In my Science of Aging supplement for my plastic surgery journal, they had this article. The actual title is “Targeting Alternative Splicing for Reversal of Cellular Senscence in the Context of Aesthetic Aging.” If you only understood a word or two of that title, I am with you. Super science-y stuff here.
What they wrote about:
Skin is important. It is the primary protection against external injuries, it helps maintain body homeostasis, it defends against the environment and chemicals and sun. Because it is exposed (not inside the body like other organs), you get to see it aging. Aging skin changes in thickness, pigment, and elasticity. It loses the fat under the surface. It becomes more fragile and doesn’t heal as well.
Cellular Senescense is a “state of stable cell cycle arrest that is linked with cellular and tissue aging.” Targeted removal of senescent cells benefits the healthspan and lifespan in animal models. The question is can you get rid of these senescent cells? Or can you rejuvenate them? So this paper looks at different strategies to try to remove or reverse senescent cells.
The players in cell aging:
EXTRACELLULAR MATRIX (ECM). This is a matrix of collagen, elastin, glycoprotein, fibronectin and other stuff. It is made by fibroblasts. Aging changes? Change to the elastin and collagen and dysfunction of fibroblasts.
HALLMARKS OF AGING:
- genetic instability
- telomere attrition
- altered proteostasis (change in protein production)
- epigenetic alterations (chemical modifications to DNA and RNA)
- Dysregulated nutrient signaling
- dysfunctional cellular communication
- stem cell exhaustion (depletion of the stem cell pool)
- mitochondrial dyspfunction (changes to mitchondria and leakage or reactive oxygen species)
- cellular sensence (accumulation of aged cells)
CELLULAR SENESCENCE. This is that cells get old. And when they do, they start to change: they don’t cycle like they should, they become enlarged and flatter, and they start to release markers thought to be contributors to chronic inflammation.
Skin aging is thought to be due to this cellular senescence of fibroblasts and keratinocytes (skin cells).
STRATEGIES TO FIGHT CELL AGING.
- Strategy One: get rid of the senescent cells. There have been studies with small molecules that get rid of the senescent cells. They found in animal studies improvement in lung, bone, cardiac, liver, and blood function, as well as reducing frailty, helping the kidney function, and helping hair growth. Initial human trials are going on, but small scale phase 1 trials using dasatinib and quercetin in patients with end stage lung fibrosis have shown promise, BUT it may not give long term success.
- Strategy Two: Try to control the bad stuff the senescent cells do (like don’t let them release the chronic inflammatory stuff). Antioxidants, antiinflammatory agents, and other things have been tried here. The risk with many of these agents is – like telomere treatments- do these lead to unexpected issues like increased cancer formation?
- Strategy Three: Alternative Splicing. This is getting super science-y In this treatment, a single gene can make a bunch of mRNA isoforms, which causes genome diversity, plasticity, and adaptability. The more adaptable your cells are, the better they respond to stress, and the less you cause senescence. Kid you not, in the paragraphs detailing how they do this, they use a “sliceosome” to cut and paste into the the mRNA.
So why do plastic surgeons care about this stuff?
Crazy enough, I have found plastic surgeons to be among the most inquisitive and creative of the surgical fields. What I do now for surgery is so different than what I did 10 years ago. Stem cells, growth factors, scarring, microsurgical techniques, skin transfer, fat transfer, nerve grafting. These are all areas of research for plastic surgeons.
The fact here is that aging skin cells make you look old. They wrinkle, form pigment, sag and droop. If we could figure out how to make the skin cells not age (senescence), then we would effectively “rejuvenate the skin from the inside”. The issue with all of this is to prove these new treatments work, make sure they are safe, and figure out how to give them- topical? microneedle? injectable? diet?
As it is now, I do lots of fat transfer to the face to try to replace the subcutaneous fat you lose as you age. I use serums and peels to try to improve collagen and elastin in the skin. But these are bandaids. They are not stopping the aging.
If we could actually make your skin cells function like they did when you are younger? That is the holy grail.