The skin is the largest human organ

The skin is the largest organ in the human body, accounting for about 16% of body weight. The skin consists of the dermis and the epidermis: the epidermis is the outer layer of the skin and consists of the stratum corneum, the stratum hyaline, the stratum granulosum, the stratum spinosum and the stratum germinatum from the outside to the inside. The cells of the stratum germinatum constantly divide and keratinize to replenish the shed stratum corneum; the dermis is composed of connective tissue, consisting of a papillary layer and a reticular layer from the outside to the inside, containing abundant mechanoreceptors, hair follicles, sweat glands, sebaceous glands, lymphatic vessels and blood vessels. There is a thin fibrous layer between the epidermis and dermis that controls the exchange of cellular molecules between the epidermis and dermis.

Functions of the skin

The function of the skin is important. Skin can protect tissues and organs in the body and block pathogen invasion; it control evaporation, maintain body water; it prevent the infiltration of external water; it stores water and synthesizes vitamin D; it absorb drugs; it excrete metabolic waste, regulate body temperature; It is also an important organ for us to perceive external stimuli

Keywords: skin metabolomics; Disease diagnosis; Personalized skin care

Metabolites in skin

The skin is not just a simple " few layers of cells, " but the skin tissue retains many detectable small molecule compounds.

Stratum corneum: between the dead flat keratinocytes of the stratum corneum there is a lipid matrix composed of a variety of small molecules, the most abundant of which are ceramide (Cer), cholesterol (Chol) and free fatty acids (FA); the rest of the components include triglycerides (Triglyceride, TAG), diglycerides (Diglyceride, TAG), and fatty acids (FA). Triglyceride (TAG), diglyceride (DAG), and cholesterol esters (CE). The stratum corneum also contains some proteolytic products and metabolites of sebum and sweat origin.

Sebum: It is mainly secreted by sebaceous glands, and is a complex collection of several lipids, including wax lipids, triglycerides, free fatty acids, but also mixed with phospholipids and cholesterol lipids that are produced by epithelial cell metabolism. Sweat: the composition of sweat is more complex than expected and is composed of 98-99% moisture and 1-2% electrolytes, inorganic salts, amino acids, and free fatty acids. Sweat is secreted by sweat glands in the skin, which have two main types, exocrine and apocrine sweat glands, and the components of sweat secreted by these two types of sweat glands also differ. Eccrine sweat glands, also called small sweat glands, are found throughout almost all skin, and the main components of their secretions are bicarbonate, potassium, and sodium chloride, as well as other minor components (e.g., glucose, pyruvate, lactate, cytokines, immunoglobulins, antimicrobial peptides, etc.); Apocrine sweat glands are mainly distributed in axillary, areolar and other locations, and are released by secretory gland cells through budding of the cell membrane to release secretions, which contain a lot of lipids, proteins and sterols and other substances. Exogenous substances : some Exogenous substances can also be detected in the skin, such as applied drugs, cosmetics, etc. In addition to genetic factors, the various physiological and biochemical functions of the skin are closely related to its constitutive structure, and we can evaluate skin function by analyzing skin components in pursuit of improvement.

Understanding skin metabolomics

Skin metabolomics is the collection, detection and quantitative analysis of all small molecule compounds in the skin (including endogenous metabolites and exogenous small molecule compounds absorbed by the skin) using metabolomic approaches to study their relationship with disease, treatment, health care, and skin care.

01 Skin metabolome and disease

Many metabolic small molecules retained in the skin are associated with the metabolic processes of the body, and their association with disease can be made using metabolomics techniques. Recently, multiple findings have been reported showing that altered metabolites in skin can suggest disease initiation or altered physiological states, and demonstrate the potential of skin metabolomics for disease diagnosis, health assessment, and monitoring.

Parkinson’s disease: researchers have found altered levels of certain volatile organic compounds (VOC) in skin sebum from patients with Parkinson's disease compared with healthy individuals (hippurate, perillyl aldehyde, and eicosanes, among others), giving patients with Parkinson's disease a unique “odor”. These odorants have the potential to become emerging markers for early diagnosis of Parkinson's disease. The odor markers have been synthesized in the laboratory and will be studied and validated in a population-based cohort through three clinical phases.

