Abstract
Does the longevity phenotype offer an advantage in wound healing (WH)? In an attempt to answer this question, we explored skin wound healing in the long-lived transgenic αMUPA mice, a unique model of genetically extended life span. These mice spontaneously eat less, preserve their body mass, are more resistant to spontaneous and induced tumorigenesis and live longer, thus greatly mimicking the effects of caloric restriction (CR). We found that αMUPA mice showed a much slower age-related decline in the rate of WH than their wild-type counterparts (FVB/N). After full closure of the wound, gene expression in the skin of old αMUPA mice returned close to basal levels. In contrast, old FVB/N mice still exhibited significant upregulation of genes associated with growth-promoting pathways, apoptosis and cell-cell/cell-extra cellular matrix interaction, indicating an ongoing tissue remodeling or an inability to properly shut down the repair process. It appears that the CR-like longevity phenotype is associated with more balanced and efficient WH mechanisms in old age, which could ensure a long-term survival advantage.
Highlights
The skin is the first and foremost natural barrier of the organism against foreign infection and hazards
In view of using αMUPA mice as a caloric restriction (CR)-mimicking model to study the impact of CR on skin WH (SWH), it is important to stress that the αMUPA mice strongly express the urokinase-type plasminogen activator (uPA) in the ocular lens and ectopically in the brain but not in the skin [17], excluding the gene-specific effects on SWH
When comparing gene expression in the intact skin, we surprisingly found that there were no significant differences between young αMUPA and wild type (WT) mice (0 genes differentially expressed with at least twofold changes and p-value < 0.01; even under less stringent conditions [p-value < 0.05] there were only 2 differentially expressed genes)
Summary
The skin is the first and foremost natural barrier of the organism against foreign infection and hazards. Even in case of calorie restriction (CR), one of the most successful longevity-promoting interventions in mammals (for recent reviews see [12,13]), the few studies conducted far did not bring about decisive results [14,15,16] To address this issue, we investigated SWH in the longlived transgenic αMUPA mice, a unique genetic model of extended lifespan. Being initially generated in 1987 to investigate a potential role of uPA in eye pathologies (e.g. cataract and glaucoma), these transgenic mice were unexpectedly found to display a longevity phenotype Compared to their wild type (WT) counterparts, the αMUPA mice spontaneously eat less when fed ad libitum, and live longer [18]. In view of using αMUPA mice as a CR-mimicking model to study the impact of CR on SWH, it is important to stress that the αMUPA mice strongly express the uPA in the ocular lens and ectopically in the brain but not in the skin [17], excluding the gene-specific effects on SWH
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