Department of Comparative Medicine, School of Medicine, University of Washington, Seattle, WA, USA.
University of Washington Health Sciences Center, I-446 Box 357350, WA, 98195, Seattle, USA.
Geroscience. 2023 Feb;45(1):385-397. doi: 10.1007/s11357-022-00641-0. Epub 2022 Aug 16.
Canagliflozin (Cana), a clinically important anti-diabetes drug, leads to a 14% increase in median lifespan and a 9% increase in the 90th percentile age when given to genetically heterogeneous male mice from 7 months of age, but does not increase lifespan in female mice. A histopathological study was conducted on 22-month-old mice to see if Cana retarded diverse forms of age-dependent pathology. This agent was found to diminish incidence or severity, in male mice only, of cardiomyopathy, glomerulonephropathy, arteriosclerosis, hepatic microvesicular cytoplasmic vacuolation (lipidosis), and adrenal cortical neoplasms. Protection against atrophy of the exocrine pancreas was seen in both males and females. Thus, the extension of lifespan in Cana-treated male mice, which is likely to reflect host- or tumor-mediated delay in lethal neoplasms, is accompanied by parallel retardation of lesions, in multiple tissues, that seldom if ever lead to death in these mice. Canagliflozin thus can be considered a drug that acts to slow the aging process and should be evaluated for potential protective effects against many other late-life conditions.
卡格列净(Cana)是一种临床上重要的抗糖尿病药物,可使遗传异质性雄性小鼠的中位寿命延长 14%,90 百分位数年龄增加 9%,该药物从 7 月龄开始给药,但不会延长雌性小鼠的寿命。对 22 月龄的小鼠进行了一项组织病理学研究,以观察 Cana 是否会延缓各种与年龄相关的病变。结果发现,该药物仅能降低雄性小鼠的心肌病、肾小球肾炎、动脉硬化、肝微泡细胞质空泡变性(脂肪变性)和肾上腺皮质肿瘤的发生率或严重程度。在雄性和雌性小鼠中都观察到对胰腺外分泌组织萎缩的保护作用。因此,在 Cana 治疗的雄性小鼠中寿命延长,这可能反映了宿主或肿瘤介导的致死性肿瘤的延迟,同时也伴有多种组织中病变的平行延迟,这些病变在这些小鼠中很少导致死亡。因此,可以认为卡格列净是一种能够减缓衰老过程的药物,应该评估其对许多其他晚年疾病的潜在保护作用。