Warning: this is a “heavy” post that may feel to you like you are back in school and not in a good way (like for prom). You don’t have to read it but the objective is to convey to you the complexity of skin metabolism and molecular biology and why you should never look for a “magic” ingredient when it comes to skin youth and health. In short, life (LIFE) is complicated.
Your skin is alive. Below the few layers of dead cells in the epidermis, perfectly designed for the tough job of protecting your body from pollution and damage, is the basal cell layer. Here is your stem cells lay, semi dormant, until needed. When they are needed (wound either accidental or provoked like by a peel), they will divide and soon after, will go back to sleep.
The daughter cells divide a few times, the successful cells producing the deeper layers of the epidermis. What do I mean by “successful”? This is the secret for healthy skin that does not thin into nothing as you age. An excellent scientific publication, published this year (Liu et al., 2019), explain the secret for success.
Let’s start with stem cells.
What are stem cells?
Stem cells are undifferentiated cells characterized by their capacity for self-renewal and differentiation into various cell types. In other words: while most lung cells that divide (called progenitor cells) can only form other lung cells of the same type, stem cells (much rarer in adult lungs) can divide to make other types of cells.
Do plants have stem cells?
Yes. From your high school times you may remember meristems, phloem, xylem, etc. But orchid stem cells are only useful to orchids. With orchid’s DNA in the stem cells, the plant will be able to make xylem, phloem, buds, roots, leaves, etc. Just as every plant has its own stem cells, and only each plant own stem cells will be of any use. What can a rose bush do with orange stem cells? Nothing. Even in grafting (like orange on orange) stem cells don’t mix as such. And they will be useful only if they are intact, alive and in the right place at the right time. Otherwise, they are just as useful as… nothing.
It is obvious to me that orange juice will not help an orange tree, and orchid stem cells extract will not help orchids. You need live, intact cells to be able to do the job of dividing, making new cells that will “prosper”. Apple stem cells extract, orchid stem cells extract, etc., are a juice just as the ones you make for your breakfast.
Go ahead, eat an apple, buy yourself an orchid (or visit the botanical garden) but please remember that these days, plant Latin names are “used in vain” by skin care companies all the time in what the industry calls “label value”.
Fruit and plant juices can also be used as a Trojan horse for undesirable preservatives that need not be disclosed under FDA rules because they are “part of the manufacturing process”. In short, there are many reasons to avoid using products containing stem cells of anything.
Do we, humans, have stem cells?
Yes! We need them, especially in tissues like skin, where the cells are “destined” to die to fulfill their job. Our epidermis is made of dead cells, this is the way it can be such a great barrier to water loss. But, if skin cells keep dying, where are the new cells coming from? Since the epidermis is highly susceptible to injury, resident stem cells are crucial for maintaining both the status quo and repair the skin when it is damaged. Stem cell division and differentiation compensates for cell loss.
The “life cycle” of skin stem cells
One of the most significant research papers to come out in recent years is the one by Liu et al. (2019), named “Stem cell competition orchestrates skin homeostasis and ageing”. In this paper, the authors show, by using a variety of methods (another plus) that the presence of a “good” collagen 17 protein is very important for the success of stem cells when it comes to succeeding in the competition for space and survival. A cell that is expressing collagen 17 will multiply and prosper, and one that does not express this protein will divide in the wrong way and disappear from our skin rapidly, without leaving “daughter cells” to maintain the skin barrier. Apocynin gives an advantage in this tough competition, by promoting the synthesis of collagen 17 and increasing the chances for survival of the mother cells derived from your stem cells. This is how apocyinin prevents skin aging.
Liu et al. (2019) showed that the collagen protein COL17A1 can “sense” DNA damage. In young skin, DNA damage in a small number of epidermal stem cells promotes COL17A1 degradation, decreasing the formation of hemidesmosomes, the multiprotein structures that anchor basal-layer epidermal cells to the basement membrane. This is the membrane that connects the epidermis to the dermis. Stem cells with high COL17A1 levels and high numbers of hemidesmosomes (‘fit’ cells) keep skin youthful by spreading along the basement membrane through parallel cell divisions and displacing (red arrows) poorly attached ‘less fit’ cells (orange) that have low COL17A1 levels. “Unfit” cells undergo perpendicular cell divisions and end up in the more superficial layers of the skin, shedding soon after. Ageing, radiation and certain genetic conditions cause a more general COL17A1 loss, causing thinning of the skin. If COL17A1 expression can be restored in stem cells, these cells divide and generate healthy skin.
Which ingredients work for stem cells?
Any active that prevents cell damage and DNA mutation will be good for your stem cells. UV radiation and Reactive Oxygen Species (ROS*) will reach deep into the skin and affect the stem cells present in the basal skin layer. Also, actives that promote a good “anchorage” of stem cells to the dermal epidermal junction. Have a look here at my post on apocynin. Plus actives that promote nutrition and provide “building blocks” that the skin can’t make itself, like essential fatty acids.
Which ingredients are useless?
Label value ingredients like plant stem cells extracts.
What about bad ingredients?
Those that promote oxidative stress and inflammation, including benzoyl peroxide, and allergenic fragrances and essential oils.