Dermatologic and systemic diseases: Analysis of skin lipidomics has revealed alterations in lipid composition associated with dermatologic or systemic diseases such as atopic dermatitis, hereditary ichthyosis, a rare skin condition called Netherton Syndrome, and schizophrenia.

Disease detection using sweat: Biomarkers indicative of cystic fibrosis and lung cancer are also present in sweat. In addition, sweat from patients with uremia contains high concentrations of urea, which can also be an indicator of end-stage renal disease.

Blood glucose monitoring: Real-time blood glucose monitoring using skin extracellular fluid is also a promising new direction as a non-invasive, non-invasive assay.

Exogenous molecules: Some exogenous substances can also be detected in the skin, such as applied drugs and cosmetic ingredients. Non-invasive assays are the future trend for disease diagnosis and prediction. Skin metabolomic assays can provide a non-invasive, convenient and rapid detection method. With the progressive research on skin physiology and small molecule metabolites in skin, non-invasive skin small molecule metabolite testing is expected to become another optional, non-invasive way of clinical disease diagnosis and health assessment after blood, urine, stool and tissue testing.

02 Skin metabolome and personalized skin care

It is common for us to apply drugs to the epidermis to treat diseases or to use skin care products to improve skin quality, and we expect the active ingredients to penetrate the skin and be absorbed and utilized by the body. Metabolomic techniques can help us to deepen our understanding of the physiological mechanisms of the skin, explain the pathways of exogenous substances involved in skin metabolism, internal and external factors affecting skin absorption, and help us to develop new drugs and skin care products for transdermal absorption or to evaluate the safety of cosmetics.

Circadian rhythms of the skin: An example of using metabolomics technology to better understand individual differences in skin physiology is the study of skin circadian rhythms by a team led by Dr. Nadine Pernodet of The Estée Lauder Companies Inc. By comparing the metabolomes of healthy skin at the age of 20-25 and the skin of the 60-year-old, she found that young and healthy skin has a distinct circadian rhythm, and the distribution of metabolites in the morning and evening is completely different. The skin at night is mainly repaired during the day. Skin damage caused by sunlight exposure and external environmental pollution, but aging skin gradually loses this natural rhythm, skin damage begins to accumulate, and visual skin aging gradually becomes obvious. The research results help product developers to further develop "humanized" skin care products that are more in line with the laws of skin physiology. In addition, for beauty seekers, skin aging, wrinkles, acne, allergies, redness, dryness, etc. are all critical issues. Identifying the skin metabolomic signatures that define these problems could make sense for cosmetic product developers to optimize product lines or for individual consumers to target and personalize care.

03 skin sample collection methods

Researchers can obtain biological samples for skin metabolomic studies through non-invasive and invasive sample collection methods, depending on the specific study population. Several studies using the skin metabolome for disease diagnosis (as described above) have used non-invasive sample collection because the former is more convenient and "non-invasive". There are three main sampling directions for non-invasive sample collection: stratum corneum, sebum, and sweat. Stratum corneum can be collected with polymer patches, such as D-Squame®; sebum can be collected with lipophilic film absorption, such as Sebutape®; and sweat has a sweat collector, such as Macroduct® . Invasive sample collection methods are tissue biopsy and suction blistering.

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Metanotitia’s R&D project of skin metabolism

Using our own high-resolution and high-precision mass spectrometry technology platform and long-accumulated practical experience in the development and application of metabolomics technologies, Metanotitia is conducting related research projects. We hope to deepen our understanding of the molecular mechanism of skin physiological metabolism with the help of metabolomic detection and analysis technology, establish skin classification based on skin metabolic characteristics, find specific biomarkers highly related to the occurrence of diseases, and further translate the research results into practical application fields such as clinical diagnosis, health evaluation, personalized skin care, new product development and product improvement. We have already completed the first batch of data collection and are in the process of organizing and analyzing the data. Please stay tuned with us.

Advantages of Metanotitia

With two high-resolution mass spectrometry detection platforms, LC-Orbitrap-MS and GC-TOF-MS, and a world-class database of metabolite standards, Metanotitia provides faster, more accurate and comprehensive identification of metabolites in samples. Our exclusive algorithms for integrating and analyzing different QC data can maximize the biological properties of samples, reduce detection noise, and detect >5000 highly comparable metabolic information from a single sample.