New Skin for the Old

… in mice, via skin grafting (not sure if this translates in any reasonable way to human therapeutic approaches… perhaps some of the dermatologists here can weigh in…)

Scientists at Haifa’s Rambam Health Care Campus and Israel’s Technion Institute reversed the aging of skin cells by grafting aged human skin in lab tests. The skin rejuvenated - even generating new blood vessels and improving age-related biomarkers. It represents a breakthrough for research into aging.

Research Paper Here:

Human organ rejuvenation by VEGF-A: Lessons from the skin

https://www.science.org/doi/10.1126/sciadv.abm6756

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This is fascinating stuff.
So we put old human skin on young mice and the old becomes young!

We put young skin on old mice and nothing happens.

We isolate the protein, vascular endothelial growth factor as the “ younging “ factor. That supports their theory of angiogenesis preventing aging.

There’s a problem here though. VEGF-A is also associated with metastatic cancer and in fact inhibiting it is one of the major mechanisms of rapamycin’s anti cancer effects.

So is this a trade off . In exchange for youth we get cancer? This same debate is still raging about telomeres.

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Could the difference be that in once case its tissue specific and perhaps shorter term, and in the other its systemic and longer term?

I once worked on a company where we were looking at IGF-1 as a potential application in terms of gene therapy for muscular dystrophy and also sarcopenia. While systemically IGF-1 is pro-aging, when over-expressed in muscles it is anti-aging (actually strengthening muscles long term, decreasing physical degradation and ultimately lengthening lifespan (in mice).

I’m wondering if many of these situations could be overcome with a local application either through gene therapy, etc. and avoiding systemic applications.

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biochemistry is not my specialty, in fact I am a metallurgist, but HIF-1 and VEGF are terms that I have come to know when reading about hbot, I also know that both factors are produced when there are injuries, I have read by example that microneedling stimulates to hif and vegf

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It’s a good idea. The local application would need to have minimal systemic absorption. I think titanium dioxide and zinc don’t absorb well.

I’m sort of wondering from this if rapamycin slows aging but in the process prevents its reversal. Could angiogenesis really be that important?

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Another approach:

Researchers are examining how to regenerate skin without scarring by reactivating Lef1 expression in adult fibroblasts to reprogram the skin.

Fibroblasts are cell types dominant in the dermis, the thick middle layer of skin. They are classified into subtypes, with each having a specific function and the potential to aid in healing wounds, said Sean Thompson, graduate student in the School of Molecular Biosciences for the College of Veterinary Medicine.

One subtype is the palitary fibroblast (PFs), a broad subtype of firbroblasts. Fs turn into dermal papillae, a cell type that sits at the base of the hair and signals hair growth. PFs are present in embryonic or young skin and degrade over time. They are absent in older skin, which prevents the regeneration of hair follicles and skin, along with scarring, Thompson said.

Young skin is able to fully regenerate without scarring due to PFs and the LEF1 transcription factor, a protein in young skin that can activate or deactivate genes in the DNA. Reactivation of LEF1 expression in adult fibroblasts could support regenerative outcomes, or “anti-aging,” he said.

A research team led by Ryan Driskell, assistant professor at the School of Molecular Biosciences, is researching how to reactivate the young gene and the Lef1 transcription factor in adult skin. The goal of the project is to reprogram adult skin to have younger properties and allow it to regenerate to its original state.