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Lung Biology Laboratory, Departments of 1 Pediatrics and 2 Medicine, Georgetown University School of Medicine, Washington, DC 20007-2197
Mammalian alveoli, complex architectural
and cellular units with dimensions that are linked to the organism's
O2 consumption (
O2), are
thought to be destroyed only by disease and not to spontaneously
regenerate. Calorie restriction of adult mammals lowers
O2, and ad libitum refeeding returns
O2 to pre-calorie-restriction values. We
took advantage of these relationships and tested the hypothesis in
adult mice that calorie restriction (two-thirds reduction for 2 wk)
followed by ad libitum refeeding (3 wk) would cause alveolar
destruction and regeneration, respectively. Calorie restriction
diminished alveolar number 55% and alveolar surface area 25%.
Refeeding fully reversed these changes. Neither manipulation altered
lung volume. Within 72 h, calorie restriction increased alveolar
wall cell apoptosis and diminished lung DNA (~20%). By 72 h of refeeding, alveolar wall cell replication increased and lung DNA rose to amounts in mice that were never calorie restricted. We
conclude that adult mice have endogenous programs to destroy and
regenerate alveoli, thereby raising the danger of inappropriate activation but the possibility of therapeutic induction, if similar programs exist in humans.
oxygen consumption; calorie restriction; apoptosis; cell replication
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