February 26, 2016

Breakthrough in understanding human skin cells paves the way for effective drugs for youthful skin

For the first time, scientists at Newcastle University have identified that the activity of a key metabolic enzyme found in the batteries of human skin cells declines with age.

A study, published online in the Journal of Investigative Dermatology, has found that the activity of mitochondrial complex II significantly decreases in older skin.

This discovery brings experts a step closer to developing powerful anti-aging treatments and cosmetic products which may be tailored to counteract the decline in the enzyme’s activity levels.



Journal of Investigative Dermatology - Age-Dependent Decrease of Mitochondrial Complex II Activity in Human Skin Fibroblasts



Paving the way for drug developments

Findings may also lead to a greater understanding of how other organs in the body age, which could pave the way for drug developments in a number of age-related diseases, including cancer.

Mark Birch-Machin, Professor of Molecular Dermatology at Newcastle University, led the pioneering study with Dr Amy Bowman from his research group.

Professor Birch-Machin said: “As our bodies age we see that the batteries in our cells run down, known as decreased bio-energy, and harmful free radicals increase.

“This process is easily seen in our skin as increased fine lines, wrinkles and sagging appears. You know the story, or at least your mirror does first thing in the morning!

“Our study shows, for the first time, in human skin that with increasing age there is a specific decrease in the activity of a key metabolic enzyme found in the batteries of the skin cells.

“This enzyme is the hinge between the two important ways of making energy in our cells and a decrease in its activity contributes to decreased bio-energy in aging skin.

“Our research means that we now have a specific biomarker, or a target, for developing and screening anti-aging treatments and cosmetic creams that may counter this decline in bio-energy.

“There is now a possibility of finding anti-aging treatments which can be tailored to differently aged and differently pigmented skin, and with the additional possibility to address the aging process elsewhere in our bodies.”

Enzyme activity declines with age

Complex II activity was measured in 27 donors, from aged six to 72 years. Samples were taken from a sun-protected area of skin to determine if there was a difference in activity with increasing age.

Techniques were used to measure the activities of the key enzymes within mitochondria that are involved in producing the skin cell’s energy, a type of mitochondrial gym or skin physical. This was applied to cells derived from the upper (epidermis) and lower (dermis) levels of skin.

It was found that complex II activity significantly declined with age, per unit of mitochondria, in the cells derived from the lower rather than the upper levels, an observation not previously reported for human skin.

The scientists found that the reason for this is the amount of enzyme protein was decreased and furthermore this decrease was only observed in those cells that had stopped proliferating.

Further studies will now be required to fully understand the functional consequences in skin and other tissues, and to establish methods to assess anti-ageing strategies in human skin.

Dr Bowman, Research Associate at Newcastle University’s Institute of Cellular Medicine, said: “Newcastle University is pioneering research into aging as it has long been thought that mitochondria play an important role in the aging process, however the exact role has remained unclear.

“Our work brings us one step closer to understanding how these vital cell structures may be contributing to human aging, with the hope of eventually specifically targeting areas of the mitochondria in an attempt to counteract the signs of aging.”

A recent study carried out in mice showed that complex II activity is lower in the skin of naturally aged older mice compared to younger mice.

Abstract

The mitochondrial theory of aging remains one of the most widely accepted aging theories and implicates mitochondrial electron transport chain dysfunction with subsequent increasing free radical generation. Recently, complex II of the electron transport chain appears to be more important than previously thought in this process, suggested predominantly by nonhuman studies. We investigated the relationship between complex II and aging using human skin as a model tissue. The rate of complex II activity per unit of mitochondria was determined in fibroblasts and keratinocytes cultured from skin covering a wide age range. Complex II activity significantly decreased with age in fibroblasts (P = 0.015) but not in keratinocytes. This was associated with a significant decline in transcript expression (P = 0.008 and P = 0.001) and protein levels (P = 0.0006 and P = 0.005) of the succinate dehydrogenase complex subunit A and subunit B catalytic subunits of complex II, respectively. In addition, there was a significant decrease in complex II activity with age (P = 0.029) that was specific to senescent skin cells. There was no decrease in complex IV activity with increasing age, suggesting possible locality to complex II.

SOURCeS - Newcastle University, Journal of Investigative Dermatology

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