Spermidine
EmbraceUnity 07 Oct 2009
Spermidine had a range of effects on the cells and living creatures. It suppressed processes associated with ageing, reduced free radical levels and increased lifespan. The levels of spermidine in the cells increased too (reducing levels are usually associated with increasing age although causality has not been established). In the tests on blood cells, spermidine treatment resulted in 50% of cells surviving to 12 days, compared to only 15% of the control blood cells.
Treated yeasts survived four times as long as untreated cells, while treated fruit flies lived 30% longer than the untreated ones. The lifespan of the worms was extended by 15%. The effect on the lifespan of live mice was not investigated.
Further investigation revealed that the programmed death of cells (apoptosis) was not reduced, but spermidine appeared to protect against the type of cell death that results from more traumatic cell injury (necrosis).
When cells were deprived of spermidine, yeast lifespan was reduced and free radicals accumulated. One theory of ageing (the free radical theory) suggests that it is these entities that accumulate in the body and cause oxidative stress, which leads to ageing.
I'd be especially interested in if this is synergistic with resveratrol, rapamycin, and all our other friends. Since it doesn't interfere with apoptosis, it seems that it shouldn't increase the risk of cancer. Perhaps still too early to say if it would make a good supplement for humans, but we should start studying this big time.
In fact, anyone involved with Mprize@home should get on this immediately.
Edited by progressive, 07 October 2009 - 10:53 PM.
Hedrock 08 Oct 2009
Induction of autophagy by spermidine promotes longevity
Some scients already talk about spermidine as the "holy grail of Anti-Aging"
Nevertheless autophagy is still a double-edged sword. It can lead to cell death or to cell survival, depends on what???
Edited by Hedrock, 08 October 2009 - 06:09 PM.
kismet 08 Oct 2009
Where is the eyerolling smiley when you need one? Whoever said that is acting unprofessional, unethical and talking out of their nether region (and the Mirror makes it even worse with their sub-par reporting of buzzwords).Some scients already talk about spermidine as the "holy grail of Anti-Aging"
Reduces necrosis, messes with oxidative stress and DNA methylation - great combination of not so well understood biological processes (yeah, why not supplement it). Shows a stark decrease in efficacy as complexity of the model organism rises, but untested in long lived mice (let me guess why...) Oh, and it messes with mechanisms possibly involved in carcinogensis but was only tested in organisms consisting entirely of postmitotic cells.
Perhaps? Dozens of substances with much better safety and efficacy data (e.g. metformin) are still way too dangerous for healthy people...Perhaps still too early to say if it would make a good supplement for humans, but we should start studying this big time.
Don't jump the gun. Let's first investigate the substances in some more detail. As a rule of thumb >>99% of all promising substances that "work" in lower organisms fail miserably in higher oransims, including humans.
Edited by kismet, 08 October 2009 - 07:20 PM.
lynx 10 Oct 2009
Very well said.Where is the eyerolling smiley when you need one? Whoever said that is acting unprofessional, unethical and talking out of their nether region [...]Some scients already talk about spermidine as the "holy grail of Anti-Aging"
Don't jump the gun. Let's first investigate the substances in some more detail. As a rule of thumb >>99% of all promising substances that "work" in lower organisms fail miserably in higher oransims, including humans.
Edited by Michael, 09 May 2011 - 03:34 PM.
trim quotes
1kgcoffee 11 Oct 2009
Copied from sci.life-extension
Key to a long life found
The Daily Express claims that a “wonder pill can lengthen your life by
25 years” and that researchers have found the key to the “elixir of
life”.
Although the article contains bold claims and a picture of a woman
taking a pill, no such pill exists. The research behind this story
investigated how a naturally occurring compound called spermidine
affected the age-related processes and longevity of yeast, flies,
worms, human blood cells and mice.
The laboratory-based study found that spermidine protected cells from
certain processes related to ageing and cell damage, increasing the
lifespan of the flies, blood cells, yeast and worms. Additional
studies in live mice found that cells were protected from particular
types of cell damage, but their lifespans were not reported. While the
research itself is important, any spermidine pill, as described by the
Daily Express, is many years away.
This is at least the second time that the newspaper has reported on a
supposed discovery of an elixir of life in recent months.
Where did the story come from?
The study was carried out by Dr Tobias Eisenberg and colleagues from
the University of Graz in Austria, alongside medical and academic
institutions across Europe. It was funded by the Austrian Science Fund
and the European Commission, and published in the peer-reviewed
medical journal Nature Cell Biology.
What kind of scientific study was this?
This research investigated the action of a naturally occurring
chemical called spermidine in the process of autophagy (the body’s
controlled digestion of cells or of damaged parts of cells).
