17 replies to this topic

[resveratrol_guy]

The statistical firmity of this conclusion is weak, but further investigation is warranted due to the out-of-band lifespan, which is impressive for such a narrow therapy which has already been done in humans thousands of times, and moreover because the study involved human MSCs. Unlike with caloric restriction, which works much more effectively in short-lived species, mostly likely because the stress response evolved in the context of merely multiweek spans of environmental inadequacy, periodic administration of MSCs have no such implied limitations, and therefore might be expected to work similarly in humans, if chronically administered throughout adult life. In practice, this suggests (1) freezing one's stem cells (Caladrius Biosciences etc.) and (2) culturing said stem cells in order to expand the supply, thus affording longterm administration. Furthermore, considering that bone marrow therapy does not approach the broad epigenetic impact of caloric restriction, it seems likely that this strategy could be combined with other life extension therapies in order to achieve additional life extension. Again, more studies are justified. Meanwhile, it's time for me to thaw out some of my stem cells...

 

"Background: There is a growing interest in the potential of mesenchymal stem cells (MSC) for implementing regenerative medicine. Methods: We assessed the effect of intravenous administration of human bone marrow-derived MSC on the lifespan of a single Sprague-Dawley female rat. The treatment was started when the rat was 6 months old and the cells were administered every two weeks afterwards. Results: The treatment did not induce any obvious changes in body growth or behavior and the rat showed the typical age changes for this strain, except that, unlike intact counterparts, the animal did not develop mammary tumors or pituitary gland hyperplasia. The more remarkable effect of the treatment was on lifespan which was 44 months as compared with an average of 36 months for intact laboratory rats. Conclusions: We conclude that despite the low N value it is likely that the MSC treatment was responsible for the exceptionally long survival of the rat. The potential rewards of confirming the present findings warrant further studies involving higher N values."

 

http://online.lieber...9/rej.2015.1777

 

Edited by resveratrol_guy, 27 January 2016 - 05:44 PM.

[corb]

Ties in into: http://stemcellstm.a...ntent/4/10/1144 which was posted on the news section.

 

[Turnbuckle]

N=1 with no controls? No conclusion is possible.

[corb]

I remember there was a much better and conclusive study with mesenchimal stem cells from a month or two back in the news section.

 

[resveratrol_guy]

N=1 with no controls? No conclusion is possible.

 

There is a point at which the most mundane explanation is the action of the supplemented stem cells as opposed to luck. It's not as if we know nothing about such benefits or have no expectation whatsoever; we just know very little.

 

The question is, is 22% sufficiently compelling? I'm no expert on rat lifespans, but it seems to me that this is squarely in the gray area. So I would, at least, say that they should get funded for more research. Unfortunately, this would encourage similarly vague N=1 studies in the future, which I think are a waste but tend to maximize funding duration.

Edited by resveratrol_guy, 31 January 2016 - 01:30 PM.

[Turnbuckle]

 

The average litter size of the Sprague Dawley rat is 10.5. The adult body weight is 250–300g for females, and 450–520g for males. The typical life span is 2.5–3.5 years. These rats typically have increased tail to body length ratio compared with Wistar rats.

 

http://www.albany.edu/mcnaylab/sd.html

 

 

So all we can say with an n of 1 is that it lived 2 months beyond the typical life span. So 5% rather than 22%.

[resveratrol_guy]

 

 

The average litter size of the Sprague Dawley rat is 10.5. The adult body weight is 250–300g for females, and 450–520g for males. The typical life span is 2.5–3.5 years. These rats typically have increased tail to body length ratio compared with Wistar rats.

 

http://www.albany.edu/mcnaylab/sd.html

 

 

So all we can say with an n of 1 is that it lived 2 months beyond the typical life span. So 5% rather than 22%.

 

 

Based on what you cited above, the center of the distribution is close to 3 years, or 36 months. If we had an actual distribution for this rat's particular genome, we could calculate a more accurate estimate. But in the absence of that, the most unbiased assumption would be to take the middle of the above interval. It's not the most conservative assumption, however, which is simply that it was all due to luck. If your point is that N=1 is really annoyingly weak, I agree.
 

Edited by resveratrol_guy, 01 February 2016 - 07:08 AM.

[Turnbuckle]

 

 

 

 But in the absence of that, the most unbiased assumption would be to take the middle of the above interval. 

 

 

Change unbiased to self-deluding and I might agree with you. Imagine doing n=1 experiments on hundreds of substances. Half the rats would show up to six months improvement over the mean lifespan and the other half would show up to six months reduction. Using this "research" you could combine the best substances into a longevity pill and the worst ones into rat poison. All very exciting (and profitable!) but every last bit from natural variation. 

 

This is the error some make by pointing to Linus Pauling as evidence vitamin C increases lifespan. He took grams of C every day and lived to 92, and while that is a long time, people who don't take C and smoke cigars sometimes live longer than that, so just one case doesn't have statistical significance.

 

Below are the results of trials of vitamins C and E in voles. Notice that if you had an n=1 experiment and your animal happened to fall in the latter part of the C or E curves, you might conclude that these antioxidants extended vole lifespan rather than the reverse.

