Any reader of a vampire novel knows that acquiring the blood of a young person is the secret of a vampire’s eternal youth. In fact, the essence of being a vampire is a constant quest for such acquisition. According to a news stories that broke today, it seems like scientific knowledge is finally catching up.
It is also common knowledge among us longevity-science types that somatic stem cells are subject to senescence and that, with aging, these stem cells progressively lose their capability to reproduce and differentiate. (See the discussion in my treatise related to the Stem Cell Supply Chain Breakdown theory of aging.) “Buildup of levels of Ink4a/P16 associated with aging slows down the rate of differentiation of adult stem cells.” Further, age-related loss of capability to reproduce and differentiate has to do with what is going on in the niches in which stem cells live. “Our results reveal that aged differentiated niches dominantly inhibit the expression of Oct4 in hESCs and Myf-5 in activated satellite cells, and reduce proliferation and myogenic differentiation of both embryonic and tissue-specific adult stem cells (ASCs). Therefore, despite their general neoorganogenesis potential, the ability of hESCs, and the more differentiated myogenic ASCs to contribute to tissue repair in the old will be greatly restricted due to the conserved inhibitory influence of aged differentiated niches(ref).” Along with this decline in stem cell renewal capability comes a breakdown in the efficacy of the stem cell supply chain, aging and death. According to a January 30 2010 news item appearing in Science Daily “A team of Howard Hughes Medical Institute (HHMI) researchers has found that in old mice, a several-week exposure to the blood of young mice causes their bone marrow stem cells to act “young” again.” Dracula, why are you acting bored?
The publication related to the new research is Systemic signals regulate ageing and rejuvenation of blood stem cell niches and appeared in the January 28 issue of Nature. “Ageing in multicellular organisms typically involves a progressive decline in cell replacement and repair processes, resulting in several physiological deficiencies, including inefficient muscle repair, reduced bone mass, and dysregulation of blood formation (haematopoiesis). Although defects in tissue-resident stem cells clearly contribute to these phenotypes, it is unclear to what extent they reflect stem cell intrinsic alterations or age-related changes in the stem cell supportive microenvironment, or niche. Here, using complementary in vivo and in vitro heterochronic models, we show that age-associated changes in stem cell supportive niche cells deregulate normal haematopoiesis by causing haematopoietic stem cell dysfunction. Furthermore, we find that age-dependent defects in niche cells are systemically regulated and can be reversed by exposure to a young circulation or by neutralization of the conserved longevity regulator, insulin-like growth factor-1, in the marrow microenvironment. Together, these results show a new and critical role for local and systemic factors in signaling age-related haematopoietic decline, and highlight a new model in which blood-borne factors in aged animals act through local niche cells to induce age-dependent disruption of stem cell function.”
This does not sound much like vampire talk. Some of the press reports about the work are more lucid if not lurid. According to the Science Daily writeup “Hematopoietic stem cells give rise to all the cells of the blood system, including immune cells and red blood cells. As animals age, these stem cells become more numerous, but less effective at regenerating the blood system, Wagers says. That translates into a less effective immune system and a greater susceptibility to disease. — To see if younger blood could reverse the sluggishness of aging blood cells, the researchers began by surgically joining the bloodstreams of pairs of mice that were of different ages, but nearly clones of one another.” (Hmmn, joining bloodstreams? That does sound rather vampire-like.) “Each mouse carried distinctive genetic markers so that researchers could differentiate between its cells and those of its partner. The technique, called parabiosis, enables researchers to test the long-term effects of one animal’s blood on the tissues and organs of the other. “It’s the only model that really allows us to come close to mimicking an in vivo systemic environment,” Wagers (Amy Wagners, the lead investigator) said. “There is a constant exposure to any cell or soluble factor that circulates, at close to physiologic levels.” — After several weeks of sharing their blood systems with young mice, the hematopoietic stem cells of the older mice changed markedly. Exposure to a younger animal’s blood somehow pushed the older animal’s hematopoietic stem cells back to a more youthful state, in which they were fewer in number but recovered nearly all of their blood-cell-generating capacity. When transplanted into mice whose own blood-producing cells had been eliminated by radiation, the “rejuvenated” stem cells repopulated the blood with a mixture of cell types similar to that generated by transplanted young stem cells. No such changes occurred in the young mice in these pairings, or among age-matched pairs of animals.”
