The immune system undergoes marked changes during aging characterized by a state of chronic, low-grade inflammation, so called inflammaging. Domestic dogs are the most morphological and physiological diverse group of mammals, with the widest range in body masses for a single species. Additionally, smaller dogs tend to live significantly longer than larger dogs across all breeds. Body mass is intricately linked to mass-specific metabolism and aging rates, thus, dogs are exemplary for studies in inflammaging. Dermal fibroblasts cells play an important role in skin inflammation, and as such, are a good cell type to determine inflammatory patterns in dogs. Here, we examine aerobic and glycolytic cellular metabolism, and IL-6 concentrations in primary fibroblast cells isolated from small and large, young and old dogs when treated with lipopolysaccharide (LPS) from Escherichia coli to stimulate an inflammatory phenotype. We found no differences in cellular metabolism of any group when treated with LPS. Unlike mice and humans, there was a less drastic amplification of IL-6 concentration after LPS treatment in the geriatric population of dogs compared with puppies. We also found evidence that large breed puppies have significantly less background or control IL-6 concentrations compared with small breed puppies. This implies that the patterns of inflammaging in dogs may be distinct and different from other mammals commonly studied.
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The Beneficial Regulation of Extracellular Matrix and Heat Shock Proteins, and the Inhibition of Cellular Oxidative Stress E ects and Inflammatory Cytokines by 1-alpha, 25 dihydroxyvitaminD3 in Non-Irradiated and Ultraviolet Radiated Dermal Fibroblasts
Intrinsic skin aging and photoaging, from exposure to ultraviolet (UV) radiation,
are associated with altered regulation of genes associated with the extracellular matrix (ECM) and inflammation, as well as cellular damage from oxidative stress. The regulatory properties of 1-alpha, 25dihydroxyvitamin D3 (vitamin D) include endocrine, ECM regulation, cell differentiation, photoprotection, and anti-inflammation. The goal of this research was to identify the beneficial effects
of vitamin D in preventing intrinsic skin aging and photoaging, through its direct effects as well as its effects on the ECM, associated heat shock proteins (HSP-47, and -70), cellular oxidative stress effects, and inflammatory cytokines [interleukin (IL)-1 and IL-8] in non-irradiated, UVA-radiated, UVB-radiated dermal fibroblasts. With regard to the ECM, vitamin D stimulated type I collagen and inhibited cellular elastase activity in non-irradiated fibroblasts; and stimulated type I collagen and HSP-47, and inhibited elastin expression and elastase activity in UVA-radiated dermal fibroblasts. With regard to cellular protection, vitamin D inhibited oxidative damage to DNA, RNA, and lipids in
non-irradiated, UVA-radiated and UVB-radiated fibroblasts, and, in addition, increased cell viability of UVB-radiated cells. With regard to anti-inflammation, vitamin D inhibited expression of Il-1 and IL-8 in UVA-radiated fibroblasts, and stimulated HSP-70 in UVA-radiated and UVB-radiated fibroblasts. Overall, vitamin D is predominantly beneficial in preventing UVA-radiation induced
photoaging through the differential regulation of the ECM, HSPs, and inflammatory cytokines, and protective effects on the cellular biomolecules. It is also beneficial in preventing UVB-radiation associated photoaging through the stimulation of cell viability and HSP-70, and the inhibition of cellular oxidative damage, and in preventing intrinsic aging through the stimulation of type I collagen and inhibition of cellular oxidative damage.
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- Award ID(s):
- 1909824
- NSF-PAR ID:
- 10212791
- Date Published:
- Journal Name:
- Cosmetics
- Volume:
- 4
- ISSN:
- 2079-9284
- Page Range / eLocation ID:
- 46-51
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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