Challenging The Paradigm For Impaired Healing In Aging
Michelle D. Bagood1, Daniel J. Yoon2, Daniel Fregoso2, Anthony Gallegos2, Lam T. Khuat1, Cordelia Dunai1, William J. Murphy, PhD2, R. Rivkah Isseroff, MD2.
1UC Davis Graduate Group in Immunology, Davis, CA, USA, 2UCD Institute for Regenerative Cures, Sacramento, CA, USA.
The generally accepted clinical dogma is that wound healing is delayed in aged individuals, however supporting evidence and mechanistic understanding are conflicting and incomplete. Older patients are known to have systemic inflammation and diminished immune responses, both of which may contribute to impaired healing. We hypothesized full-thickness cutaneous wounds would heal more slowly because of increased inflammation in aged (2+ yrs, equivalent to 69+ y.o. humans) compared to young (10-12 wks, equivalent to 20-25 y.o. humans) BALB/c mice. Contrary to our hypothesis, we found that aged mice trended toward better healing compared to young mice despite having greater weight loss. While the aged mice did show increased pro-inflammatory mediator gene and protein expression, they initiated pro-reparative immune responses such as increased wound IL-10 and TGFβ gene expression earlier than young mice, which combined may account for the comparable healing. Also potentially contributing to healing in aged animals was their elevated systemic level of dopamine, a catecholamine known to attenuate IL-8 effects, inhibit superoxide anion production, and induce neutrophil apoptosis, which are known to impair healing in sterile wounds. When repeated in male and female C57BL/6 aged and young mice to rule out sex and strain dependence, we found the same trend of equivalent healing with greater weight loss. While our results do not agree with popular consensus, it is evidence that wounds have deleterious effects on the overall health of the older wounded individual. An additional stress, such as wound infection, may overwhelm the organism’s reparative functions, and result in impaired healing.
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