The Hayflick Limit, Cellular Senescence, & Skin Aging
Welcome to The Alchemy of Things, a podcast diving deep into topics like skincare, holistic living, and the energy that connects us all. I'm your host, Brandy Searcy, founder & formulator at Rain Organica, where you'll find skincare you can take with you anywhere.
In today's inaugural episode, we're going deep into skin. This is really a foundational episode for future discussions around skincare. One of the reasons this is going to be fairly intense is because my guess is you've searched for answers elsewhere and haven't been able to find the full story. For that reason, I want to give you the entire story all in one location.
And, it's a little difficult to pull these apart and have a full podcast episode, so for that reason, this one's a little bit intense with a few heavy concepts, but don't worry, I'm here to guide you through it.
We'll start out talking about the layers of skin, from there, we'll talk about cellular migration, and then the Hayflick limit, and finally cellular senescence. So, let's get started.
The skin is composed of three layers, the epidermis, the dermis, and the subcutaneous fat layer. Today, we're focusing just on the epidermis, and this layer of skin is further divided into, you guessed it! Layers.
- outermost layer: stratum corneum the infamous dead skin layer that forms a barrier between our body and the world. The stratum corneum is made up of dead skin cells that are fully keratinized (sometimes called corneocytes) which are continuously resupplied by lower layers of the epidermis.
- second outermost layer: the stratum granulosum lies just underneath the stratum corneum and helps maintain an intact skin barrier by secreting lipids (fancy name for fats), which compose the extracellular matrix that help hold cells together. Cells in the stratum granulosum also secrete protens & enzymes that enable desquamation (the technical name for exfoliation) in the stratum corneum
second innermost layer: below the stratum granulosum is the stratum spinosum - this is the next to the bottom layer of the epidermis and is where keritinization aka cornification starts. The cell nucleus begins to deteriorate, and the cell membrane cross-linking of keratin proteins, which are rich in sulfur containing amino acids like cysteine, starts to take place.
Cross-linking is a chemical reaction where keratin proteins bind together at the sulfur containing amino acids to build a strong fiber that helps create skin's semi-permeable membrane.
- innermost layer: at the very bottom, the innermost layer (& the living layer) of the epidermis, we have the stratum basale layer, composed of:
- keratinocytes, which are the cells (& can also create the cells through cellular division) that migrate towards the surface becoming more and more keratinized or cornified throughout that migration
Keratinocytes are also capable of dividing to form other keratinocytes. This is true of most cells in your body. Most cells in your body can divide to produce other cells like it.
- epidermal stem cells, which create keratinocytes
- melanocytes, which create the pigment, melanin
- Merkel cells, which are responsible for detecting touch... think of when you rub your fingers across a sheet of paper and then when you rub your fingers across a soft blanket. The Merkel cells help translate that sense of touch to your brain.
A note about melanin
Melanocyte density is about the same regardless of skin color, & the difference in skin color is due to the amount of melanin made by those melanocytes.
So, when you have a suntan, your melanocytes make more melanin than when you don't have a suntan, and if you have a darker complexion, your melanocytes are just making more melanin than somebody with a lighter skin color.
(We'll talk about freckles and age spots in a later episode, and both of these have to do with melanocytes in your skin.)
Melanin is a highly protective antioxidant, one that's made naturally by the body, and we'll talk more about antioxidants in episode 3.
Melanocytes and epidermal stem cells each compose about 5 to 10% of the total population of skin cells in the stratum basale (living layer of the epidermis).
Now let's talk about cellular turnover aka cellular migration.
Cellular turnover from the stratum basale to the top layer of the stratum corneum varies based on the thickness of skin in a particular area (think of the inside of your wrist compared with the thickness of skin on the palm of your hands and soles of your feet), your age, and also whether you have skin conditions (psoriasis and other skin conditions exhibit faster or slower turnover rates).
A general rule of thumb is a 28-day turnover time for a skin cell to migrate from the stratum basale all the way to the top of the stratum corneum and to be shed from the stratum corneum, and this increases between 30 and 50% by age 80.
So, at age 80, it could take as long as 42-days for a skin cell to migrate, again, this is based on which area of the body we're talking about and a number of other factors like photoaging.
You may have heard of the Hayflick limit before, but let's go ahead and introduce it here, just in case.
Let's go back in time to high school biology.
DNA is a double-stranded sequence of nucleotides that code for your genes, and your DNA is in every living cell of your body.
During cellular division, the enzyme, DNA polymerase, breaks open the double-strand of DNA, attaches itself to the 3-prime end, copies the strand of DNA, and then disconnects from the DNA strand.
Since DNA is double-stranded and polymerase is an enzyme (so it's very large compared to a nucleotide within the DNA strand), polymerase can't really copy the nucleotide sequence at the ends of the DNA strand very well.
And, that's simply because it has to disconnect the double strand, physically attach itself to the strand, and since the enzyme is so large, the portion of the enzyme responsible for making that connection and the part of the enzyme responsible for copying the nucleotide sequence just doesn't fit well at the ends of the DNA strand itself, so the very end of the DNA sequence gets clipped with each cellular division.
For this reason, the body has a workaround. On the end of DNA strands, additional repeating sequence of nucleotides are added as an end cap onto the DNA strand. If you're curious, in humans and other vetebrates, this oligonucleotide sequence is TTAGGG, and the additional non-sensical sequence (doesn't code for a gene) is known as a telomere, and that entire telomere portion tacked onto the DNA strand is about 8,000 to 10,000 nucleotides long.
So, what does that mean?
This ties into how well, or rather how long, or how many times a cell is able to be replicated. A cell will naturally reach the end of its lifespan when those telomere lengths become so short that DNA polymerase cannot physically attach itself onto the DNA strand and be able to read the entire DNA strand that codes for your genes.
When the cell has replicated to this point, the cell should enter a natural state of programmed cell death known as apoptosis and is then cleared from the body, so it dies, is broken down, and then the cellular debris is removed from the body.
Natural cell death gone awry... cellular senescence
What can happen instead of cellular apoptosis is the cell enters a state of senescence. I used to think of senescence as a sleep state, but it's not, it's actually... well, let me describe it and see what you think is the best explanation for this.
Senescent cells are cells that:
- can no longer replicate because their telomere lengths are too short
- resist natural programmed cell death (aka apoptosis)
- and they also secrete high levels of inflammatory signalling molecules
These signalling molecules cause nearby cells to enter a state of senescence as well, so that those nearby cells (regardless of their age) stop dividing, avoid apoptosis, and begin secreting high levels of inflammatory signalling molecules.
That sounds like a bad thing, right? Yes, sounds kind of like a chain reaction.
There are all sorts of theories regarding senescence and aging. And, it's not just skin cells that can enter this state of senescence (even though we're limiting this particular conversation to skin cells). Senescence can happen throughout the body, and this is a particularly hot topic for research.
About the Author
Brandy's a formulation scientist and self-proclaimed health geek who loves hiking, gardening, bird-watching, and body boarding.
Her struggle with acne during her teens and 20s led to a holistic and healthy approach to skincare, embracing skin as an organ to be loved and cared for rather than a canvas to wage war on.
Since 2008, she's been developing all-in-one products for a simple routine at home, & Rain Organica started when her backpacking friends asked for a portable skincare routine to keep their skin healthy & happy on and off the trails.
You can try Rain Organica for yourself with The Essentials Kit, a complete skincare routine in just 3 steps.
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