Attached Files

•  Voles.JPG   45.24KB   2 downloads

Edited by Turnbuckle, 01 February 2016 - 11:41 AM.

[resveratrol_guy]

I get your point, and to be sure, it cannot be underemphasized how inadequate N=1 is for biomedical applications. But it's important to pay attention to the fraction of the distribution which is at least as far from the mean as 44. It's not microscopic, but it's small. To say that N=1 has no significance whatsoever is only true in the absence of any other facts whatsoever. Otherwise, if the rat lived a billion years, we would still throw it out as an uninformative N=1 data point. The math does not support such abject dismissal because we do have some reasonably accurate expectations here, in addition to dirty evidence in favor of stem cell efficacy at supporting rejuvenation.

 

Would I recommend stem cell therapy for the purposes of life extension based on this rat? No, and not even for rats! But I would throw a few dollars to the researchers because it seems likelier than not that it's worth studying this further.

[Turnbuckle]

There's no need to hang your hat on a N=1 experiment when there's other research out there--

 

 

DURHAM, N.C., Aug. 27, 2015 /PRNewswire-iReach/ -- A new study appearing in STEM CELLS Translational Medicine indicates that stem cell injections helped rats live almost a third longer than normal. In addition, the treated animals remained both physically and mentally active longer throughout their life spans.

 

The study was conducted by researchers in Korea, led by Yun-Bae Kim, D.V.M., Ph.D., at Chungbuk National University's College of Veterinary Medicine, and Jeong Chan Ra, D.V.M., Ph.D., at the Biostar Stem Cell Research Center, Biostar Group, in Seoul.

 

Aging is characterized by the loss of regenerative capacity of cells and tissues, leading to the shrinkage of body mass and increased susceptibility to stress. "When new cells are not able to replace the ones that die, tissue integrity and functions decline. Therefore, it has been suggested that exhaustion of stem cells may be a major cause of aging in humans and that the proliferative potential of stem cells is related to life span," said Dr. Kim.

 

His group wondered whether replenishing stem cells might have an anti-aging effect. Their curiosity was sparked by studies conducted on mice suffering from progeria, an extremely rare genetic disorder that causes premature aging. The animals' lives were extended after receiving stem cell treatments. Other studies indicated improved cognitive function in mice with Alzheimer's disease that were also treated with stem cells. 

 

The Kim-Ra team decided to test whether stem cell treatments might have the same benefits for healthy animals.

 

To carry out their study, they divided 10-month-old male rats into two groups and intravenously transplanted each group with either human amniotic-membrane-derived mesenchymal stem cells (AMMSCs) or adipose-tissue-derived mesenchymal stem cells (ADMSCs). The transplantations were carried out once a month for the remainder of the animals' lives. The animals were compared to a control group of 7-month-old rats that received no cells.

 

At the end of the 20-month study, only 30 percent of the control group survived, compared to 70 percent and 100 percent of the animals in the AMMSC and ADMSC groups, respectively. "Collectively, the mean life span of the rats (604.6 days) was extended to 746.0 days (23.4 percent increase) and 793.8 days (31.3 percent increase) by treatment with AMMSCs and ADMSCs, respectively. The animals also remained both cognitively and physically active longer than normal, too," Dr. Kim said.

 

http://www.stemcells...h.PB87Md0R.dpuf

 

 

 

Edited by Turnbuckle, 02 February 2016 - 03:36 PM.

[niner]

The Kim results confirm the result with the single rat.  Kim's controls were kind of short-lived, for an F344 rat.  See for example this, reporting a 28 month median LS.

[Turnbuckle]

And here is one with a 31 month median for the male F344 rat, so the Kim lifespans do indeed seem short--

 

Inbred Strains of Rats: F344

 

Life-span and tumour incidence depend both on strain characteristics and the environment. The following has been reported: Median lifespan about 31 months in males and 29 months in females with about 87% survival to 24 months in both sexes. (Sass et al 1975). 

 

http://www.informati...docs/F344.shtml

 

 

The mean Sass control rat lived 56% longer than the Kim control rats and 19% longer than the Kim ADMSC treated rats, all supposedly of the same strain. So this doesn't give one a lot of confidence in their results. 

Edited by Turnbuckle, 03 February 2016 - 11:53 AM.

[corb]

That is quite worrisome, the results looked quite good on the surface before this information.

On the other hand if the rats had lived longer than the median this study would have been in direct contradiction to the other paper posted during the same week or so that pointed out that only genetically analogous stem cells produce median lifespan changes in rats.

[niner]

The Kim rats were being injected frequently (vehicle only for controls).  This is pretty stressful for rodents, and might explain the shorter life of the controls.  The point of controls is that they are living in identical conditions to the treatment group, and if the treatment made the rats more robust against whatever stress they were under, I think that's an important result.   Otherwise, you'd have to postulate that if the environment was supremely benign, the stem cells wouldn't have done any good at all, which seems kind of unlikely.