Autophagy is instrumental in recycling old cells to maintain a balance
with growth and regeneration. Failures in autophagy are thought to
lead to ageing. Cellular concentration of spermidine has been shown to
decline with ageing.
The researchers investigated how spermidine affected longevity and
various age-related processes in yeast, flies, worms, human cells and
mice. To do this, they did the following:
•Applied spermidine to ageing yeast cells.
•Supplemented the diet of the fruit fly (Drosophila melanogaster) and
the nematode worm (Caenorhabditis elegans) with spermidine.
•Supplemented the drinking water of mice with spermidine for 200
days.
•Compared the lifespan of human blood cells that were cultured with
spermidine and those that were not (the control group).
The researchers also investigated the reverse: the effect that
polyamine depletion would have on cells. Biochemical analyses were
used to assess the specific effects of spermidine on age-related
processes.
What were the results of the study?
Spermidine had a range of effects on the cells and living creatures.
It suppressed processes associated with ageing, reduced free radical
levels and increased lifespan. The levels of spermidine in the cells
increased too (reducing levels are usually associated with increasing
age although causality has not been established). In the tests on
blood cells, spermidine treatment resulted in 50% of cells surviving
to 12 days, compared to only 15% of the control blood cells.
Treated yeasts survived four times as long as untreated cells, while
treated fruit flies lived 30% longer than the untreated ones. The
lifespan of the worms was extended by 15%. The effect on the lifespan
of live mice was not investigated.
Further investigation revealed that the programmed death of cells
(apoptosis) was not reduced, but spermidine appeared to protect
against the type of cell death that results from more traumatic cell
injury (necrosis).
When cells were deprived of spermidine, yeast lifespan was reduced and
free radicals accumulated. One theory of ageing (the free radical
theory) suggests that it is these entities that accumulate in the body
and cause oxidative stress, which leads to ageing.
What interpretations did the researchers draw from these results?
The researchers conclude that they have discovered that levels of
spermidine both inside and outside the cell induce autophagy, the
failure of which has been implicated in ageing.
What does the NHS Knowledge Service make of this study?
This laboratory-based study has highlighted the important role of the
naturally occurring compound spermidine in age-related processes and
lifespan. The results of this research, both in cell cultures and
mice, may be of great interest to those studying the chemical and
biological processes of ageing, and may suggest a possible area for
future research.
The Daily Express has suggested that we are a step closer to a “wonder
pill that could extend lifespan by up to 25 years”. Even if that were
true, this would be only one step forward on a very long journey: this
is early research into how a chemical affects mice and cells in a lab,
and it may never result in such a simple ‘treatment’ for ageing.
According to the Daily Express this is at least the second elixir of
life that has been discovered in just a few months (see this previous
article on long-life pills).
Even if spermidine has the potential to possible affect ageing, it
will take many more years of research including laboratory testing,
further cell studies, further animal studies, short-term clinical
trials and long-term clinical trials, to establish the safety,
benefits, drawbacks and costs of such a treatment.
The Daily Express article mentions other recently reported research
that predicts that the majority of the UK’s newborn babies will live
to beyond 100. However, this is based on the increase in life
expectancy in past years and not specifically on the advent of new
treatments.
.Links to the headlines
Wonder pill can lengthen your life by 25 years. Daily Express, October
5 2009
Links to the science
Eisenberg T, Knauer H, Schauer A, et al. Induction of autophagy by
spermidine promotes longevity. Nature Cell Biology (Published online)
October 4 2009
SOURCE: http://www.nhs.uk/ne...pill-claim.aspx
So, where can we can buy this stuff, other than the sperm bank?
I remember reading somewhere that aloe vera (which looks very much semen) contains some
Edit to add: Apparently grapefruit is an excellent source-- http://www.newser.co...slow-aging.html
Edited by 1kgcoffee, 11 October 2009 - 05:46 AM.
niner 11 Oct 2009
Gotta find a friend. Could start by buying him a drink.So, where can we can buy this stuff, other than the sperm bank?
Seriously, probably ought to wait for the mouse data, and then some.
1kgcoffee 11 Oct 2009
Gotta find a friend. Could start by buying him a drink.So, where can we can buy this stuff, other than the sperm bank?
Seriously, probably ought to wait for the mouse data, and then some.
Cool, just need to find a supplement that will flip my sexuality. LOL
VespeneGas 11 Oct 2009
Waiting for a study of women's spermidine intake and longevity.
Looks like such a study has already been conducted!
No, but seriously, more research is clearly needed.
