|Torres, Daniel - BAYLOR COLLEGE MED|
|George, Jessy - BAYLOR COLLEGE MED|
|Ellis, Steven - CLEMSON UNIVERSITY|
|Fiorotto, Marta - BAYLOR COLLEGE MED|
Submitted to: Experimental Gerontology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: February 10, 2005
Publication Date: March 1, 2006
Citation: Hadsell, D.L., Torres, D., George, J., Capuco, A.V., Ellis, S.E., Fiorotto, M.L. 2006. Changes in secretory cell turnover, and mitochondrial oxidative damage in the mouse mammary gland during a single prolonged lactation cycle suggest the possibility of accelerated cellular aging. Experimental Gerontology. 41(3):271-281. Interpretive Summary: During prolonged lactation, milk production rates declines through a process we refer to as secretory diminution. The goal of this study was to determine if aging of the mammary secretory cells was the cause of secretory diminution in the mouse. For this study we measured markers of oxidative damage in the energy producing organelles of mammary gland cells, mitochondria. An increase in oxidative damage to mammary mitochondrial DNA along with increased rates of mammary cell death indicated that an accelerated aging process had occurred. These studies may help us understand why milk production rates decrease during the declining phase of lactation.
Technical Abstract: Milk synthesis by the mammary gland declines during prolonged lactation despite the continued suckling stimulus and complete removal of mammary secretions. Although this process has been hypothesized to result from cellular aging there has been no reported analysis of aging markers in the lactating mammary gland. The goal of these studies was to relate lactation performance in the mouse during a single prolonged lactation cycle to changes in mammary development and mitochondrial oxidative damage. During an artificially prolonged lactation cycle, the capacity of the dams to support litter growth decreased over time. This decrease was associated with decreased mammary epithelial content. Cell proliferation, along with the percentage of mammary progenitor cells, was high during early lactation, but low during prolonged lactation. Apoptosis increased during prolonged lactation. Oxidative damage to mitochondrial DNA increased during the early postpartum period and remained elevated through the end of the cycle. In contrast oxidative damage to mitochondrial protein was high during early lactation and decreased through mid lactation to increase again with prolonged lactation. The results suggest that a single prolonged lactation cycle may replicate on an accelerated basis some of the changes that occur with a lifetime of aging in organs possessing more stable cell populations.