Structural and functional implications of age-related abnormal modifications in collagen II from intervertebral disc.
Collagen II was isolated from annulus fibrosus of human donors, and the degree of enzymatic glycosylation and the extent of nonenzymatic modification was determined as a function of age. While enzymatic glycosylation did not alter with age, the fluorescence as a measure of nonenzymatic modification increased, in particular in those fractions containing highly cross-linked collagen molecules. The age-dependent increase of fluorescence was associated with a lower thermal stability of collagen II, being lowest (Tm = 36.9 degrees C instead of 42.1 degrees C) in a fraction of collagen II molecules isolated from tissue of a 69-year-old donor. In addition, collagen II from elderly donors showed an impaired propensity to form fibrils, using an in vitro assay, as evidenced by the facts that (1) more collagen molecules remained in solution and were not assembled into fibrils, and (2) the relative turbidity caused by the aggregates progressively decreased as the age of the donors increased. As seen on electron micrographs, these fibrillar aggregates were less densely packed and intermingled with precipitates such as unbanded filaments or discontinuous fibrils with split and frayed regions. It can be hypothesized that functional impairment of the intervertebral disc with aging may be caused in part by molecular alterations as are described here for collagen II obtained from aged donors.
Yang
C
C
Institut für Medizinische Molekularbiologie, Medizinische Universität zu Lübeck, Germany.
Mosler
S
S
Rui
H
H
Baetge
B
B
Notbohm
H
H
Müller
P K
PK
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D002648:Child; D003094:Collagen / Q000737:chemistry* / Q000302:isolation & purification / Q000648:ultrastructure; D017364:Collagenases; D003238:Connective Tissue / Q000648:ultrastructure; D005453:Fluorescence; D006031:Glycosylation; D006358:Hot Temperature; D006801:Humans; D007403:Intervertebral Disc / Q000737:chemistry*; D008854:Microscopy, Electron; D008875:Middle Aged; D014357:Trypsin
D003094:Collagen; D014357:Trypsin; D017364:Collagenases