Mind 12 Oct 2009
Perhaps still too early to say if it would make a good supplement for humans, but we should start studying this big time.
Perhaps? Dozens of substances with much better safety and efficacy data (e.g. metformin) are still way too dangerous for healthy people...
Don't jump the gun. Let's first investigate the substances in some more detail. As a rule of thumb >>99% of all promising substances that "work" in lower organisms fail miserably in higher oransims, including humans.
Just hypothesizing here: perhaps many of these promising substances are failing because they are tested in isolation. Given the extremely complex nature of human metabolism and aging, I am thinking that it will take a similarly complex intervention (several substances that modify processes within and outside cells) to get "promising results". The "holy grail' and "silver bullet" seem to be more difficult to achieve as we increase our knowledge-base about the operation of the human body. AND, it makes the SENS approach seem more attractive.
kismet 13 Oct 2009
nowayout 14 Oct 2009
Seems like an easy experiment to try for us males, being always close to a convenient supply and all that.
Edited by viveutvivas, 14 October 2009 - 12:26 PM.
Elusive 14 Oct 2009
Thanks for such a nice article!
Spermidine(C7H19N3):
Copied from sci.life-extensionKey to a long life found
The Daily Express claims that a “wonder pill can lengthen your life by
25 years” and that researchers have found the key to the “elixir of
life”.
Although the article contains bold claims and a picture of a woman
taking a pill, no such pill exists. The research behind this story
investigated how a naturally occurring compound called spermidine
affected the age-related processes and longevity of yeast, flies,
worms, human blood cells and mice.
The laboratory-based study found that spermidine protected cells from
certain processes related to ageing and cell damage, increasing the
lifespan of the flies, blood cells, yeast and worms. Additional
studies in live mice found that cells were protected from particular
types of cell damage, but their lifespans were not reported. While the
research itself is important, any spermidine pill, as described by the
Daily Express, is many years away.
This is at least the second time that the newspaper has reported on a
supposed discovery of an elixir of life in recent months.
Where did the story come from?
The study was carried out by Dr Tobias Eisenberg and colleagues from
the University of Graz in Austria, alongside medical and academic
institutions across Europe. It was funded by the Austrian Science Fund
and the European Commission, and published in the peer-reviewed
medical journal Nature Cell Biology.
What kind of scientific study was this?
This research investigated the action of a naturally occurring
chemical called spermidine in the process of autophagy (the body’s
controlled digestion of cells or of damaged parts of cells).
Autophagy is instrumental in recycling old cells to maintain a balance
with growth and regeneration. Failures in autophagy are thought to
lead to ageing. Cellular concentration of spermidine has been shown to
decline with ageing.
The researchers investigated how spermidine affected longevity and
various age-related processes in yeast, flies, worms, human cells and
mice. To do this, they did the following:
•Applied spermidine to ageing yeast cells.
•Supplemented the diet of the fruit fly (Drosophila melanogaster) and
the nematode worm (Caenorhabditis elegans) with spermidine.
•Supplemented the drinking water of mice with spermidine for 200
days.
•Compared the lifespan of human blood cells that were cultured with
spermidine and those that were not (the control group).
The researchers also investigated the reverse: the effect that
polyamine depletion would have on cells. Biochemical analyses were
used to assess the specific effects of spermidine on age-related
processes.
What were the results of the study?
Spermidine had a range of effects on the cells and living creatures.
It suppressed processes associated with ageing, reduced free radical
levels and increased lifespan. The levels of spermidine in the cells
increased too (reducing levels are usually associated with increasing
age although causality has not been established). In the tests on
blood cells, spermidine treatment resulted in 50% of cells surviving
to 12 days, compared to only 15% of the control blood cells.
Treated yeasts survived four times as long as untreated cells, while
treated fruit flies lived 30% longer than the untreated ones. The
lifespan of the worms was extended by 15%. The effect on the lifespan
of live mice was not investigated.
Further investigation revealed that the programmed death of cells
(apoptosis) was not reduced, but spermidine appeared to protect
against the type of cell death that results from more traumatic cell
injury (necrosis).
When cells were deprived of spermidine, yeast lifespan was reduced and
free radicals accumulated. One theory of ageing (the free radical
theory) suggests that it is these entities that accumulate in the body
and cause oxidative stress, which leads to ageing.
What interpretations did the researchers draw from these results?
The researchers conclude that they have discovered that levels of
spermidine both inside and outside the cell induce autophagy, the
failure of which has been implicated in ageing.
What does the NHS Knowledge Service make of this study?
