Age-related Changes in Lung Collagen Metabolism: A Role for Degradation in Regulating Lung Collagen Production

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Abstract
Lung collagen levels are determined by a balance between synthesis and degradation, processes known to have rapid rates in young animals. Here, we report age-related changes in lung collagen synthesis and degradation in rats at five ages from 1 month to 2 yr. Synthesis rates were determined after injection of [14C]proline with a flooding dose of unlabeled proline, and its appearance as hydroxy-[14C]proline in protein. To determine degradation of newly synthesized collagen, the appearance of hydroxy-[14C]proline, either free or in low-molecular-weight peptides, was compared with hydroxy-[14]proline in protein. Fractional collagen synthesis rates decreased from 13.51 ± 0.54%/day at 1 month to 0.97 ± 0.14%/day at 2 yr of age (p < 0.05). Total lung collagen production also fell, but only after 15 months, when it decreased from 2.01 ± 0.16 mg/day at 15 months to 0.54 ± 0.10 mg/day at 2 yr of age (p < 0.05). Fractional rates of total collagen degradation, calculated from the difference between rates of synthesis and rates of collagen deposition, decreased 20-fold from 1 month to 2 yr of age. The proportion of newly synthesized collagen degraded increased from 27.6 ± 3.2% at 1 month to a maximum of 82.3 ± 1.1% at 15 months. These results suggest that lung collagen synthesis and degradation occur throughout life, and that degradative pathways may play important roles in regulating collagen production during growth and ageing.