Aging is an accumulation of specific forms of cell and tissue damage, coupled with the dysfunctions produced by that damage. While the damage of aging would occur regardless of the surrounding environment, many environmental exposures also produce cell and tissue damage. This additional burden of damage can result in what appears to be accelerated aging, even if the damage is somewhat dissimilar in character to that produced during aging by the body itself. Sometimes the damage is in fact similar. Photoaging of skin resulting from ultraviolet light exposure is a good example; like any radiation exposure, this causes a greater burden of some of the forms of damage and dysfunction known to occur with age, such as DNA damage and an increased burden of senescent cells.
One way to reduce the impact of aging is to increase the activity of cellular maintenance processes. Many of the interventions show to slow aging in animal studies involve upregulation of autophagy, for example, a way for cells to remove damaged components in order to better resist damage-induced dysfunction. When most of the cells in the body are more aggressively maintained, age-related declines in tissue function are slowed. In today's open access paper, researchers show that this sort of approach also reduces the impact of photoaging. One of the targets of autophagy is damaged mitochondria in the cell, and this specific form of autophagy is called mitophagy. Since there are hundreds of mitochondria in every cell, and only some of them are at any given time rendered damaged and dysfunctional by radiation exposure, more aggressive clearance of those damaged mitochondria via mitophagy helps to reduce consequent impairment of tissue function.
Various factors contribute to skin aging, which can be categorized into internal and external factors. External factors include air pollution, ultraviolet (UV) radiation, lack of sleep, and smoking. UV radiation, in particular, causes photoaging. Repeated exposure to UV, especially UVB radiation, generates reactive oxygen species (ROS), which accelerate the breakdown of collagen and elastin by upregulating matrix metalloproteinases (MMPs), leading to photoaging symptoms such as wrinkles, dryness, loss of elasticity, and pigmentation.
Current treatments for skin photoaging include photodynamic therapy, oral and topical drugs, and stem cell therapies. Human adipose-derived stem cells (hADSCs) are a type of mesenchymal stem cell with self-renewal and multidifferentiation abilities, as well as immunomodulatory effects. Exosomes are extracellular vesicles, ranging from 30 to 200 nm, formed through endocytosis, fusion, and exocytosis. These vesicles are rich in nucleic acids, proteins, cytokines, and other bioactive compounds. As a promising alternative to stem cells, exosomes eliminate the risk of immune rejection associated with stem cell transplants, offering an effective, non-invasive option for anti-aging therapies. This has led to increasing interest in their potential for skin rejuvenation.
Research has shown that photoaged skin exhibits a tenfold increase in mitochondrial DNA (mtDNA) common deletion compared to sun-protected skin in the same individual. Preserving mtDNA integrity is critical for mitochondrial function. Accumulation of mutations can impair mitochondrial subunits, increasing ROS production and perpetuating oxidative damage within mitochondria. However, mtDNA has limited repair capacity, making the clearance of damaged mtDNA via mitophagy essential for reducing oxidative stress in cells. Mitophagy is a crucial process that regulates mitochondrial quality and quantity in eukaryotic cells, selectively eliminating damaged or dysfunctional mitochondria. The PINK1/Parkin pathway is a well-established mediator of mitophagy.
This study aimed to explore the role and mechanism of hADSC-derived exosomes (hADSC-Exos) in addressing skin photoaging. hADSC-Exos were isolated, and their surface markers were identified. Human dermal fibroblasts (HDFs) and nude mice were exposed to UVB irradiation, and treated with hADSC-Exos. Oxidative stress, senescent cell burden, and photoaging were assessed. In UVB-exposed HDFs and nude mice, the number of SA-β-gal-positive cells, along with levels of p21, ROS, and mtDNA deletion, were significantly increased, but these effects were reduced by hADSC-Exos. Moreover, hADSC-Exos treatment significantly elevated PINK1 and Parkin levels. In conclusion, hADSC-Exos can mitigate skin photoaging by promoting PINK1/Parkin-mediated mitophagy, thereby reducing mtDNA deletion and oxidative stress.
View the full article at FightAging