How to help your stem cells remain healthy
It is in your best interest to prevent mutations in your skin stem cells. Healing and skin renewal depends on the availability and genetic health of stem cells in the basal layer of the epidermis. In the basal cells you have long lived stem cells. Even in people with dark skin, stem cells accumulate DNA damage
Protect your sin from UV radiation by avoiding the sun, wearing a hat and sunscreen. Protect your skin from ROS* by using antioxidants that are effective in protecting your skin from oxidative stress. And protect your skin from ingredients known to cause oxidative stress like peroxides (benzoyl peroxide included!) and hydroquinone. Many of the “fast and furious” skin treatments will age your skin and can cause worse trouble in the long term.
Anchors for your stem cells and its descendants
Give your skin stem cells and daughter cells a helping hand. Some actives will promote the anchoring of the nascent cells to the dermal/epidermal junction increasing the chances that they will become part of your skin and not be lost while your skin gets thinner. Go for apocynin to promote the synthesis of collagen COL17A1.
And, finally, about telomeres and sirtuins
First, telomeres. Read here about the scientist, Barbara McClintock, who predicted the existence of telomeres long before they were discovered.
Telomeres protect the end of chromosomes from deterioration and from fusion with other chromosomes. Because of the way DNA replication works in eukaryotes, including us, humans, telomeres shrink a bit every time a cell divides. In humans, telomere shortening is associated with aging.
Telomerase is an enzyme that “replenishes” the telomere “cap” of the DNA. However, in most multicellular eukaryotic organisms, telomerase is active only in germ cells, some types of stem cells such as embryonic stem cells, and in certain white blood cells. This is not bad, because the steady shortening of telomeres with each replication in body cells may prevent cancer.
Oxidative stress accelerates the shortening of telomeres, one more reason why it is useful to prevent it using antioxidants.
Sirtuins (see also this blog post) are enzymes (NAD+-dependent deacylases) found in humans, yeast, worms, flies, and mice. Sirtuins are proteins with a very important role in the cell: they control the enzyme that converts acetate, a source of calories, into acetyl CoA, a key point of entry to cellular respiration. Because of this crucial role, it has been proposed that it may be possible to control age-related disorders in various organisms, and in humans. These disorders include obesity, metabolic syndrome, type II diabetes mellitus, Parkinson’s disease and the “ultimate disorder”: aging. Sirtuins are regulators of aging and longevity, and respond to nutritional and environmental perturbations, such as fasting, DNA damage, dietary restriction and oxidative stress. In general, sirtuin activation triggers DNA transcription in a way that increases metabolic efficiency, stimulates mitochondrial oxidative metabolism and resistance to oxidative stress. Sirtuins increase anti-oxidant pathways and facilitate DNA damage repair through chemical modification of repair proteins. Besides promoting longevity, sirtuins can alleviate many diseases of aging, including type 2 diabetes, cancer, cardiovascular diseases, neurodegenerative diseases, and pro-inflammatory diseases.
Suppression of cellular senescence by sirtuins seems to be through their delaying effect of age-related telomere shortening, promotion of genome integrity and repair of DNA damage.
Interesting fact: resveratrol is produced by plants in response to infections by pathogens or injury. It may even help with fungal infection in humans! Plus, it is an antioxidant.
Actives that help your skin through their action on stem cells, telomeres and/or sirtuins
ROS BioNet: will protect your skin from oxidative stress and make telomeres last longer.
Apocynin inhibits an enzyme, NADPH oxidase, that increases oxidative stress by producing ROS* (reactive oxygen species). Use apocynin and decrease oxidative stress. Apocynin promotes the synthesis of a COL17A1 crucial for the anchoring of newly formed stem cells, and its end effect will be to accelerate healing, delay aging and promote skin health. When it comes to hair, stem cells that make collagen 17 will keep producing hair, rather than becoming just one more skin cell (and there goes your hair!). We can expect that apocynin, by promoting collagen 17, will prevent hair loss. And we know that it should decrease oxidative stress and slow hair greying. Apocynin does even more: it also decreases inflammation, an enemy of our skin and hair, by decreasing oxidative stress through the inhibition of NADP(H) oxidase and oxidative stress. If you have to face a polluted environment when you are stuck in traffic, apocynin will help your SAS ROS* terminator to protect you.
Resveratrol, NAD+, pterostilbene. and other actives promote the activity of sirtuins. NAD+ because it is a substrate.
Liu et al (2019) Stem cell competition orchestrates skin homeostasis and ageing, Nature, 568:1-7
Wound healing: a cellular perspective. Melanie Rodrigues, Nina Kosaric, Clark A. Bonham, and Geoffrey C. Gurtner (2019) Physiol Rev 99: 665–706, doi:10.1152/physrev.00067.2017
Donati G, Rognoni E, Hiratsuka T, Liakath-Ali K, Hoste E, Kar G, Kayikci M, Russell R,Kretzschmar K, Mulder KW, Teichmann SA, Watt FM. Wounding induces dedifferentiation of epidermal Gata6(+) cells and acquisition of stem cell properties.Nat CellBiol19: 603–613, 2017. doi:10.1038/ncb3532
Imokawa, G., Kobayasi, T., and Miyagishi, M. (2000) Intracellular signaling mechanisms leading to synergistic effects of endothelin-1 and stem cell factor on proliferation of cultured human melanocytes. Cross-talk via trans-activation of the tyrosine kinase c-kit receptor.J. Biol. Chem. 27: 33321–33328.
Hattori, H., Kawashima, M., Ichikawa, Y., and Imokawa, G.(2004) The epidermal stem cell factor is over-expressed in lentigo senilis: implication for the mechanism of hyperpigmentation. J. Invest. Dermatol.122,1256 –1265