were fed control (CF, 0.86% methionine) or MR (0.17% methionine) diets throughout their life until sacrifice at approximately 30 months of age, and histopathology was performed to identify the incidence and progression of two important aging-related pathologies, namely, chronic progressive nephropathy (CPN) and testicular tumorigenesis. Although kidney pathology was observed in 87% CF rats and CPN in 62% of CF animals, no evidence of kidney disease was observed in MR rats. Consistent with the absence of renal pathology, urinary albumin levels were lower in the MR group compared to controls throughout the study, with over a six-fold difference between the groups at 30 months of age. Biomarkers associated with renal disease, namely, clusterin, cystatin C, and β-2 microglobulin, were reduced following 18 months of MR. A reduction in testicular tumor incidence from 88% in CF to 22% in MR rats was also observed. These results suggest that MR may lead to metabolic and cellular changes providing protection against age-related diseases.
限制饮食中的蛋氨酸(MR)已被发现能延长许多物种的寿命。我们假设 MR 可能通过延缓或抑制与年龄相关的疾病进程来延长寿命。为此,雄性 Fischer 344 大鼠在其一生中一直食用对照(CF,0.86%蛋氨酸)或 MR(0.17%蛋氨酸)饮食,直到大约 30 个月大时被处死,并进行组织病理学检查以确定两种重要的与衰老相关的病理学的发生率和进展,即慢性进行性肾病(CPN)和睾丸肿瘤发生。尽管在 87%的 CF 大鼠中观察到肾脏病理学,在 62%的 CF 动物中观察到 CPN,但在 MR 大鼠中未观察到肾脏疾病的证据。与肾脏病理学的缺失一致,MR 组的尿白蛋白水平在整个研究过程中均低于对照组,在 30 个月时两组之间的差异超过六倍。与肾脏疾病相关的生物标志物,即簇蛋白、胱抑素 C 和β-2 微球蛋白,在 MR 18 个月后减少。还观察到 CF 大鼠的睾丸肿瘤发生率从 88%降至 MR 大鼠的 22%。这些结果表明,MR 可能导致代谢和细胞变化,从而提供对与年龄相关疾病的保护。