Skin Wrinkles Drive Aging

August 27, 2023

Skin Wrinkles Drive Aging

We age. Our skin ages. Bummer. Our skin is our largest organ and provides an amazing protection from all the nasty things in our environment. It has collagen providing firmness, elastin adding elasticity and rebound, and glycosaminoglycans to maintain hydration. They are all abundant in young, healthy, unwrinkled skin. It should be noted that under a microscope of a biopsy of a wrinkle, there are no obvious indications that you are looking at a wrinkle. What gives?

There are two types of aging to skin. Intrinsic aging is going on inside the cells. Collagen drops by about 1% a year. Skin cholesterol decreases with aging and correlates with reduction of production of Vitamin D. Sweat and oil glands make less product, elastin production drops, and glycosaminoglycans are diminished. Older skin is naturally dryer. All this leads to mild, fine wrinkles.

Extrinsic aging occurs on top of intrinsic aging. Exposure to many forms of environmental damage will suffice. Excessive sun, tobacco use, and any number of environmental pollutants will do. Extrinsic aging shows up as thickening of the cornified layer, precancerous changes such as lesions called actinic keratosis, skin cancers, freckles, and upregulated loss of collagen, elastin, and glycosaminoglycans. These processes layered onto intrinsic aging make skin look rougher, with uneven tone, brown patches, thinner skin, and deep wrinkles

With advances in our understanding of senescent cells and the processes they go through, skin senescence is gaining greater understanding. The process that limits the cell division number is termed cellular or replicative senescence. That is thought to be a powerful, albeit imperfect, tumor suppressive mechanism. It is also thought to contribute to organismic aging. Senescent cells undergo three types of changes: they irreversibly arrest growth, they acquire resistance to the natural recycling call apoptosis, and they acquire altered differentiated functions.

It's that "altered differentiated function" that may be the root problem. That's a polite way of saying "They become zombies". The problem with zombies is that they freak out their neighbors. The skin, being such a large organ (#1 in size, competing with our vascular tree) is that when it misbehaves, the rest of the organism is affected. Senescent cells affect the cells around them and convert them into senescent cells. The general principle of aging is to keep cells "quiescent". Like soldiers on parade, dressed with rifles over their shoulders. quiescent cells are dressed up and ready to go. Senescent cells are like soldiers in their barracks, no rifles, wearing only their underwear, deep into a poker game with a beer in their hands, and not paying any attention to the enemy.

How do we affect that? That's the anti-aging rub. David Sinclair's research with metformin and NAD kicked off this idea. Tartary buckwheat is probably next on the list. It has been proven to lower epigenetic age. What we don't have is a direct measured link between skin wrinkles and aging. We just have teaser questions and epidemiology. Vitamin D is so intrinsic to aging, the loss of cholesterol in skin and subsequent loss of Vitamin D production suggests there is some link there. (Your natural D production has dropped some 80% by age 70)

www.What will Work for me. Well, well. It's the end of summer and the end of Vitamin D production. I am sloppy about sun block but I don't seek out sunlight. I don't smoke. But I'm wrinkled. As the famously old French woman, Jeanne Calmet, said, "I only have one wrinkle, and I'm sitting on it." She was very wrinkled, but at least had a sense of humor. I have started adding senolytic therapy to my regimen. Tartary buckwheat is a not topic. My only complaint is the number of pills I take. Oh well, .... I do take my 5,000 IU of D a day. That may be the simplest, most bang for your buck.

References: New Scientist, Scientific American, JBC, Jr Investigative Dermatology, Int Jr Mol Sci,Food Chem, Derm Surg, CNBC,

Pop Quiz

1. How much Vitamin D do you lose with aging?                           Answer: About 80% by age 70.

2. Why do you lose Vitamin D?                     Answer: Because we have lost the cholesterol content of our skin, which correlates with wrinkles.

3. What is wrong with a senescent cell?                      Answer: It acts like a zombie and damages the cell around it.

4. Why is skin senescence such a big problem?                          Answer: Because our skin is so big, it affects everything underneath. Instead of being a passive marker, it may be a driver of aging.

5. Do we have proof of this idea?                 Answer: No, it's just a conjecture, based on a lot of physiology that lines up. But an interesting point never the less.