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How to make elderly human skin young again

Have scientists at Haifa’s Rambam Health Care Campus and the Technion-Israel Institute of Technology and colleagues abroad – after two decades of research – discovered the fountain of youth? This omnipresent human desire seems closer to fulfillment, at least in laboratory mice, on whom the researchers discovered a mechanism for rejuvenating human organs.

Conducted by Dr. Aviad Keren, Dr. Yaniv Keren, Prof. Yehuda Ullman, Prof. Amos Gilhar of the Haifa institutions, Dr. Marta Bertolini of the Monasterium Laboratory in Germany and Dr. Ralf Paus of the University of Manchester, the study has just been published in the prestigious journal Science Advances published by the American Association for the Advancement of Science under the title “Human organ rejuvenation by VEGF-A: Lessons from the skin.”  

Using an old skin graft on young mice, they proved that it is possible to make skin and other organs young again via a change in molecular structure through all the layers of the skin.

Transplanting aged human skin onto young mice with severe combined immunodeficiency disease (SCID) that genetically affects both B and T lymphocytes can rejuvenate the transplantation of living cells, tissues or organs from one species to another, they wrote. This is accompanied by angiogenesis (the growth of new blood vessels), repigmentation of the epidermis (outer layer of the skin) and significant improvements in vital biomarkers connected to aging.

Reversing aging

If one accepts the view that aging is “an ultimately a fatal disease whose progress can be slowed and reversed and views aging as a druggable and reprogrammable target, dissecting the key drivers of human organ aging and developing effective molecular strategies to prevent or even reverse it surely constitutes one of the most fundamental missions of biomedical research,” they wrote. 

To achieve this, aging-research models are critically needed in which not only the key drivers of human organ aging can be identified but also the most promising strategies to prevent getting old and to make humans young again through drugs that remove old cells can be tested on lab animals before using on patients, they continued. 

Human skin is ideally suited as such a preclinical aging research model but is rarely used by mainstream aging research for this purpose, but aging of the human body first becomes visible in changes of the skin changes and the graying of hair. 

“While massive industry efforts therefore cater to the ancient human desire to halt or reverse the phenotype of aging skin, success at this frontier has remained moderate at best, and many product claims of in-vivo [in animal models] rejuvenation of human skin are typically insufficiently substantiated.” /The study authors/

However, the molecular mechanisms that underlie skin aging in lab animals are becoming increasingly understood and seem possible, the researchers wrote. 

The team previously grafted aged human skin on SCID young mice, but they didn’t know whether the rejuvenation of skin that they witnessed extended below the epidermis. To determine this, they used vascular endothelial growth factor A (VEGF-A) to promote human organ rejuvenation in lab animals. 

The aging was were reversed when old human skin was transplanted on young SCID mice, thus confirming that all layers of human skin could become young again. In addition, the number of new blood vessels in the skin also increased. 

Judy Siegel-Itzkovich