Abstract
Skin chronically exposed to sun results in phenotypic changes referred as photoaging. This aspect of aging has been studied extensively through genomic and proteomic tools. Metabolites, the end product are generated as a result of biochemical reactions are often studied as a culmination of complex interplay of gene and protein expression. In this study, we focused exclusively on the metabolome to study effects from sun-exposed and sun-protected skin sites from 25 human subjects. We generated a highly accurate metabolomic signature for the skin that is exposed to sun. Biochemical pathway analysis from this data set showed that sun-exposed skin resides under high oxidative stress and the chains of reactions to produce these metabolites are inclined toward catabolism rather than anabolism. These catabolic activities persuade the skin cells to generate metabolites through the salvage pathway instead of de novo synthesis pathways. Metabolomic profile suggests catabolic pathways and reactive oxygen species operate in a feed forward fashion to alter the biology of sun exposed skin.
Highlights
Skin is the largest and one of the most complex organs in human body, accounting for almost 15% of total body weight
Global metabolomics profile Probing the metabolome of 50 paired skin samples obtained from sun-exposed and sun-protected sites, through mass spectrometry, we quantified a total of 241 metabolites
While studying sun-exposed skin we identified three NAD+ metabolites; nicotinamide adenine dinucleotide (NAD), nicotinamide ribonucleotide (NMN) and nicotine riboside (NR), which were significantly increased compared to sunprotected skin (Figure 6)
Summary
Skin is the largest and one of the most complex organs in human body, accounting for almost 15% of total body weight. It serves as an important environmental interface and acts as a first line of defense against various environmental insults. The phenotypic changes often manifest in the skin as pigmentation abnormalities, epidermal thickening, erythema and others. These changes are due to alterations in various biological responses including DNA damage[4] inflammation, immune suppression [5], oxidative stress, hyperplastic responses in skin [6] as well as perturbed hormonal balances[7]
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