Our cells divide 2 trillion times each day, and each time our DNA has to replicate which damages the telomeres (protective caps) therefore causing damage to the genetic material. As we grow older the DNA damage is more profound, and the first to suffer is our skin. Our skin falls loose and loses the plumpness it once had, however, researchers at Babraham Institute, UK have developed a new technique to rejuvenate the skin and turn the cell clock about 30 years back! This is a revolutionary discovery, so let's take a look at the mechanism behind it.
figure 1.0 taken from science alert showing collagen production (in red) being restored in cells after reprogramming. (Fátima Santos, Babraham Institute)
The new method is called maturation phase transient reprogramming (MPTR), the essence of it is that it changes the body cells (somatic cells) to induced pluripotent stem cells (iPSCs) and re-differentiates them and this reverses the cell damage. Pluripotent cells are cells that are capable of specializing into multiple different cells, but when re-differentiated (specialized) these types of cells represent fetal cells and not adult cells. This was one of the issues the scientists have tackled. They found out that full reprogramming is not required to reverse the ageing of the somatic cells, thus giving rise to the MPTR method.
Dermal fibroblasts are the most common type of cells found in the connective tissue of the body such as the cartilage or adipose tissue. They secrete collagen proteins that are important to make your skin look plump and not become loose. The researchers used dermal fibroblasts from middle-aged candidates and came across an interesting property; the cells temporarily lose and then reacquire their fibroblast identity during MPTR, possibly as a result of epigenetic memory at enhancers and/or persistent expression of some fibroblast genes. They used this property to our advantage and found an optimum time to stop the reprogramming of the cell! The cells they tested on showed that the cell had aged back about 30 years, and the rejuvenation of the transcriptome as measured by a novel transcriptome clock is the most notable change.
The transcriptome is the full range of messenger RNA, or mRNA, molecules expressed by an organism. The mRNA molecules play an important role in protein synthesis (remember, collagen is an important protein for skin health!) therefore reversing the ageing of the cell. They also observed significant changes in the H3K9me3 histone methylation (a biological process by which methyl groups are added to the DNA molecule causing it to tighten.) levels and the DNA methylation ageing clock that lead to changes in genes such as APBA2 and MAP that are responsible for age-linked problems such as Alzheimer’s and cataracts.
Their method has reversed the ageing clock more than before. They successfully showed that complete reprogramming does not result in greater restoration of cellular age instead optimal time windows exist. Maturation phase transient reprogramming opens up possibilities for treating an array of age-related diseases and faster wound healing.
Researchers - Diljeet Gill, Aled Parry, Fátima Santos, Hanneke Okkenhaug, Christopher D Todd, Irene Hernando-Herráez, Thomas M Stubbs, Inês Milagre and Wolf Reik
Written by Sakshi Deshpande
Edited by Svasti Tewari
Bibliography
Gill, Diljeet, et al. “Multi-Omic Rejuvenation of Human Cells by Maturation Phase Transient Reprogramming.” ELife, ELife Sciences Publications, Ltd, 8 Apr. 2022, https://elifesciences.org/articles/71624.
Kakkad, Ria. “A Revolutionary Technique to Rejuvenate Skin Cells.” Drug Target Review, 8 Apr. 2022, https://www.drugtargetreview.com/news/102617/a-revolutionary-technique-to-rejuvenate-skin-cells/.
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