Mitochondria are effectively power plants, hundreds of these organelles per cell working to create the chemical energy store molecule adenosine triphosphate. Mitochondria are the descendants of ancient symbiotic bacteria, and retain many bacterial characteristics, including a small genome, the mitochondrial DNA, and the ability to replicate. Mitochondrial dysfunction is one of the paths by which cells can become senescent, entering a state of growth arrest while secreting an inflammatory set of signals, but mitochondria are in any case involved in the transition to senescence in response to other forms of damage or dysfunction. In youth, senescent cells are quickly destroyed by their own programmed cell death processes or by the immune system. In older people, these cells accumulate, contributing to tissue dysfunction and the chronic inflammation of age.
In today's open access paper, the authors propose treating skin aging by delivering whole mitochondria into senescent cells, thereby rescuing their function. In recent years, various approaches to introducing mitochondria into target cells have been demonstrated. It also appears to be the case that cells naturally transfer, eject, and ingest mitochondria under a range of circumstances. Is rescuing the usual forms of senescent cells found in old tissues a good idea, however? If cellular senescence is largely due to mitochondrial dysfunction, which it may be under some circumstances, then the proposal here isn't completely unreasonable. But cells become senescent for a variety of good reasons, including nuclear DNA damage that is potentially cancerous, and which can occur in skin as the result of exposure to UV radiation. Selectively destroying senescent cells in skin sounds like a safer approach than attempting to rehabilitate them.
For what it is worth, delivering functional and undamaged mitochondria appears best targeted to normal cells in the aging body, to boost their function in an environment of damaged and dysfunctional mitochondria. Indeed, that has been attempted. Mitochondrial function does decline with age in tissues throughout the body. Perhaps something should be done about that. While it is unclear as to whether newly introduced mitochondria would remain functional for long in the aged environment, the strategy sounds worth a try, given the evidence to date for it to enhance tissue function in the short term.
The perception of mitochondria as only the powerhouse of the cell has dramatically changed in the last decade. It is now accepted that in addition to being essential intracellularly, mitochondria can promote cellular repair when transferred from healthy to damaged cells. The artificial mitochondria transfer/transplant (AMT/T) group of techniques emulate this naturally occurring process and have been used to develop therapies to treat a range of diseases including cardiac and neurodegenerative. Mitochondria accumulate damage with time, resulting in cellular senescence. Skin cells and its mitochondria are profoundly affected by ultraviolet radiation and other factors that induce premature and accelerated aging. In this article, we propose the basis to use AMT/T to treat skin aging by transferring healthy mitochondria to senescent cells, possibly revitalizing them.
Mutations related to monogenic mitochondrial disorders can cause fragmentation of the mitochondrial network in the cell. Affecting this network hampers its capacity to maintain mitochondrial DNA (mtDNA) stability. When good and damaged mitochondria are unable to fuse within networks, they can't exchange healthy mtDNA or get rid of damaged DNA copies. This ultimately leads to dysfunctions in the cell and premature senescence. For instance, patients with fibromyalgia suffer from oxidative stress and inflammation of the skin which has been linked to mitochondrial dysfunction. Healthy skin depends on the maintenance of functional mitochondria, which could be a target for the development of medical and cosmetic anti-aging treatments.
To our knowledge, there is no effective treatment available to the public to reverse skin aging by targeting mitochondria. The few existing therapeutic options focused on the mitochondria are under development and still, need further in vitro assays and clinical validation. In addition, no available products, including topical application of natural substances and antioxidants, offer a substantial recovery from many skin aging symptoms such as mtDNA instability, respiration, collagen production, neovascularization, and localized inflammation.
In this hypothesis article we present the idea and arguments of using the artificial mitochondria transfer/transplant (AMT/T) technique as a possible skin anti-aging therapeutic. It has been observed previously that the use of AMT/T in vitro, in vivo, and clinically promotes cell and tissue recovery in different diseases, with effects that could be used to repair skin damage. For example, MitoCeption, one of many AMT/T techniques, induces cell proliferation, migration, and increased respiratory ATP production, processes needed to repair the damage in aged skin. PAMM MitoCeption (Primary Allogeneic Mitochondria Mix Transfer by MitoCeption) repaired UV radiation damaged cells by recovering the loss of metabolic activity, mitochondrial mass, mtDNA sequence stability in addition to decreasing p53 expression. Beyond in vitro applications, AMT/T showed to have regenerative effects in vivo, in diseases such as heart and brain ischemia. AMT/T applied clinically to pediatric patients with myocardial dysfunction has also shown positive results on ischemic injured tissues.
Our hypothesis regarding AMT/T as an antiaging skin therapeutic could be tested in vitro, in vivo, and clinically, to promote the applications of this technique. The possibility to transfer new mitochondria to senescent or age-induced harmed cells in the skin could represent a plausible option to treat the effects of aging.