Photoaging: Pathophysiology

00:01 Welcome. In this particular talk, we're going to be talking about how you recognize that I look old photo aging, the changes in the skin that occur with time, but predominantly because of the effects of ultraviolet damage to the skin.

00:19 So skin damage or premature aging, and it's not even premature at my age.

00:23 I've earned all these wrinkles and all the spots.

00:26 It's due to chronic ultraviolet exposure.

00:29 Some of the wrinkles, particularly wrinkles at the corners of the eyes, are due to robust and repetitive kind of muscle contractions, but a lot of the wrinkles that we see and recognize in older individuals is because of UV exposure to ultraviolet light.

00:45 And we'll talk a bit in the pathophysiology part of this talk why that happens.

00:51 So the clinical features of photoaging, besides the fine and coarse wrinkling also involve focal hyperpigmentation Spot so-called age spots or solar spots.

01:03 And on histology that we will see in a moment.

01:06 This is due to something called solar elastosis.

01:08 We're going to see an actual degeneration of the extracellular matrix in the dermis that causes that. So the epidemiology pretty easy.

01:20 Importantly, as we think about photoaging, for the most part it's a cosmetic concern.

01:26 People who look old don't want to look old.

01:30 Yes. It's also, however, a bit of a kind of a marker for people who are at risk for developing malignancy.

01:38 And when we talk about squamous cell carcinomas and basal cell carcinomas and melanomas, later on, those will also have the same ultraviolet exposure as an important risk factor. Okay. Fair skinned populations clearly will have a higher prevalence of detectable photoaging.

01:55 That's because they have less melanin.

01:59 Other factors? Yes, as you get older, you're going to have more aging related photoaging. You're going to be if you're male, then you're also going to have increased risk. That's probably because and I think this is changing, but probably because men are out in the sun more, more often and for more prolonged periods of time doing whatever it is that guys do outside than women who may also be more likely to apply various agents to prevent photoaging or provide makeup.

02:34 High sun exposure. Clearly that's the more sun, the more UV exposure you're getting and living in geographic locations with high sun radiation. So if you are watching me from Australia, yes, you're getting lots of that, particularly during the winter months.

02:49 If you were watching me from Norway, not so much.

02:53 The severity increases rapidly after age 30.

02:56 This is a combination of accumulated damage, but also the fact that we, as we age, don't have the same regenerative capacity that we had in our youth.

03:06 Just one of those facts of life.

03:08 The severity, as you've already seen in the previous slide, is going to be associated with light, skin color and the frequency of burns.

03:15 So if you had a lot of burns or continue to have a lot of burns because of sun exposure, you're much, much more likely to develop significant photoaging changes in the darker skin populations. Um, wrinkling in some of the other photo changing is going to be delayed and for a couple of decades at least, and the severity overall tends to be much less.

03:38 So the pathophysiology.

03:39 Why is this happening.

03:42 Let's talk about this. So chronic UV exposure is going to cause DNA damage to epidermis.

03:46 That's what it does. It actually breaks the double stranded helix of the epidermal cells.

03:51 And that damage leads to changes in their ability to produce a variety of factors.

03:57 Yes. The Yes, the epidermal cells make factors that are important.

04:00 It's also going to look at or inhibit and interfere with their ability to heal as a result of the chronic UV exposure.

04:08 There's also going to be increased formation of reactive oxygen species.

04:12 And Ross. Ross is a a frequent flier in a variety of inflammatory processes.

04:20 These two things in tandem will lead to loss of structural integrity of the underlying dermis of the extracellular matrix. How is that happening? Well, reactive oxygen species in particular are going to increase matrix metalloproteinase synthesis of those dermal cells.

04:38 The the connective tissue cells the fibroblasts etc.

04:41 that live in the dermis.

04:43 That's going to lead to less production of type one and type three collagen as well as increased degradation.

04:51 The reactive oxygen species, those are very pro-inflammatory increase cytokines such as interleukin one and tumor necrosis factor, etc. that will increase the inflammatory response to UV radiation.

05:03 In fact, when you get a burn, you go out in the sun turns red.

05:07 That's because you're increasing those pro-inflammatory cytokines, that kind of kind of a warm feeling that you feel in the evening after a day out at the beach is because of the production of cytokines IL one and TNF.

05:20 In particular, combination of the altered synthesis of of extracellular matrix and increased inflammation leads to the loss of the structural integrity of the extracellular matrix within the dermis.

05:35 And notably, we'll come back to this in other talks.

05:37 The same pathways increase the risk of UV associated skin malignancies.

05:43 Okay. Reactive oxygen species.

05:46 And the change in in damage to the epidermis because of the breakage of the double stranded DNA.