Reiser K M, Hennessy S M, Last J A
Department of Internal Medicine, School of Medicine, University of California, Davis 95616.
Biochim Biophys Acta. 1987 Dec 7;926(3):339-48. doi: 10.1016/0304-4165(87)90220-0.
The present study was designed to address a specific question: can we define collagen aging in vivo in terms of alterations in collagen crosslinking? In order to assess the complete spectrum of change throughout life, tissues from rats, monkeys and (where available) humans were examined at ages ranging from fetal to old. Skin and lung were selected in order to include all of the crosslinks derived from lysyl oxidase-generated aldehydes that have been identified thus far, both reducible and nonreducible. Crosslinks analyzed included hydroxylysinonorleucine, dihydroxylysinorleucine, histidinohydroxymerodesmosine, hydroxypyridinium, lysyl pyridinium, and a deoxy analogue of hydroxypyridinium found in skin that differs structurally from lysyl pyridinium. Tissues from both a short-lived species (rats) and a long-lived species (monkeys) were analyzed to test further the hypothesis that changes in crosslinking are linked predominantly to biological age of the animal, rather than temporal aging. We found that biological aging seems to regulate certain predictable changes during the first part of the lifespan: the disappearance postnatally of dihydroxylysinonorleucine in skin, the rapid decrease in difunctional crosslink content in lung and skin during early growth and development, and the gradual rise in hydroxypyridinium and lysyl pyridinium in lung tissue. Changes in crosslinking were far less predictable during the second half of the lifespan. Although hydroxypridinium content continued to rise or reached a plateau in rat and monkey lungs, respectively, it showed a decrease in human lungs. The analogous trifunctional crosslink in skin, the so-called 'pyridinoline analogue', decreased dramatically in both rats and monkeys in later life. Our data suggest that caution must be taken in drawing inferences about human connective tissue aging from experiments performed in short-lived species such as rodents. Furthermore, the finding that there may be fewer total lysyl oxidase-derived crosslinks per collagen molecule in very old animals as compared with young animals suggests that we may need to expand our concepts of collagen crosslinking.
我们能否根据胶原蛋白交联的改变来在体内定义胶原蛋白老化？为了评估整个生命周期内的完整变化范围，对大鼠、猴子以及（如有可用样本）人类从胎儿期到老年期各年龄段的组织进行了检查。选择皮肤和肺组织是为了涵盖迄今为止已鉴定出的所有源自赖氨酰氧化酶生成醛类的交联，包括可还原和不可还原的交联。分析的交联包括羟赖氨酸正亮氨酸、二羟赖氨酸正亮氨酸、组氨酸羟化不完全桥粒、羟基吡啶鎓、赖氨酰吡啶鎓，以及在皮肤中发现的一种羟基吡啶鎓的脱氧类似物，其结构与赖氨酰吡啶鎓不同。对短命物种（大鼠）和长寿物种（猴子）的组织进行分析，以进一步检验交联变化主要与动物的生物学年龄相关而非时间老化这一假设。我们发现，生物学老化似乎在生命周期的第一阶段调节某些可预测的变化：皮肤中二羟赖氨酸正亮氨酸在出生后的消失、肺和皮肤在早期生长发育过程中双功能交联含量的快速下降，以及肺组织中羟基吡啶鎓和赖氨酰吡啶鎓的逐渐升高。在生命周期的后半段，交联的变化则远不可预测。尽管羟基吡啶鎓含量在大鼠和猴子的肺中分别继续上升或达到平台期，但在人类肺中却呈下降趋势。皮肤中类似的三功能交联，即所谓的“吡啶啉类似物”，在大鼠和猴子的后期生活中均显著下降。我们的数据表明，从啮齿动物等短命物种进行的实验中推断人类结缔组织老化时必须谨慎。此外，与年轻动物相比，非常年老的动物每个胶原蛋白分子中源自赖氨酰氧化酶的交联总数可能更少，这一发现表明我们可能需要扩展对胶原蛋白交联的概念。
