Abstract
It is uncertain whether Bmi-1 deficiency could lead to skin aging by redox imbalance and DNA damage. In this study, we first confirmed that Bmi-1 had a relatively high expression level in the skin and Bmi-1 expression levels gradually decreased with age. Then, we studied the role of Bmi-1 in the skin using a Bmi-1−/− mouse model. Bmi-1−/− mice were supplemented with or without pyrroloquinoline quinone (PQQ) for 5 weeks, and their skin phenotypes were compared with Bmi1−/− and wild-type littermates. Our results showed that Bmi-1−/− mice displayed decreased vertical thickness of skin, sparse hair follicles, and thinner and more irregular collagen bundles. Mechanistically, increased oxidative stress with reducing antioxidant capacity and induced DNA damage occurred in Bmi-1−/− mice. Subsequently, this would lead to reduced cell proliferation, increased cell senescence and matrix metalloproteinases (MMPs), and the degradation of fibroblast function and further reduce collagen synthesis. All pathological alterations in the skin of Bmi-1−/− mice were alleviated by PQQ supplementation. These results demonstrated that Bmi-1 might play a key role in protection from skin aging by maintaining redox balance and inhibiting DNA damage response and will be a novel and potential target for preventing skin aging.
Highlights
Skin aging is a complicated process which occurs under the influence of external factors or internal factors
We examined the changes in dermal morphology, proliferation, senescence, oxidative stress, and DNA damage to observe whether pyrroloquinoline quinone (PQQ) can prevent Bmi-1 deficiencyinduced skin aging
These results indicated that the effect of PQQ on the skin aging phenotypes of Bmi-1-/- mice may be associated with increasing cell proliferation and inhibiting cell senescence in skin
Summary
Skin aging is a complicated process which occurs under the influence of external factors (such as sunlight exposure, air pollution, smoking, alcohol, and malnutrition) or internal factors (such as age and genetic background). Previous reports support a primary role of Bmi-1 in the maintenance of human keratinocyte survival [13, 15] It is unclear whether Bmi-1 deficiency could lead to intrinsic skin aging by redox imbalance and DNA damage. Pyrroloquinoline quinone (PQQ) is an aromatic tricyclic o-quinone which has been proven to be an antioxidant that protects living cells from oxidative damage in vivo and the biomolecules from artificially produced reaction oxygen species in vitro [16]. It is unclear whether PQQ can prevent Bmi-1 deficiency-induced skin aging by inhibiting oxidative stress and DNA damage. This study will elucidate the role and mechanism of Bmi-1 in intrinsic skin aging and will provide a novel light for beauty
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