Delivery of Young Mitochondria to Old Mice Improves Cognitive and Motor Function

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.


Well, anything that you can just inject that gets a measurable result looks like progress to me. Where do you think they got the mitochondria from? Would animal mitochondria be OK for humans (I'm guessing not).

We're missing a lot of information in this story, of course. How many animals and how old? How was the mitochondria sourced, measured and delivered? What kind of testing was performed on the animals, and how statistically significant was it?

Posted by: Paul at March 6th, 2020 8:02 PM

My question is this: Is this possible to do in humans? And specifically where would the mito come from?

In this study the young mito was harvested from the liver of young mice. Is that possible to do in humans?

Posted by: Freddy at March 6th, 2020 8:04 PM

I really liked seeing this. This is a very optimistic sign for the future. If memory serves correct, Aubrey de Grey once said that aging was just a matter of damage vs repair. Elsewhere, it has been said that health is just a matter of energy vs stress. So tying both parallels together, alongside the study, if the oxidative activity goes up sufficiently enough to restore energy and metabolism, courtesy of the mitotherapy, then health should theoretically accompany to some degree, which should thus reduce stress, and thus create a positive cycle. If sufficient enough, then there will be greater energy than stress, which will give an excess of energy to offset damage in need of repair, thus getting the body out of cellular debt(so to speak). Said differently, if your furnace only generates enough energy to raise the internal temperature of the house by 10 degrees while in winter weather that is 15 below, then damage is going to occur, with pipes freezing and bursting, and then the furnace itself going out, if cold continues to progress. If energy is not sufficient, everything begins to falter and fail. It's essentially the backbone. No fuel, no motion; life becomes winter.

There was a good article I just read that alluded to the energy crisis in terms of regeneration of the nervous system. If it is okay, I will post it here. Most of the info on the energy crisis vs regeneration is towards the bottom, but it is worth the read in entirety.

Posted by: Adam at March 6th, 2020 9:19 PM

The procedure seems quite straightforward and simple. You just inject mitochondria. In humans this delivery mechanism might not be very efficient since our bodies are much larger and the tissues much thicker. In mice the mitochondria can percolate faster. On the other hand, just yesterday I saw an article about macrophages delivering mitochondria to various tissues.

I guess for humans the mitochondria will be cultured by induced pluripotent stem cells. I am not sure if we can use transplant from different people. Mitochondria seem small enough not to have individually specific antigens. If we can use off-the shelf mitochondrial injections then this treatment will become quite affordable. On the other hand, if they have to be personalized the price will be much higher and time to market will be way longer.

I didn't read the original research, but could it be that all the benefits are actually due to some signaling factors instead of the mitochondria themselves?

Posted by: Cuberat at March 6th, 2020 10:25 PM

All mitochondrial DNA comes from your mother, right? So you have the same mitochondrial DNA as you siblings and your mother. And so does your mother, and grandmother, etc. Does this mean we all have the exact same mitochondrial DNA? Would that make mito transplantation easier with no chance of rejection? If yes, you could use the blood of any young child and filter out the mitochondria.

Posted by: Ray at March 7th, 2020 3:49 AM


No, we do not all have the same mitochondrial DNA. But that might not matter if, as cuberat says, humans lack a mechanism to identify foreign mitochondria.

Posted by: Gheme at March 7th, 2020 6:03 AM

@Cuberat - perhaps stick mitochondria in Oisin's non toxic lipid nanoparticles for better distribution in larger animals like humans.

It would be interesting to see this approach for sarcopenia.

Posted by: jimofoz at March 7th, 2020 7:40 AM

Also, why has this study taken such a long time to be done? I would have thought that this could have been done back in the 2000s or even the nineties?

Posted by: jimofoz at March 7th, 2020 8:07 AM

But they mitochondria do all come from your mother, right? Do my brothers and sisters have the same mitochondrial DNA as I have?

Posted by: Ray at March 7th, 2020 8:11 AM

Can mitochondria be cultivated in a petri dish like cells?

Posted by: Abelard Lindsey at March 7th, 2020 10:15 AM

Mitochondia length generally within 0.5 - 10um . The best delivery vehicle might be exosomes - length 70-100um i- e non toxic, non allogeneic, lipid particles - see jimofoz above.

Best production of mitochondria probably via stem cells ie will be new young cells with new young mitochondria The production of stem cells for therapy is already standardised and advanced at clinical and commercial grade. I do not see why they cannot be delivered as a drink. Exosomes are known to cross the gut membrane. Possibly, there is an element of this already in operation via cow's milk. Increased cow's mild intake known to be associated with lowered risk of cognitive impairment. Not quite the same as pure anti-ageing ,I know, but connected.

Posted by: JLH at March 7th, 2020 12:05 PM

There were many mental blocks. There were probably some techolognical too. The first free mitochondria to be detected were presumed to be debries of dead cells that have burst. After all, to have stand -alone mitochondria is like having an independent engine without a car running on the highway. That was quite mental leap. For you and me it is a forgone knowledge with the benefit of hindsight. And then there were other papers on cells transferring mitochondria to each other. Now I will not that surprised if there are horizontal mito transfers across species.

Posted by: Cuberat at March 7th, 2020 1:12 PM

I did read the article and they never mention of using genetically identical mice to be donors of the mitochondria.

