de Grey Aubrey D N J
Dept of Genetics, University of Cambridge, UK.
Trends Biotechnol. 2002 Nov;20(11):452-5. doi: 10.1016/s0167-7799(02)02062-0.
Lysosomal degradation of damaged macromolecules is imperfect: many cell types accumulate lysosomal aggregates with age. Some such deposits are known, or are strongly suspected, to cause age-related disorders such as atherosclerosis and neurodegeration. It is possible that they also influence the rate of aging in general. Lysosomal degradation involves extensive cooperation between the participating enzymes: each generates a substrate for others until breakdown of the target material to recyclable units (such as amino acids) is complete. Hence, the age-related accumulation of lysosomal aggregates might be markedly retarded, or even reversed, by introducing just a few bacterial or fungal enzymes -'xenohydrolases' - that can degrade molecules that our natural machinery cannot. This article examines the feasibility and biomedical potential of such lysosomal enhancement as an approach to retarding or treating age-related physiological decline and disease.
许多细胞类型会随着年龄增长积累溶酶体聚集体。已知其中一些沉积物会导致，或极有可能导致，诸如动脉粥样硬化和神经退行性变等与年龄相关的疾病。它们也有可能总体上影响衰老速度。溶酶体降解涉及参与其中的酶之间的广泛协作：每种酶都为其他酶生成底物，直到目标物质分解为可循环利用的单元（如氨基酸）为止。因此，通过引入少数几种能够降解我们自身天然机制无法降解的分子的细菌或真菌酶——“外源水解酶”，溶酶体聚集体与年龄相关的积累可能会显著减缓，甚至逆转。本文探讨了这种溶酶体增强作为延缓或治疗与年龄相关的生理衰退和疾病的一种方法的可行性和生物医学潜力。