There is significantly more to the recent research findings, and that is that IGF-1 expression in osteoblasts present in the haematopoietic stem cell bone marrow niches is responsible for the decline in vitality and differentiation capabilities of haematopoietic stem cells in older mice, and neutralizing the IGF-1 in the bone marrow also restores the vitality and differentiation capabilities of these stem cells.
In more detail, ” Wagers and her team haven’t yet discovered the blood-borne factor that triggers this apparent restoration of youthfulness in aged hematopoietic stem cells. But they did find two important clues to how it transmits its effects. — First, they found evidence that this factor works via bone-forming cells known as osteoblasts, which also are present in bone marrow and help regulate hematopoietic stem cells. When old animals were exposed to young blood, their osteoblasts reverted to more youthful numbers. They also behaved more like younger osteoblasts in their interactions with hematopoietic stem cells. Hematopoietic stem cells grown in cultures with these “rejuvenated” osteoblasts regained the blood-cell-generating capacity characteristic of youthful stem cells. For osteoblasts, the opposite was also true: the bone-forming cells of young animals- from humans as well as mice — showed signs of aging when they were exposed to blood from an older animal. — The team also found that the insulin-like growth factor 1 (IGF-1) hormone appears to be necessary to maintain these stem-cell-regulating osteoblasts in an aged state. When they blocked IGF-1 activity in osteoblast cells in culture or in bone marrow, aged osteoblasts reverted to a “younger” state, and could pass that rejuvenation effect on to hematopoietic stem cells. Blocking IGF-1 activity in the bloodstream of mice didn’t have the same effect, which suggests that IGF-1 acts specifically through osteoblasts. — Oddly enough, IGF-1 is best known for its growth-promoting and potentially anti-aging effects in other tissues, including muscles and bones. “Our findings highlight the fact that IGF-1 signaling is complex and depends in part on the tissue involved,” said Wagers(ref).”
Getting back to vampires, the results of the new study suggests a cure for their centuries-old thirst for blood, since it suggests that blocking the effects of IGF-1 in bone marrow osteoblasts could have the same rejuvenating affect as the blood of a young person. Of course this would have to be validated by a clinical trial. Can you imagine a drug company setting up such a trial for vampires where half the participants take a drug that blocks bone marrow IGF-1 and the control group participants go out and hunt human victims and drink their blood in normal vampire fashion?
Seriously, there just could be some longevity benefit to selective blocking of IGF-1 in osteoblasts. More must be learned about this possibility. And the mouse results must be validated in humans.
//Can you imagine a drug company setting up such a trial for vampires where half the participants take a drug that blocks bone marrow IGF-1 and the control group participants go out and hunt human victims and drink their blood in normal vampire fashion?
For one thing I think such a clinical trial would get a lot of press. I have been thinking about writing a short sci-fi story based on the content of the post. For example, if I can confirm that garlic blocks the expression of IGF-1 in osteoblasts, that could help explain why vampires hate garlic so much, I love having fun with whatever I do.
I laughed out loud when i read your article..particularly that portion.
Yes you could write a scifi on this.
May be there is a little truth in garlic and igf-1
But it is quite complex is it not? igf block is good for some parts of your body. but bad for some other parts of your body..
I think what you say about IGF-1 is correct. The stuff seems to have many faces. At some point I might do a thorough survey of research on the substance.
I hope i’m wrong but it seems to me to be a dilution of inhitory factors in the old blood, not something in the young blood.
I hope i’m wrong
Thatis one way of looking at it. It is definitely something. I bet that within a year or so we will know.
unfortunately this particular study has been retracted by 3/4 authors:
Thank you very much for pointing this out. I guess my specuation about vampires goes out the window too.