Posted by: Cuberat at March 7th, 2020 1:14 PM

Therefore off-the-shelf treatments will be quite plausible . I'm not sure whether non- human mitochondria can be used for implantation but having stem cell lines cultivated to produce high-quality mitichibdrua , possibly with a few lines to better match general human types

will be highly promising. Of course, all this is predicated on the fact that this study has to be confirmed andn the replicated with humans (except the part that you butcher a young individual to harvest the mitochondria from their liver)

Posted by: Cuberat at March 7th, 2020 1:20 PM

@Abelard Lindsey
Probably not stand-alone mitochondria cultivation but since be they are present in almost every cell, they for sure can be cultivated from stem cells. Then you will have to tweak the cells to produce more and higher quality mitochondria and probably induce the cells to shed then as within vesicles. Sounds almost like a proto-virus. Then find best ways to deliver them to the most impacted tissues.

For first human studies, we can use cord blood , which is discarded after birth. If it works well, then we can concentrate on cultivation and mad production. If this study is confirmed and works well in humans we will have another silver bullet with impact on the scale of senolitics. Or could also be used to cure genetic mitichobdrial diseases. Those are rate and extremely expensive to treat. Here you can take some cord blood , purify it and simply inject it. Not free but quite doable on lean budget.

Posted by: Cuberat at March 7th, 2020 1:31 PM

The new mitos will probably perish in a while for the same reason they old did. Lack of quality mitophagy/QA/overwhelming mito dmg

Posted by: Johannes at March 7th, 2020 5:07 PM

Even if they die they still can be injected periodically, as long as it works.

Posted by: Cuberat at March 7th, 2020 6:07 PM

There are not enough mito in blood to make harvesting from blood practical. The most efficient way to harvest mito from mice may have been to kill them and take their livers but there would be better ways to extract from humans. I am thinking the best harvest method would be to perform fat liposuction on young teen children or 18/19 year olds if consent was an issue. Sell your mitochondria for cash! And I do not anticipate problems with allogenic transfers, but it would probably be prudent to select donors with a similar ethnic background. It may even turnout that some donors will have genetically preferable mito DNA and will be able to charge a premium

Posted by: JohnD at March 8th, 2020 8:43 AM

You get all your mitochondria from mom, but they are not necessarily all exactly the same - - heteroplasmy. Also, there's sometimes a sort of mismatch between nuclear and mtDNA. If you want an interesting overview, watch Doug Wallace's talk at the NIH from a few years back"

OT: The grossly inadequate response to Covid-19 shows our society's utter lack of compassion for the elderly and infirm. An utterly defeatist (or some might use the term 'deathist') approach in the US and much of Europe thus far. Schools should be closed NOW.
And once again - SK kicks a--.

Posted by: CD at March 8th, 2020 12:31 PM

@CD: The response is grossly inadequate because it's grossly exagerated, to the point of spreading mass hysteria. A simple example:

Last winter (2018-2019), in the US, there were 41,300,000 cases of flu and 57,300 people died. OTOH, Covid-19 caused 260 cases thus far and 16 deaths in the US. So New York declares the state of emergency. Due to flu? No, due to coronavirus! *facepalm*

Posted by: Antonio at March 8th, 2020 2:21 PM

Seasonal flu is bad and we should do more to prevent it such as free flu shots and paid sick days for food service and retail workers (the latter would also help reduce the numbers of cases of foodborne illnesses).

Best estimates at this time are that 5% of people with covid-19 require supportive care and the virus has an R0 of around 2 (similar the 1918 flu). If it is uncontrolled then hospital systems will be overwhelmed and there will not be enough beds, ventilators, etc. and the fatality rate will be higher than if measures for control are taken NOW.

Most people are unconcerned since they are under age 60 and are in relatively good health (or perhaps some are particularly well connected and are on remdesivir).

Posted by: CD at March 9th, 2020 10:00 AM

Sorry if this is much OT but, in answer to CD:

Covid-19's mortality rate outside Wuhan is 0.7%. Flu's mortality here in Spain is 1.2%. I couldn't find the number for the US, since it's mixed with pneumonia's mortality, giving a total of 6.9% for both:

Point is, flu is much worse than coronavirus, both in absolute and relative terms, but government and media reactions aren't at all comparable. For the latter, there is a clear mass hysteria.

Posted by: Antonio at March 9th, 2020 12:06 PM

Covid-19's case fatality rate in Italy is ~ 3.6%. The CFR will increase if hospitals are overwhelmed. It is useless to compare the total deaths from Covid-19, which emerged as a human pathogen only in mid-December 2019, with total seasonal flu deaths. Also, Covid-19 is more similar to SARS and MERS, both of which can cause permanent lung damage. Patients with Covid-19 can wind up on ventilators for over a month. Some need ECMO. If you want an honest assessment of the situation from a medical professional, watch Dr John Campbell's channel (he teaches people how to properly wash their hands - how 'hysterical' /s ):

Posted by: CD at March 9th, 2020 12:39 PM

... and yes, I know people can wind up on ventilators and ECMO from seasonal flu, also - and flu strains resources enough as it is, so if nothing is done to slow down the Covid-19 outbreak we will not be able to provide supportive care to all who need it.

Posted by: CD at March 9th, 2020 12:45 PM

Some claims (autopsy of Chinese Covid survivors who died of other causes like road death weeks later) it will leave everyone with permanent pulmonary fibrosis. If that is true it would be a good door opener on treatments for pulmonary fibrosis-

Posted by: arren brandt at March 9th, 2020 11:39 PM

Here we are at April 2, 2020. It seems CD was the insightful one. CD if you read this would love to hear your comments now. Others, branch beyond fox news.

Posted by: august33 at April 2nd, 2020 10:03 PM
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