Life Extension in Old Mice via Transplant of Bone Marrow Cells From Young Mice

The research noted here, in which scientists transplant young stem cells into old mice, is a logical exploration of the bounds of the possible along the lines of parabiosis studies, in which the circulatory systems of old and young individuals are linked. The results demonstrate that regular cell transplants incorporating young bone marrow stem cells can extend life when provided to older individuals, provided there is a close genetic match between donor and recipient. Without that match there was no effect on life span:

The method of lifespan extension that is a practical application of the informational theory of aging is proposed. In this theory, the degradation (error accumulation) of the genetic information in cells is considered a main cause of aging. According to it, our method is based on the transplantation of genetically identical (or similar) stem cells with the lower number of genomic errors to the old recipients. For humans and large mammals, this method can be realized by cryopreservation of their own stem cells, taken in a young age, for the later autologous transplantation in old age.

To test this method experimentally, we chose laboratory animals of relatively short lifespan (mouse). Because it is difficult to isolate the required amount of the stem cells (e.g., bone marrow) without significant damage for animals, we used the bone marrow transplantation from sacrificed inbred young donors, males and females of 1.5-3 months. Bone marrow transplantation (2 × 10^6 cells) was performed with the intervals of 3 months to the death of the animal. Experiments were started at age of 7-8 months for the recipients of the first and the second experimental groups and at age of 6-10 months for those of the third group.

It is shown that the lifespan extension of recipients depends on level of their genetic similarity (syngeneity) with donors. We have achieved the lifespan increase of the experimental mice by 34% when the transplantation of the bone marrow with high level of genetic similarity was used. The value of lifespan increase in our experiments varies from 34% for high-level syngeneic transplantation to 0% for allogeneic transplantation.

Link: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4605449/

Comments

This is the fourth, and poorest, in a series of unconvincing reports of this general sort (PMIDs 20179893, 26315571, & 22355586). The cohort sizes were too small; the "old" recipient mice were still quite young adult; the reportedly superior LS extension in the first group is an artifact of having a control group whose mean LS was aberrantly low compared to all other groups' controls (the second, less-closely-related group of recipients actually lived longer (22.6±1.6 mo) than the first, most-related group (20.6 ±2.2 mo), although within the SEM); and ALL of the mice in this study lived ridiculously short lives, intervention or not: the Original Sin of biogerontology. It's no wonder this is in a biophysics journal, and not Rejuvenation Research or some other journal actually specializing in biogerontology — although goodness knows that much nonsense still manages to appear in the pages of journals that should know better ...

Posted by: Michael at October 27th, 2015 12:38 PM

@Michael I still see this and various other studies showing similar as confirmation of the importance of stem cells in aging and their role in restoring homeostasis. More importantly they are proof of concept of RepleniSENS surely?

The solution? Repeat experiment with better choice of mice and or rats and test with larger cohorts. This is a distinct possibility for a project like the Major Mouse Testing Project being organized by the international Longevity Alliance. Would SENS support such an initiative?

Posted by: Steve H at October 27th, 2015 1:19 PM

Steve H at October 27, 2015 1:19 PM: I still see this and various other studies showing similar as confirmation of the importance of stem cells in aging and their role in restoring homeostasis.

It looks like it might in some sense restore homeostasis in rodents that have been made miserably sick by poor husbandry or bad genetics. It has no more implications about doing so in otherwise-healthy but aging mammals than the scores (hundreds?) of studies showing that antioxidant supplements can partially normalize the shortenend lifespans of genetically- or pharmacologically-screwed-up, overfed diabetic, or incompetently-husbanded mice do: when you try the same supplements in normal, basically-healthy aging mice, you get dead mice on a normal schedule.

Steve H at October 27, 2015 1:19 PM: More importantly they are proof of concept of RepleniSENS surely?

First, a badly-done experiment isn't POC of anything in particular. But second, they really don't relate to repleniSENS: repleniSENS is the replenishment of organs and tissues that have lost cells and tissues with fresh, youthful replacements via cell therapy and tissue engineering: new neurons in the aging brain, new cardiomyocytes in the aging heart, and so on, plus the replenishment of the stem and progenitor cell pools.

