María Monterrubio

I often hear dermatologists say that, for skin anti-aging purposes, once you introduce retinol (or other retinoids) into your skincare routine, you should ideally apply it every day. Here I discuss my viewpoint on why that might not be optimal, based on science, my knowledge of skin biology, and my expertise with topical retinoids.

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Hi guys, and welcome! Let’s get to the root of the matter, aka the optimal frequency of use of retinol and other retinoids for skin youth-preserving purposes.

My experience with topical retinoids

I introduced topical retinoids into my facial skincare routine more than a year ago (in February 2021) after my dermatologist suggested a recovery boost after some acne rosacea episodes (and, why not, the preservation of my skin youth). She prescribed retinoic acid (tretinoin 0.015%), and I applied it once a week for a few months.

My skin felt good after that period. Tretinoin did not make it drier. It is not easy to get there with a low tretinoin dose (at least in my case, since my facial skin is pretty oily).

So that was not a problem for me (it could be for other people since retinoids may cause skin dryness). My skin handles retinoids pretty well and does not tend to get irritated by them.

However, I noticed that the typical over-peeling that often accompanies the beginning of a topical retinoid regimen was not going away as I expected after those initial months. 

Thus, I decided it was time for me to switch to a milder form of retinoid (specifically, retinaldehyde or retinal) that would make me feel more comfortable now that the rosacea struggles were under control. 

By the way, if you want to learn more about the types of retinoids available for purchase and how they work within the skin, you can look at my previous articles Smoothly kickstart retinoids and Why you should use retinoids in the summer.

I started with retinal once a week, then slowly worked my way up to three times per week (you can learn the approach I used in my previous article Smoothly Kickstart Retinoids).

A-Game 10. 0.1% Retinal Serum from Geek & Gorgeous

A-Game 5. 0.05% Retinal Serum from Geek & Gorgeous

Initially, of course, after switching from pure retinoic acid to retinal (which acts more indirectly), everything was running flawlessly (no noticeable extra skin peeling at all).

Yet, by the time I hit the three times a week goal, I perceived the over-peeling again. It was not too much. But enough to bother me since some facial skin areas were not the smooth slate I wished on the days I decided to put makeup on. 

Then I reduced the frequency of retinal to twice a week and eventually to once a week (the sweet spot where I am and plan to be for now, and possibly in the medium to long-term future).

Throughout that process, I kept thinking about whether applying a retinoid all the time wouldn’t cause skin troubles long-term. I refer to the (nearly) everyday application for prolonged periods (year after year) that some dermatologists suggest. 

I believe that despite all the benefits that retinoids undoubtedly provide to the skin, using them more sparingly might be more beneficial in the long run. I’ll tell you why.

Balancing skin renewal and exhaustion

Stem cells

The organs and systems of our body have the intrinsic ability to regenerate, repair themselves, and recover from injury. Some of them do it more often or faster than others. That is possible because of the presence of tissue-specific stem cells. 

Those cells self-renew and provide new cells to regenerate a given tissue. In other words, when they duplicate (see the image below), usually one daughter cell remains as a stem cell (and part of a tissue stem cell pool or reservoir), and the other assists in tissue regeneration (loses the ability of self-renewal, it differentiates).

The epidermis (the outermost layer of the skin) renews itself every few weeks throughout our lifetime and is in touch with the environment (constantly exposed to potential injury). Thus, it has tremendous potential for continuous regeneration and healing, thanks to stem cells.

Effects of retinoids on epidermal stem cells

As you can see in the image below, the epidermis comprises several layers of cells called keratinocytes (because they contain the protein keratin). The basal layer (the innermost layer situated right above the dermis) is the home of epidermal stem cells or basal keratinocytes. Those are highly proliferative cells that grow and multiply.

Roughly every three or four weeks, part of those basal keratinocytes become less proliferative. Then, they migrate upwards throughout the different layers until they reach the outermost cutaneous layers, where they die (thus becoming part of the stratum corneum, the layer that makes up the skin surface). 

Those superficial dead cells constantly shed off from the cutaneous surface (hence the skin renews itself). That process those less proliferative keratinocytes undergo until they die is called keratinocyte differentiation. 