[resveratrol_guy]

There's no need to hang your hat on a N=1 experiment when there's other research out there--

 

DURHAM, N.C., Aug. 27, 2015 /PRNewswire-iReach/ -- A new study appearing in STEM CELLS Translational Medicine indicates that stem cell injections helped rats live almost a third longer than normal. In addition, the treated animals remained both physically and mentally active longer throughout their life spans.

 

The study was conducted by researchers in Korea, led by Yun-Bae Kim, D.V.M., Ph.D., at Chungbuk National University's College of Veterinary Medicine, and Jeong Chan Ra, D.V.M., Ph.D., at the Biostar Stem Cell Research Center, Biostar Group, in Seoul.

 

Aging is characterized by the loss of regenerative capacity of cells and tissues, leading to the shrinkage of body mass and increased susceptibility to stress. "When new cells are not able to replace the ones that die, tissue integrity and functions decline. Therefore, it has been suggested that exhaustion of stem cells may be a major cause of aging in humans and that the proliferative potential of stem cells is related to life span," said Dr. Kim.

 

His group wondered whether replenishing stem cells might have an anti-aging effect. Their curiosity was sparked by studies conducted on mice suffering from progeria, an extremely rare genetic disorder that causes premature aging. The animals' lives were extended after receiving stem cell treatments. Other studies indicated improved cognitive function in mice with Alzheimer's disease that were also treated with stem cells. 

 

The Kim-Ra team decided to test whether stem cell treatments might have the same benefits for healthy animals.

 

To carry out their study, they divided 10-month-old male rats into two groups and intravenously transplanted each group with either human amniotic-membrane-derived mesenchymal stem cells (AMMSCs) or adipose-tissue-derived mesenchymal stem cells (ADMSCs). The transplantations were carried out once a month for the remainder of the animals' lives. The animals were compared to a control group of 7-month-old rats that received no cells.

 

At the end of the 20-month study, only 30 percent of the control group survived, compared to 70 percent and 100 percent of the animals in the AMMSC and ADMSC groups, respectively. "Collectively, the mean life span of the rats (604.6 days) was extended to 746.0 days (23.4 percent increase) and 793.8 days (31.3 percent increase) by treatment with AMMSCs and ADMSCs, respectively. The animals also remained both cognitively and physically active longer than normal, too," Dr. Kim said.

 

http://www.stemcells...h.PB87Md0R.dpuf

 

 

 

Impressive, especially considering that, as in the N=1 case, these were human MSCs. It's interesting that adipose performed better than the amniotic variety, although I don't want to read too much into 793 vs 746; perhaps adipose stem cells are slightly less carcinogenic.

 

Considering the followup comments above, niner seems right that stem cells help more diseased or stressed individuals to a greater extent than healthy ones. After all, we don't see any world records being broken by atheletes who use prolotherapy or whatever; considering the hype value of such a story, we probably would have heard of that by now. But is this a problem? I think it's actually just another good reason to freeze one's stem cells at some point after 25 when the economics are justifiable.

 

By the way, do you folks know if frozen stem cells can be cultured in order to enlarge supply? I would expect this to be routine at this point, but oddly enough I haven't seen so much as a quack outfit which offers such a service.

[Turnbuckle]

The Kim rats were being injected frequently (vehicle only for controls).  This is pretty stressful for rodents, and might explain the shorter life of the controls. 

 

 

If that were true, someone would have published it by now and the anti-vaccine crowd would be using it as ammunition.

[sub7]

Unless one has vast, vast funds available, is it a good use of money to freeze stem cells, given that

 

1- Scientists have been able to make stem cells from fat cells already

http://www.scienceal...sue-in-the-body

 

2- Using stem cells from an unrelated donor does not seem to trigger immune reaction/rejection

https://med.stanford...e-patients.html

 

Just as importantly, are stem cells a dead-end? Peter Nygard had invested lots of money into stem cells and was supposedly brave enough to have them injected into himself. That was already 2.5 years ago. Had there been progress -considering that he loves media exposure- we'd have heard something by now, no?

http://www.ibtimes.c...-nygard-1438362.

[corb]

Unless one has vast, vast funds available, is it a good use of money to freeze stem cells, given that

 

1- Scientists have been able to make stem cells from fat cells already

http://www.scienceal...sue-in-the-body

 

2- Using stem cells from an unrelated donor does not seem to trigger immune reaction/rejection

https://med.stanford...e-patients.html

 

Just as importantly, are stem cells a dead-end? Peter Nygard had invested lots of money into stem cells and was supposedly brave enough to have them injected into himself. That was already 2.5 years ago. Had there been progress -considering that he loves media exposure- we'd have heard something by now, no?

http://www.ibtimes.c...-nygard-1438362.

 

Stem cells are NOT a dead end, but they are a science which was for a long time in it's infancy - and yet was hyped long before it was ready for prime time - it's not ready even as speak of it right now.
It's getting there though, but the marketing damage has already been done and people think stem cells are some sort of charlatanry now. The shady clinics made boatloads of money by praying on the desperate and gullible.

Anyway, I'm not sure if it's a good idea to freeze your stem cells. If you're strapped for funds probably not.