Fight Aging!

Mitochondria are the power plants of the cell, hundreds of them working to generate copies of the energy store molecule ATP, used to power cellular operations. Declining mitochondrial function is thought important in aging, disruptive of the ability of cells and tissues to function correctly, and a large body of scientific literature supports a contributing role for mitochondrial dysfunction in many age-related conditions. With advancing age, changes in gene expression in cells, reactions to the deeper damage and dysfunction of aging, lead to mitochondria that are both inefficient in producing ATP and resistant to clearance by the quality control mechanisms of mitophagy. It is also possible for damage to mitochondrial DNA to produce cells overtaken by malfunctioning mitochondria, and these problem cells make an outsized contribution to oxidative stress in tissues.

What can be done about this? There are many potential strategies, with various degrees of effectiveness. At present there is evidence from NAD+ upregulation and mitochondrially targeted antioxidants to suggest that means of restoring mitophagy can improve mitochondrial function. These particular approaches may be little more effective than exercise in achieving this goal in humans, however. The evidence for better outcomes is still mixed and limited. The SENS Research Foundation is working on copying mitochondrial genes into the cell nucleus to ensure that mitochondrial DNA damage doesn't result in dysfunctional cells, but this doesn't solve the other half of the problem. Reprogramming of cells from old tissues restores youthful epigenetic patterns and mitochondrial function, and a number of groups are working towards the development of reprogramming techniques that can be used in vivo. And so forth.

One of the more interesting findings of recent years is that mitochondria can be ingested by cells and put to work. Cells transfer mitochondria between one another under some circumstances. Further, there appears to be a sizable contingent of free-roaming mitochondria outside cells, perhaps employed as a form of intracellular signaling. Thus, why not periodically infuse an older patient with large amounts of pristine, undamaged mitochondria, to be taken up by cells and put to work? Researchers here demonstrate that this approach to therapy results in functional improvements in older mice.

Improvement of cognitive and motor performance with mitotherapy in aged mice

Mitochondrial dysfunction, including decreased oxidative phosphorylation capability and increased reactive oxygen species (ROS) production, is substantially responsible for aging and age-related features. Studies in various organisms, such as nematodes, Drosophila, rodents, and humans, have strongly supported that aging is closely associated with mitochondrial dysfunction. Thus, protection of the mitochondrial structure or stimulation of mitochondrial function is considered as practical ways in anti-aging. However, since most of the mitochondrial damage is irreversible during aging process, the agents can always provide limited protection.

Mitochondrial therapy (mitotherapy) is to transfer functional exogenous mitochondria into mitochondria-defective cells for recovery of the cell viability and consequently, prevention of the disease progress. Accumulating evidence has indicated that exogenous mitochondria can directly enter animal tissue cells for disease therapy following local and intravenous administration. In our recent reports, systemic injection of isolated mitochondria could reduce liver injury induced by acetaminophen and high-fat diet through improving hepatocyte energy supply and decreasing oxidative stress. Therefore, we assumed that the mitochondria isolated from young animals (young mitochondria) into aged ones might play a role in anti-aging.

In this study, we intravenously administrated the young mitochondria into aged mice to evaluate whether energy production increase in aged tissues or age-related behaviors improved after the mitochondrial transplantation. The results showed that heterozygous mitochondrial DNA of both aged and young mouse coexisted in tissues of aged mice after mitochondrial administration, and meanwhile, ATP content in tissues increased while reactive oxygen species (ROS) level reduced. Besides, the mitotherapy significantly improved cognitive and motor performance of aged mice. Our study, at the first report in aged animals, not only provides a useful approach to study mitochondrial function associated with aging, but also a new insight into anti-aging through mitotherapy.