Cell division and skin

The human body consists of different types of cells, such as muscle cells, nerve cells and skin cells. They renew themselves at different intervals. Daily cell renewal depends on the number of cells and their lifespan. The average man between the ages of 20 and 30, weighing 70 kg and standing 1.70 m tall, has a total turnover of 330 ± 20 billion cell renewals per day in a healthy state. The majority of these are the rapidly dividing blood and intestinal cells. Skin cells reorganize more slowly. [1] Cell division occurs in the stratum basale of the epidermis. The cycle of cell renewal here takes about 4 weeks. [2] In terms of mass, a total of 80 ± 20 g of new cellular material is produced in the body every day. [1]

Cell division

In cell division (cytokinesis), the mother cell divides by mitosis into one or more daughter cells whose genome (genetic material) is identical. The situation is different in meiosis, sexual reproduction within a species, which combines two different genomes into a new common one. Disturbances in cell division manifest themselves in uncontrolled cell growth or tumor formation, among other things. [3, 4]

Eukaryotic mitosis

In contrast to the prokaryotic, i.e. nucleus-less cells (ancient Greek: pro = before and karyon = nucleus) of bacteria and archaea (unicellular organisms), the eukaryotic cells (ancient Greek: eu = right and karyon = nucleus) of humans, animals, plants and fungi have a cell nucleus in which the majority of the cellular genetic material is deposited in the form of chromosomes. Chromosomes consist of double-helically coiled nucleotides – known as DNA (deoxyribonucleic acid) [5] Mitosis passes through various phases in which the X-shaped chromosomes located in the cell nucleus duplicate. At the end of this complex process, two cells with identical genetic material are present. [3]

Telomeres

At the ends of the chromosomes are the telomeres (Greek: télos = end and méros = part), which are responsible for the stability and protection of the DNA. Like DNA, they consist of nucleotide sequences, but do not contain any relevant genetic information. With each cell replication they become shorter until they are used up. The cell can then no longer divide and ceases to function. In stem cells or even cancer cells, high activity of the enzyme telomerase ensures the constant lengthening of telomeres so that the cells can continue to proliferate. [3, 6]

Replicative senescence

Cells whose telomeres are not renewed due to a lack of telomerase activity can only carry out a certain number of cell divisions. This phenomenon is called replicative senescence (Latin senescere = to age). [7] In the optimal case, the cell enters the so-called "crisis" state at a certain telomere length and initiates its apoptosis (programmed cell death). Macrophages (scavenger cells) break down the cell remnants. [3] However, there are cells that can suppress apoptosis. They are still metabolically active, but unable to divide. These cells, whose function is restricted, remain in the tissue and secrete pro-inflammatory substances into their environment. These cells are assigned to the senescence-associated secretory phenotype (SASP). They are capable of causing neighbouring cells to age as well. The immune system can kill senescent cells. They accumulate in diseased and ageing tissue. [8, 9]

Skin and telomeres

So far, it is not known what role the shortening of telomeres plays in skin aging. In dyskeratosis congenita, a hereditary disease affecting many organs with characteristic skin involvement, shortened telomeres could be found. Sufferers frequently show nail dystrophy, premature greying of the hair, hair loss and colour changes of the skin. From this it was deduced that the preservation of telomere length is the prerequisite for healthy skin balance with its functions. [10]
The sensitivity of telomeres to oxidative stress was also confirmed. A human fibroblast culture exposed to hyperoxic stress (excess oxygen) showed the same shortening of telomere length as demonstrated in senescent fibroblasts. [7]

Cellular skin aging

The proinflammatory messenger substances of the senescent cells may produce inflammatory efflorescences. The dermoepidermal junction (DEJ) lying between the epidermis and dermis flattens. In youth, it prevents detachment of the epidermis by its sawtooth-like composite of rete ridges and anchoring fibrils. In old age, it is mechanically more vulnerable. [11]
The new cell formation of the skin slows down, which results in a longer lasting wound healing in case of injuries. [12]
The intercellular lipid composition changes. Compared to the youthful skin, the lipid content in the aged stratum corneum is reduced by more than 30%. A constant ratio of cholesterol, free fatty acids and ceramides is necessary for an intact skin barrier. [13]
The natural moisturizing factor of the skin (NMF) decreases due to the reduced synthesis of profilaggrin [11, 14, 15] as the amino acids of NMF result from the degradation of profilaggrin. Together with urea and other substances they bind the moisture in the stratum corneum.

Summary and outlook

The length of telomeres is the marker for the biological age of cells. Cellular senescence and apoptosis are tumor suppressive protective measures of the cell. The replication of gene-defective cells is prevented. The number of senescent cells successively increases in the tissues.
Research is currently looking at the possibility of using senolytics (Latin senescere = to age and Ancient Greek lysis = to dissolve) to remove senescent cells from tissues and reduce the associated inflammatory factors. [16]
Another goal could be to lengthen telomeres by activating telomerase. However, there is a risk that this non-specific approach may also promote the growth of precancerous cells. [17, 18]

Literature

1. R. Sender, R. Milo, Nature Medicine 2021 (27), 45-48
2. I. Moll, Dermatologie, Georg Thieme Verlag, Stuttgart 2005, ISBN 978-3131266866
3. W. Janning, E. Knust, Genetik: Allgemeine Genetik – Molekulare Genetik – Entwicklungsgenetik, Georg Thieme Verlag, Stuttgart 2004, ISBN 978-3131287717
4. Bundesministerium für Bildung und Forschung (BMBF), Referat für Gesundheitsforschung, Zellen außer Kontrolle – Erkenntnisse aus der Krebsforschung 2012, 11-12
5. A. L. Lehninger, D. L. Nelson, M. M. Cox, Prinzipien der Biochemie, Spektrum Akademischer Verlag, Heidelberg-Berlin-Oxford 1994, ISBN 978-3860251065
6. C. López-Otín et al., Cell 2013, 153 (6), 1194-1217
7. G. Saretzki, T. von Zglinicki, Zeitschrift für Gerontologie und Geriatrie 1999 (32), 69-758.
8. M. Scudellari, Nature 2017 (550), 448-450
9. B. G. Childs et al., EMBO reports 2014, 15 (11), 1139-1153
10. E. M. Buckingham, A. J. Klingelhutz, Experimental Dermatology 2011, 20, 297-302
11. P. Fritsch, Dermatologie und Venerologie: Lehrbuch und Atlas, Springer-Verlag, Berlin 2013, ISBN 978-3662217719
12. E. Proksch, Zeitschrift für Gerontologie und Geriatrie 2015 (4), 1-7
13. Z. Wang et al., Aging 2020, 12 (6), 5551-5565
14. C. Bayerl, Pharmazeutische Zeitung 2017 (32), online
15. A. V. Rawlings, C. R. Harding, Dermatologic Therapy 2004, 17, 43-48
16. E. Dolgin, Nature Biotechnology 2020 (38), 1371-1377
17. M. A. Shammas, Current Opinion in Clinical Nutrition and Metabolic Care 2011, 14 (1), 28-34
18. C. Eissenberg, Missouri Medicine 2013, 110 (1), 11-16

 
Anne Schieferecke