Aging through the decades

Maritza Perez, M.D.

Dermatologists have always known that different ethnic skin types age at different rates, but until now there hasn’t been clear evidence that these phenotypic differences have a pathophysiologic and histologic basis. Maritza Perez, M.D., Icahn School of Medicine at Mount Sinai, New York, presented new research illustrating the aging process across the decades and how it differs between ethnic skin types.

The objective of the study was to develop a fundamental understanding of the molecular mechanisms which contribute to skin aging, both intrinsic and extrinsic, across different ages, body sites and ethnicities. It is hoped that a greater understanding of the process will highlight potential interventions that could slow or prevent the aging process, or even reverse it.

The study included around 25 women in each of five decades of life, from their 20s to their 70s, from each of four ethnic groups:  Caucasian, Hispanic, Chinese and African-American. The ethnic backgrounds of participants were confirmed by genetic analysis. Skin biopsies were taken of the scalp, the face, the dorsum of the arms and the buttocks for analysis; the biopsy from the buttocks represented the intrinsic ageing process, where sun exposure is not implicated, and the other samples, extrinsic ageng, where the ageing process is accelerated by sun exposure.

Examination of the samples revealed that elastosis was evident in some sun exposed areas and increased with advancing age; it started in the 40s for Caucasian skin, and two decades later (60s) for Chinese and Hispanic skin. However, there was no evidence of the elastosis during any decade for the African Americans.

“Elastosis is directly proportional to the appearance of youth,” Perez explains. “If you have elastosis you have crinkly skin, and if you don’t have elastosis you look younger.”

Computer analysis of the valleys and hills of the skin of the faces of participants revealed that a 64-year-old woman of African descent had a similar appearance to that of a Caucasian aged 54, ie the African American looked 10 years younger.

Histological examination highlighted differences in epidermal thickening according to ethnic skin type; the Hispanics began showing a decrease in epidermal thickening in their 40s, the Caucasians in their 50s, and the Chinese in their 60s. The only group not to show a decrease in epidermal thickening at any age were the African-Americans. Similarly the stratum corneum of Caucasians, showed thickening from the 40s, which increased with age, but no thickening was evident in the skin of African-Americans.

THE STUDY

Using transcriptomic profiles the researchers then look at the differences in protein production in the skin of different ethnic groups at different ages, to see if their were differences at a molecular level. 

In general, from the 20s, there is a decrease in the pathways and metabolisms related to natural antioxidants, indicated by a fall in glutamylcysteine synthetase, which is a marker for antioxidant.

In the 30s there is a decline in expression of the genes for energy storage (mitochondrial structure and function) - nicotinamide adenine dinucleotide (NAD).

Using a laser to separate the dermis from the epidermis, it was possible to look in more depth at what was happening in separate parts of the skin structure. This revealed that senescence expression increases with age from the 40s, particularly in the epidermis but also in the dermis, and is more evident in sun exposed areas of the skin.

Pathways and metabolism related to the production of skin barrier building blocks (lamellar body formation) start to decline in the 50s. “When you have a healthy epidermis, you have a healthy barrier and your moisture is controlled, it doesn’t leave the body,” explains Perez. “In the fifth decade you are losing the function of the barrier so now you see that there is less holding of the moisture inside and the skin gets dry and cracked. It happens both in the photo exposed and the photo protected areas, so it is a kind of intrinsic pathway.”

AGING POST MENOPAUSE

Following the menopause, so in the 60s and 70s, ageing occurs 6.79 times faster due to downregulation of genes.

AGING AND ETHNIC GROUPS

In terms of differences between the ethnic groups at the molecular level, the transcriptomic profile of the skin of a photo-exposed arm of a 50-year-old Caucasian is comparable to the transcriptomic profile of a 60-year-old African-American, which basically proves molecularly that African-Americans are ageing more slowly, Perez says. “This is the only process that has been totally analysed, it is a work in progress,” she adds.

Senescence gene expression only remains stable in the areas of Caucasian skin protected from the sun (buttocks), while in sun exposed areas expression accelerates significantly with age. However, in African-Americans, senescence gene expression remains relatively stable across all skin areas.  Also when senescence gene expression was compared according to participants’ liking of being in the sun, those who loved the sun had more marked expression of senescence genes than people who protected themselves from it.

AGING AT DIFFEREINT RATES

Not all Caucasians, Hispanics and Chinese age at the same rate, just under one in ten are known as exceptional skin agers, meaning that they age more slowly. In this group, only about half of the over 2100 genes associated with youthful appearance overlapped with genes associated with age in epidermal samples. This group also had a unique gene expression fingerprint, when compared with others of their age, and gene analysis suggests that genes expression for the barrier repair processes is preserved for longer: expression of 18 energy genes, 40 barrier genes and lamellar was mainly preserved, while they were under-expressed older looking women of the same age.

OLIVE OIL?

The study, which was funded and conducted by Procter and Gamble, showed that Pal-KTTKS and olive oil derivative can induce the expression of energy and barrier genes, and Pal-KTTKS can also induce expression of anti-aging genes. Exceptional agers reported being more likely to protect themselves from the sun and two particular small nuclear peptides -  rs12203592 and rs4268748 – were exceptionally present in samples of their skin.

Finally, microbiome analysis compared Caucasians and African-American skin. Swabs of the buttocks and arms indicated that both races have similar types of bacteria -  on the buttocks it is Corynebacterium, and on the arms it is Staphylococcus. Both races had Propionibacterium on the face, but different types. “What does that means we do not know,” admits Perez.

She concludes: “There are similarities and differences in skin aging across ethnicities which might help to develop more tailored approaches to anti-aging solutions.”

References:

“The Evaluation of the Aging Process Across Ethnic Variations,” Maritza Perez, M.D. Skin of Colour Seminar Series. 5-6 May, New York. May 5, 2018