The OneSkin Technologies DNA Methylation Clock for Assessment of Skin Aging

OneSkin Technologies is one of the first generation of startup biotech companies in the longevity industry; you'll find an overview of their programs and technology in an interview with founder Carolina Reis last year. In summary, OneSkin works on both improved models of aging skin, and topical senolytic compounds capable of selectively destroying the senescent cells thought to be responsible for a sizable fraction of skin aging in later life. Unlike other companies in the longevity industry, the OneSkin staff is focused on the cosmetics regulatory path to market. This is in some ways more limited, and in other ways much cheaper and faster than the standard investigational new drug approach with the FDA.

Today's news is more on the modelling front of the company's efforts, in that OneSkin has developed a DNA methylation clock for age assessment in skin. DNA methylation is a form of epigenetic mark on DNA, an adjustment as to whether or not a gene will be expressed to produce the protein that it encodes. These marks shift constantly in response to circumstances, but some changes are characteristic of aging. The first epigenetic clock to assess chronological age, and which showed acceleration of the epigenetic age in people with greater mortality risk, was developed a decade ago. Considerable effort since then has gone into producing ever more varied (and sometimes better) assessments of biological age.

Evidence to date has suggested that different organs age at different rates, or at least that the epigenetic response to the molecular damage of aging is consistently different in different tissues. This means that tissue specific epigenetic clocks are probably necessary as this technology becomes used in practical ways. The primary obstacle to that practical use is that there is all too little connection between these epigenetic marks and the known mechanisms and processes of aging. It is very unclear, in advance, as to whether any specific intervention or mechanism should be expected to change a measurement of epigenetic age, or, when changes are observed, whether those changes are meaningful. So the clocks must be calibrated for use with any specific intervention - and that is very much an ongoing process in its earliest stages at best.

OneSkin launches MolClock, the first skin-specific molecular clock to determine the biological age of human skin

OneSkin is excited to share our new application programming interface (API), MolClock, the first ever skin-specific molecular clock designed to determine the chronological age of human skin. MolClock has the potential to drastically transform how scientists measure an individual's skin molecular age which indicates one's overall health, and the efficacy of skin products and interventions from a molecular level. While OneSkin owns the proprietary rights of MolClock, the tool is available for free and public use in an effort to forward the study of molecular aging and longevity research for scientists everywhere.

"The algorithm behind MolClock was constructed using machine learning to detect important epigenetic alterations that occur in our skin as we age. To train and test the MolClock algorithm, we used over 500 human skin samples and over 2,000 DNA methylation (DNAm) markers, achieving a highly accurate DNAm age predictor. MolClock allows us to predict the molecular age of someone's skin based on their methylation profiles, which correlates strongly with one's chronological age. Exceptions occur when there are ongoing processes that influence one's DNAm age such as diseases including cancer and psoriasis, inflammatory disorders, and environmental exposures or lifestyle influences, such as smoking and obesity, which in most cases, will promote an acceleration of aging and increase the skin molecular age. Therefore, the DNAm age predicted by our tool is a highly accurate indicator of overall skin health."

Highly accurate skin-specific methylome analysis algorithm as a platform to screen and validate therapeutics for healthy aging

DNA methylation (DNAm) age constitutes a powerful tool to assess the molecular age and overall health status of biological samples. Recently, it has been shown that tissue-specific DNAm age predictors may present superior performance compared to the pan- or multi-tissue counterparts. The skin is the largest organ in the body and bears important roles, such as body temperature control, barrier function, and protection from external insults. As a consequence of the constant and intimate interaction between the skin and the environment, current DNAm estimators, routinely trained using internal tissues which are influenced by other stimuli, are mostly inadequate to accurately predict skin DNAm age.

In the present study, we developed a highly accurate skin-specific DNAm age predictor, using DNAm data obtained from 508 human skin samples. Based on the analysis of 2,266 CpG sites, we accurately calculated the DNAm age of cultured skin cells and human skin biopsies. Age estimation was sensitive to the biological age of the donor, cell passage, skin disease status, as well as treatment with senotherapeutic drugs.

Comments

"Our findings have proven that the power of rejuvenating skin by reducing the DNAm age generated by our OneSkin proprietary peptide is superior than the compound most frequently used in the market. For this reason, we really value the scientific markers behind our OS-1 product"

A proprietary clock to sell a proprietary treatment? I'm looking forward to using their OS-1 product, and perhaps their clock, but they're going to have to make more sense of what exactly the clock is measuring, such as Boroni's discussion of collagen:

"...specific sites become hypermethylated and certain genes that are active when we are younger, turn off and therefore become dormant due to age-induced hypermethylation [ 2 ]. One example is collagen - as we age, a gene that produces a protein important for collagen production, SEC31, becomes hypermethylated, with more and more methyl groups added to the piece of DNA coding for this gene [ 2 ]. This gene hypermethylation-associated silencing plays an important role in the age-associated skin phenotype, likely leading to a reduced capacity of the cell to export the collagen protein. This reduction in collagen in our skin is one reason why our skin tends to be less firm when we get older."

Posted by: dtkamp at July 23rd, 2020 9:17 AM

I continue to see methylation clocks as a complex correlation vs causation quandary

Posted by: JohnD at July 24th, 2020 3:09 PM

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