Martínez de Toda Irene, Rattan Suresh I S, De la Fuente Mónica, Arranz Lorena
Department of Genetics, Physiology and Microbiology (Unit of Animal Physiology), Faculty of Biology, Complutense University, 28040 Madrid, Spain.
Institute of Investigation Hospital 12 Octubre, 28041 Madrid, Spain.
Antioxidants (Basel). 2021 Aug 31;10(9):1397. doi: 10.3390/antiox10091397.
Oxidized, damaged and misfolded proteins accumulate during aging and contribute to impaired cell function and tissue homeodynamics. Damaged proteins are degraded by cellular clearance mechanisms like the 20S proteasome. Aging relates to low 20S proteasome function, whereas long-lived species show high levels. However, contradictory results exist depending on the tissue or cell type and it is unknown how the 20S proteasome functions in exceptionally old mice. The aim of this study was to investigate two proteasome activities (caspase-like and chymotrypsin-like) in several tissues (lung, heart, axillary lymph nodes, liver, kidney) and cells (peritoneal leukocytes) from adult (28 ± 4 weeks, = 12), old (76 ± 4 weeks, = 9) and exceptionally old (128 ± 4 weeks, = 9) BALB/c female mice. The results show different age-related changes depending on the tissue and the activity considered, so there is no universal decline in proteasome function with age in female mice. Interestingly, exceptionally old mice displayed better maintained proteasome activities, suggesting that preserved 20S proteasome is associated with successful aging.
在衰老过程中,氧化、受损和错误折叠的蛋白质会积累,并导致细胞功能受损和组织内环境稳定失调。受损蛋白质通过细胞清除机制(如20S蛋白酶体)进行降解。衰老与20S蛋白酶体功能低下有关,而长寿物种则表现出较高水平。然而,根据组织或细胞类型的不同,存在相互矛盾的结果,并且20S蛋白酶体在特别老龄的小鼠中如何发挥作用尚不清楚。本研究的目的是调查成年(28±4周,n = 12)、老龄(76±4周,n = 9)和特别老龄(128±4周,n = 9)BALB/c雌性小鼠的几种组织(肺、心脏、腋窝淋巴结、肝脏、肾脏)和细胞(腹腔白细胞)中的两种蛋白酶体活性(半胱天冬酶样和胰凝乳蛋白酶样)。结果表明,根据所考虑的组织和活性不同,与年龄相关的变化也不同,因此雌性小鼠的蛋白酶体功能不会随着年龄的增长而普遍下降。有趣的是,特别老龄的小鼠表现出更好维持的蛋白酶体活性,这表明保留的20S蛋白酶体与成功衰老有关。