Bone marrow infusion doesn't do any of this (except in the case of a true bone marrow transplant, where you're replacing bone marrow SC with bone marrow SC after depleting its native complement): it exposes various non-bone-marrow tissues to bone marrow stem cells. This sometimes has some benefits when conducted after an acute insult (for instance, a modest benefit when performed shortly after a heart attack, and in mouse models after an induced stroke), but not by way of replacing the lost cells: that idea was disproven a decade ago. Rather, it provides paracrine support to the local cells, reducing the loss to ischaemic and other acute insults.

It's certainly not a crazy hypothesis that transfusion of youthful bone marrow stem cells might provide some kind of similar benefits in advanced aging tissues, but piling on poorly-done studies like this does nothing to support the idea.

Steve H at October 27, 2015 1:19 PM: Repeat experiment with better choice of mice and or rats and test with larger cohorts.

... and start in late life, and do it in a lab that can competently husband lab animals.

Steve H at October 27, 2015 1:19 PM: Would SENS support such an initiative?

We'd certainly applaud it ;) . If you have or know of a lab with a track record of conducting well-done lifespan studies (control mice with mean and tenth-decile survivorships of ≈900 and ≈1100 days, respectively) that's interested in doing the study right, I'd encourage you/them to submit a Letter of Intent.

Posted by: Michael at October 27th, 2015 3:39 PM

@Michael the Major Mouse testing program is proposing to test such interventions and have three labs as part of the study with the following researchers:

Alexandra Stolzing http://www.researchgate.net/profile/Alexandra_Stolzing/info
Arlan Richardson http://www.ouhsc.edu/roca/OurPeople/ArlanRichardson,PhD.aspx
Jean-Marc Lemaitre http://www.researchgate.net/profile/Jean-Marc_Lemaitre

We are looking at 3 or so interventions as the initial phase in already aged mice. Michael Conboy has made some suggestions regarding interventions to test but its hard given how many possible things we have in our suggestion list.

Hopefully we can look at Stem cells and repeat this experiment properly. I will keep you informed.

Posted by: Steve H at October 27th, 2015 3:51 PM

@Michael also are you following the progress of the artifical niche techniques at John Hopkins and Harvard? These hydrogels allow stem cells to hang around longer sending the paracrine signals out to help healing but interestingly seem to increase the engraftment rate as well as resisting the aged system inhibiting them.

It would be interesting to test such gels as a later follow on phase to the initial testing.

Posted by: Steve H at October 27th, 2015 4:31 PM

As a Physician, I like their line of reasoning (but not necessarily the study design.) I think ALL Humans should have the opportunity to have a bone marrow tap (!Painful) and have it frozen like sperm or eggs. This would accomplish Several things:

1. If you had a radiation overdose from a nuclear bomb, you could be saved.

2. If you had leukemia, or even a solid tumor (like breast) that can spread to the bone marrow,
you could also be saved. Knock out the Old marrow put in the new. It is an amorphous substance so no Surgery is required.

3. NOT so sure about the "Fountain of Youth" stuff, BUT almost ALL chronic diseases have at their root a dysfunctional immune system. Alzheimer's is because the immune cellls can't clear the plaques and tangles. That's why it's more Common to the 85 and Older Crowd. WHO gets it in their Thirties, Forties and Fifties?? Aside from some with a rare mutation, AIDS patients get HIV Dementia. The exact cause is uncertain but their brains All look like Dementia Brains. This is actually More of a problem with the HAART therapies of the last twenty years, as the Patients are in remission with no Opportunistic infections to kill them, but the Brain Damage is still there. There are lots of thirty year olds in the Nursing Home because of this.

PS: Years ago they joined together the circulatory systems of old and young mice, and This made the old mice vigorous and increased their lifespan. They found out why two years ago. There is a protein that can regenerate the Brain, and perhaps the heart and kidney of older Mice. This SAME protein is known to exist in the Human Body. The protein should be synthesized from modified e coli and trials should begin on a compassionate basis.

Posted by: Thaddeus Buttmunch at January 14th, 2016 5:29 PM

No single protein from young blood can be solely responsible for rejuvenation in old. There will be multiple factors.

Posted by: Akshay Atomic Bliss at December 15th, 2016 10:53 PM

Quite possibly True-but the Experiment is still noteworthy.

Posted by: Thaddeus Buttmunch MD at February 12th, 2017 9:16 PM

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