Epidermal stem cells are also required to heal skin wounds. Another reason we need an epidermal stem cell reservoir to count on.

The biologically active form of all retinoids, retinoic acid, binds retinoic acid receptors inside the epidermal stem cells and stimulates cell growth.

As a result, the basal layer of the epidermis becomes thicker, more compact, and more organized. And so do the rest of the epidermal layers (including the superficial stratum corneum). You can see that in the image below.

Thus, retinoids make the cells believe it is a time of abundance: they stimulate epidermal cells to grow (and differentiate) in an enhanced yet organized manner. 

The accelerated growth and increased epidermal renewal are beneficial since they increase skin thickness and promote epidermal youth. Also, a faster elimination of cells that could have acquired DNA mutations (due to sunlight exposure, for instance) and, hence, could give rise to skin cancer.

But there’s a potential caveat here.

Can we continuously push through skin renewal without eliciting exhaustion?

As I said before, due to its protective function and need for constant renewal, the epidermis has an extensive stem cell pool that can undergo many cell duplications and yield plenty of new cells throughout our lifetime.

However, stem cells, like other types of cells, also age. Often through certain DNA modifications or epigenetic changes. Besides, we know that even skin stem cells (and not only those in less proliferative organs) can reach exhaustion.

After many divisions (duplications), they may not self-renew: they differentiate and die. Or enter a state of senescence, where they cannot divide anymore.

Indeed, there is proof that in the average human (who does not apply retinol regularly), the number of cutaneous stem cells diminishes with age: the older you get biologically, the less potential for self-renewal and wound healing your skin has.

One could argue that regular use of topical retinoids may help retain a bigger pool of stem cells in the skin in the long run. They seem to do that. Nonetheless, we don’t know whether that happens when you apply retinoids without pause.

The higher the biological age of your skin, the lower its potential for self-renewal and wound healing.

There is the possibility that, eventually, the uninterrupted use of retinol for extended periods (aka, every day for many years) may lead to significant skin stem cell aging and exhaustion.

That would sooner or later precipitate a cutaneous decline. And compromise the skin barrier function and beauty. Even its ability to heal wounds.

How do we take advantage of the benefits of topical retinoids for life?

It is unclear whether the continuous application of retinoids might lead to skin stem cell exhaustion and accelerated skin aging later in life.

And you already get undoubted skin aging prevention (and even reversion) benefits by applying retinoids less often (not every day). 

Therefore, it may be better to take our long-term skin aging prevention or cutaneous rejuvenation approaches more gently. Do not step on the gas that much. And use retinoids more sparingly (for example, just one or a few times per week).

Even take a little “retinoid break” once in a while.

Otherwise, the skin behaves as if there was a perpetual period of abundance or growth (signaled by retinoids). Then, scarcity might hit (in some form of stem cell exhaustion). Next thing you know, your retinoids don’t work that well anymore, and skin troubles (such as accelerated aging) could begin.

That is a hypothesis. But there are reasons to believe that could occur. 

Applying retinoids less often, you might avoid significant stem cell exhaustion long-term while retaining an enhanced pool of skin stem cells (compared with someone who does not use topical retinoids regularly).

And most probably extend the benefits of topical retinoids (and a good-looking, healthy skin) for life.

How often do you apply retinoids?

Was this article of your interest?

Comment below! 

See you soon,

María

For your reference:

The hallmarks of aging. López-Otín C et al., Cell, 2013; 153(6): 1194-217.

Molecular mechanisms of retinoid actions in the skin. GJ Fisher and JJ Voorhees, FASEB J, 1996; 10(9): 1002-13.

Skin and its regenerative powers: an alliance between stem cells and their niche. KA Uy Gonzales and E Fuchs, Dev Cell, 2017; 43(4): 387-401.

Stem cell aging: mechanisms, regulators and therapeutic opportunities. J Oh et al., Nat Med, 2014; 20(8):870-80.

When stem cells grow old: phenotypes and mechanisms of stem cell aging. MB Schultz and DA Sinclair. Development, 2016; 143(1): 3-14.

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