The Pathology of Photoaging

The Macro Pathology

Actinic (or solar) damage, typically referred to as photoaging, is caused by excessive exposure to non-ionizing ultraviolet (UV) radiation in the wavelengths of 315-400nm (UVA) and 280-315nm (UVB). Thankfully, the extremely damaging UVC radiation is completely absorbed by the Earth’s atmosphere (see the following Electromagnetic Spectrum diagram).

electromagnetic spectrum diagram

However, the wavelengths of UVA and UVB are not absorbed in the epidermis of human skin but rather penetrate through it and damage the underlying papillary dermis. The microscopic description of this damage is basophilic degeneration. It can be seen clearly in the blue staining on H&E biopsy slide micrographs (see illustration from the 283 person study). This structural and functional deterioration results in many types of skin changes, including epidermal and dermal atrophy with sebaceous and eccrine gland loss, rhytids (wrinkles), squamous cell carcinomas, basal cell carcinomas, actinic keratoses, ventigos, pigmentary changes (hypopigmentation and hyperpigmentation), “rosacea”, milial cysts, ecchymoses, and skin tears.

Starting at approximately 30 years of age, the combination of photodamage and aging causes a loss of collagen (at a rate of 2-3% per year), elastin and hyaluronic acid.  This results in an increasing diminishment of skin strength, elasticity and volume. There are also similar losses of capillaries and fibrocytes which nourish, grow, and maintain the skin. This damage and aging also effaces the interdigitation between the epidermal rete ridges and the dermal papillae (see below biopsy photos), causing the atrophic skin to separate between the basement membrane and the papillary dermis – with a resulting increase in the frequency of skin tears, ecchymoses, and abrasions.

2mm punch biopsy

The Cellular Pathology

On an electron microscopic level, when skin is exposed to UV-A and UV-B radiation, organelles within the keratinocytes – known as melanosomes – release a group of pigment (melanins) to surround and protect the nucleus.1,2 These melanins have two main variants: eumelanin, which consists of black and brown pigment, and pheomelanin, which consists of yellow and red pigments. Thus, people with darker skin tones have a higher concentration of eumelanin, while those with  lighter skin have a higher concentration of pheomelanin.

When UV radiation penetrates into the cell, there are two main mechanisms that cause damage to DNA, collagen, elastin and hyaluronic acid. The first is a pericyclic reaction – T-dimerization – between two adjacent pyrimidine nucleotides. The second is the creation of unstable reactive oxygen species (ROS) – hydroxyl or “free” radicals – that can react with various parts of the DNA.3,4 These reactions can cause nicks or bends in the DNA (mutations) that are typically repaired during nucleoside excision repair. However, if these mutations are not repaired, they become a permanent part of the genetic makeup of that cell and all further replications.5 Of course, with more photodamage there will be more mutations. These mutations in the basal cell layer lead to abnormal epidermal and dermal function including cancer formation. The free or hydroxyl radicals not only damage DNA, they also destroy extracellular material such as collagen, elastin and hyaluronic acid. This damage creates an inflammatory reaction which causes further destruction within the cells. The microscopic result of this upper dermal extracellular destruction is basophilic degeneration.

In people with lighter skin tones, these ROS cause individuals to be much more sensitive to UV radiation than those with darker skin tones. While most humans produce the same amount of melanins and have the same number of melanosome-producing melanocytes, variation in skin color is generally determined by the production of melanosomes as well as the type of melanin produced. Those with light skin tones almost solely produce pheomelanin and have fewer melanosomes in their keratinocytes. Ironically, a disadvantage of pheomelanin is that it is phototoxic and produces more ROS, which produces even more damage to DNA.

On the other hand, eumelanin absorbs the energy of UV radiation. Rather than producing hydroxyl radicals, it quickly dissipates the ultraviolet energy as heat. However, even individuals with eumelanin-rich skin will still suffer actinic damage. Thus, protection from UV radiation will minimize these issues.

Future Science Commentary Articles will include discussions of photoaging damage as it relates to sun screens, the four types of rhytids (wrinkles), basal cell carcinoma, squamous cell carcinoma, melanoma, actinic keratoses, ecchymosis, skin tears, pigmentary alterations, “rosacea”, and milial cysts.

References

  1. Raposo G, Marks MS. Melanosomes – dark organelles enlighten endosomal membrane transport. Nat Rev Mol Cell Biol. 2007;8(10):786-797. doi:10.1038/nrm2258
  2. Ando H, Niki Y, Ito M, et al. Melanosomes Are Transferred from Melanocytes to Keratinocytes through the Processes of Packaging, Release, Uptake, and Dispersion. J Invest Dermatol. 2012;132(4):1222-1229. doi:10.1038/jid.2011.413
  3. Hydroxyl Radical – an overview | ScienceDirect Topics. Accessed September 9, 2022. https://www.sciencedirect.com/topics/chemistry/hydroxyl-radical
  4. How Ultraviolet Light Reacts in Cells | SciBytes | Learn Science at Scitable. Accessed September 9, 2022. https://www.nature.com/scitable/blog/scibytes/how_ultraviolet_light_reacts_in/
  5. Le May N, Egly JM, Coin F. True Lies: The Double Life of the Nucleotide Excision Repair Factors in Transcription and DNA Repair. J Nucleic Acids. 2010;2010:616342. doi:10.4061/2010/616342
  6. Taylor SC, Kelly AP, Lim HW, Anido Serrano AM, eds. Taylor and Kelly’s Dermatology for Skin of Color. Second edition. McGraw-Hill Education; 2016.
  7. Tanaka H, Yamashita Y, Umezawa K, Hirobe T, Ito S, Wakamatsu K. The Pro-Oxidant Activity of Pheomelanin is Significantly Enhanced by UVA Irradiation: Benzothiazole Moieties Are More Reactive than Benzothiazine Moieties. Int J Mol Sci. 2018;19(10):2889. doi:10.3390/ijms19102889
  8. Research C for DE and. Sun Protection Factor (SPF). FDA. Published online November 3, 2018. Accessed September 9, 2022. https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/sun-protection-factor-spf
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