• General Dermatology
  • Eczema
  • Chronic Hand Eczema
  • Alopecia
  • Aesthetics
  • Vitiligo
  • COVID-19
  • Actinic Keratosis
  • Precision Medicine and Biologics
  • Rare Disease
  • Wound Care
  • Rosacea
  • Psoriasis
  • Psoriatic Arthritis
  • Atopic Dermatitis
  • Melasma
  • NP and PA
  • Skin Cancer
  • Hidradenitis Suppurativa
  • Drug Watch
  • Pigmentary Disorders
  • Acne
  • Pediatric Dermatology
  • Practice Management
  • Prurigo Nodularis
  • Buy-and-Bill

Article

Roles of p53 gene in photodamage, diabetes in intrinsic aging, warrant more study

The p53 gene is very important in dermatology for the prevention of skin cancer. P53 is the gene that is activated when viable epidermal skin cells are damaged by UV radiation. UV radiation strikes the skin and is first transformed to heat by an organic sunscreen and possibly reflected by an inorganic sunscreen. If the sunscreen fails to diffuse all of the damaging UV radiation, keratinocytes function to reflect and scatter the radiation.

Key Points

Q. What is p53?

If UVA continues to penetrate the skin, eventually it produces highly reactive oxygen species that reach the melanocyte with its protective melanin cap. The melanin serves to donate an electron to the reactive oxygen species, causing the melanin to oxidize and undergo a color change commonly referred to as tanning.

Failure of the p53 gene to function properly results in photoaging and skin cancer, more commonly seen in Fitzpatrick skin types I and II, where the DNA protection by the melanin cap is deficient. It is theorized that many of the changes associated with an aged appearance are due to improper repair of UV-induced DNA damage that is cumulative over the life of the individual. Skin cancer results from faulty DNA repair in cells that probably should have undergone apoptosis, but were not destroyed.

It is apparent that modulation of p53 is important in preventing skin cancer and even aging, if we believe that aging is a state that precedes precancerous skin changes on a continuum to cancer. These changes can be observed in the skin more readily than any other body organ, but it is likely these same genetic abnormalities account for aging in other organs as well.

Q. What is the relationship between diabetes and premature skin aging?

A. The effects of UV-extrinsic aging on the skin are well understood, but understandings of the effects of intrinsic aging on the skin are not as well documented. Part of the problem in studying intrinsic skin aging is identifying a human model for evaluation, yet we observe that some people have more attractive skin than others, despite the same amount of photo exposure.

One such model that may be valuable to study factors important in intrinsic aging is diabetes. Because of higher-than-normal circulating glucose levels, diabetics exhibit more protein glycation than their age-matched nondiabetic counterparts. Protein glycation occurs when circulating glucose binds to the proteins that are ubiquitous in the body to include skin, nerve and muscle. It is the binding of sugar to skin protein that results in the decreased elasticity of diabetic skin and accompanying poor wound healing. Glycation of nerves leads to diabetic neuropathy, and glycation of heart muscle leads to a decreased ejection fraction.

One of the changes that occurs with intrinsic aging is glycation in all persons, but at a more accelerated rate in diabetics. These changes can be easily studied in the skin because the glycated proteins fluoresce under a Wood's light. Currently, skincare products are being sold that claim to inhibit protein glycation in the skin as a new anti-aging target. Indeed, skin glycation should be minimized to have youthful skin, but how much glycation can be inhibited topically is unknown.

It is also unclear how tightly glucose must be regulated to prevent premature skin glycation, but endocrinologists are now aggressively treating mature persons who have a fasting glucose of 90 or above, as it is clear that the prediabetic state may be problematic.

Zoe Diana Draelos, M.D., is a Dermatology Times editorial adviser and consulting professor of dermatology, Duke University School of Medicine, Durham, N.C. Questions may be submitted via email to zdraelos@northstate.net.

Related Videos
1 KOL is featured in this series.
1 KOL is featured in this series.
1 KOL is featured in this series.
3 experts are featured in this series.
1 KOL is featured in this series.
1 KOL is featured in this series.
1 KOL is featured in this series.
2 experts in this video
2 experts in this video
© 2024 MJH Life Sciences

All rights reserved.