For the first time, scientists at Newcastle University have identified that the activity of a specific and 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 senescent older skin cells. It adds further evidence that senescent cells are thought to play a prominent role in the aging process, potentially via mitochondrial dysfunction and finding a method for removal of them to be an anti-aging measure.
It was also found that the age-related decline in complex II activity in the skin is specific to fibroblasts, as a decline was not observed in keratinocytes. It was speculated that this was because the epidermal skin cells were being replaced on a regular basis as a result of normal skin turnover.
In addition the activity of complex II was examined in senescent and nonsenescent skin fibroblast cell populations, as senescent cells are thought to play a prominent role in the aging process, potentially via mitochondrial dysfunction. This study demonstrated that complex II activity decreases in an age-dependent manner in FACS-sorted senescent cells but not in FACS-sorted nonsenescent cells. This could suggest that the overall decrease in complex II activity observed in skin fibroblasts with age demonstrated in this study was due to the senescent cells only. Work investigating the differences in mitochondrial complex activity between senescent cells from older and senescent cells from younger individuals has not been previously reported. This study provides evidence that senescent cells from older individuals are less efficient in terms of mitochondrial complex II activity than senescent cells from younger individuals, which could have implications in terms of deciphering the causes of the overall decrease in cellular efficiency observed with age. Higher levels of ROS generation are present in senescent compared to nonsenescent cells (Passos et al., 2007), potentially resulting in increased mitochondrial DNA and nuclear DNA damage and mitochondrial dysfunction (Passos et al., 2007) and a possible decrease in complex II activity if damage becomes sufficiently high. Damage to senescent cells may be higher in the skin of older individuals because of the lower levels of antioxidants observed with age (Micallef et al., 2007), as well as the age-related decline of senescent cell removal systems such as the immune system (Rodier and Campisi, 2011) and the autophagy/lysosomal pathway (Dutta et al., 2012). These factors could result in lower complex II activity in senescent cells of older individuals. In conclusion, the rate of complex II activity within human skin fibroblasts was shown to be lower in older individuals in this study, specifically in their senescent cells. It is likely that a decrease in complex II activity, whether causal or consequential in terms of the aging process, is likely to be exacerbating mitochondrial dysfunction with age.
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: “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”
The study came to its findings by measuring Complex II activity 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.