Shandong Provincial Key Laboratory of Animal Resistant Biology, School of Life Sciences, Shandong Normal University, Jinan, China.
J Gerontol A Biol Sci Med Sci. 2020 Oct 15;75(11):2042-2050. doi: 10.1093/gerona/glaa109.
Metformin, an oral antidiabetic drug, prolongs the life span in nematode, silkworm, and other transgenic rodents, but its effects on longevity and aging-related cognitive ability using natural aging vertebrate models remain poorly understood. The genus of annual fish Nothobranchius show accelerated growth and expression of aging biomarkers. Here, using the short-lived fish Nothobranchius guentheri, we investigated effects of metformin on life span and aging-related cognitive ability and inflammation. Total of 145 fish, 72 fish were fed with metformin in the concentration of 2 mg/g food and 73 fish without metformin from 16 weeks of age until the end of their lives. The chronic feeding with metformin prolonged the life span of the fish and delayed aging with retarded accumulation of lipofuscin in liver, senescence-associated beta-galactosidase (SA-β-gal) activity in skin and serum levels of cholesterol and triglyceride significantly in the 10-month-old fish. Furthermore, metformin improved motor, learning, and memory skills by behavior tests accompanying with reduction of SA-β-gal activity and neurofibrillary degeneration and inhibition of inflammatory response including downregulated NF-κB and proinflammatory cytokines IL-8, TNF-α, and IL-1β expression and enhanced anti-inflammatory cytokine IL-10 level in brain. These findings demonstrate that metformin prolongs the life span and exerts neuroprotective and anti-inflammation function to improve cognitive ability in annual fish. It might be an effective strategy by using metformin to raise the possibility of promoting healthy aging of old population in aging process.
二甲双胍是一种口服降糖药，能延长线虫、家蚕和其他转基因啮齿动物的寿命，但它对使用自然衰老的脊椎动物模型的寿命和与衰老相关的认知能力的影响仍知之甚少。丰年鱼属鱼类表现出加速生长和衰老生物标志物的表达。在这里，我们使用短寿命的鱼类非洲鲫鱼，研究了二甲双胍对寿命和与衰老相关的认知能力和炎症的影响。总共 145 条鱼，72 条鱼用浓度为 2mg/g 食物的二甲双胍喂养，73 条鱼不用二甲双胍从 16 周龄开始直到它们生命结束。慢性喂养二甲双胍延长了鱼类的寿命，并通过延缓肝脏脂褐素的积累、皮肤衰老相关的β-半乳糖苷酶（SA-β-gal）活性以及血清胆固醇和甘油三酯水平的降低来延缓衰老，在 10 个月大的鱼中显著延缓衰老。此外，二甲双胍通过行为测试改善了运动、学习和记忆能力，同时降低了 SA-β-gal 活性和神经纤维原变性，并抑制了炎症反应，包括降低 NF-κB 和促炎细胞因子 IL-8、TNF-α 和 IL-1β的表达以及增强抗炎细胞因子 IL-10 的水平在大脑中。这些发现表明，二甲双胍能延长寿命，发挥神经保护和抗炎功能，提高鱼类的认知能力。在衰老过程中，使用二甲双胍可能是一种有效的策略，可以提高老年人口健康衰老的可能性。