This laboratory-based study has highlighted the important role of the
naturally occurring compound spermidine in age-related processes and
lifespan. The results of this research, both in cell cultures and
mice, may be of great interest to those studying the chemical and
biological processes of ageing, and may suggest a possible area for
future research.
The Daily Express has suggested that we are a step closer to a “wonder
pill that could extend lifespan by up to 25 years”. Even if that were
true, this would be only one step forward on a very long journey: this
is early research into how a chemical affects mice and cells in a lab,
and it may never result in such a simple ‘treatment’ for ageing.
According to the Daily Express this is at least the second elixir of
life that has been discovered in just a few months (see this previous
article on long-life pills).
Even if spermidine has the potential to possible affect ageing, it
will take many more years of research including laboratory testing,
further cell studies, further animal studies, short-term clinical
trials and long-term clinical trials, to establish the safety,
benefits, drawbacks and costs of such a treatment.
The Daily Express article mentions other recently reported research
that predicts that the majority of the UK’s newborn babies will live
to beyond 100. However, this is based on the increase in life
expectancy in past years and not specifically on the advent of new
treatments.
.Links to the headlines
Wonder pill can lengthen your life by 25 years. Daily Express, October
5 2009
Links to the science
Eisenberg T, Knauer H, Schauer A, et al. Induction of autophagy by
spermidine promotes longevity. Nature Cell Biology (Published online)
October 4 2009
SOURCE: http://www.nhs.uk/ne...pill-claim.aspx
So, where can we can buy this stuff, other than the sperm bank?
I remember reading somewhere that aloe vera (which looks very much semen) contains some
Edit to add: Apparently grapefruit is an excellent source-- http://www.newser.co...slow-aging.html
Hedrock 07 Dec 2009
I found a lot of studies, which confirm the suspekt, that spermidine maybe could be cancerogenic.
Here the mechanism:
Polyamines and cancer
Many polyamine studies now focus upon reduction of total body polyamines for cancer prevention, or reduction of total body organ polyamines (e.g., colon) for organ cancer prevention. Decreased intracellular levels of polyamines caused a decrease in oncogenesis by most organic toxic chemicals when carcinogenesis studies were performed in tissue culture, intact animal, or human studies. Therefore, prevention of human skin, stomach, colorectal, lung, prostate, and breast cancers studies are in progress using DFMO and other polyamine related drugs (39-42,111-121).
I'm not sure, but as I understand the text, spermidine (like other polyamines) does promote an existing cancer, which would not grow without the spermidine. So for an existing cancer it would be a deadly game.
Please be careful!
Hedrock 07 Dec 2009
I found studies which say, low spermidine levels are better for cancer prevention.
Polyamines and cancer
Sorry!
shazam 09 Dec 2009
Some bad news!
I found a lot of studies, which confirm the suspekt, that spermidine maybe could be cancerogenic.
Here the mechanism:
Polyamines and cancerMany polyamine studies now focus upon reduction of total body polyamines for cancer prevention, or reduction of total body organ polyamines (e.g., colon) for organ cancer prevention. Decreased intracellular levels of polyamines caused a decrease in oncogenesis by most organic toxic chemicals when carcinogenesis studies were performed in tissue culture, intact animal, or human studies. Therefore, prevention of human skin, stomach, colorectal, lung, prostate, and breast cancers studies are in progress using DFMO and other polyamine related drugs (39-42,111-121).
I'm not sure, but as I understand the text, spermidine (like other polyamines) does promote an existing cancer, which would not grow without the spermidine. So for an existing cancer it would be a deadly game.
Please be careful!
I was going to make a joke about cancer patients and blowjobs, but that would be in bad taste.
/lol, bad taste.
magnelectro 10 Dec 2009
Anecdotally, this reminds me of the Taoist literature on semen retention, and the fact that the French call ejaculation la petite mort. Maybe nitric oxide isn't the only reason AAKG/OKG puts an angle in your dangle.
P.S. Semen is antidepressant as well. http://www.newscient.../article/dn2457
Cynober, 1994. Can arginine and ornithine support gut functions? Gut 1994;35;S42-S45
http://gut.bmj.com/c...1_Suppl/S42.pdf
magnelectro 10 Dec 2009
Anecdotally, this reminds me of the Taoist literature on semen retention, and the fact that the French call ejaculation la petite mort. Maybe nitric oxide isn't the only reason AAKG/OKG puts an angle in your dangle.
P.S. Semen is antidepressant as well. http://www.newscient.../article/dn2457
Cynober, 1994. Can arginine and ornithine support gut functions? Gut 1994;35;S42-S45
http://gut.bmj.com/c...1_Suppl/S42.pdf
hamishm00 10 Dec 2009
tunt01 23 Dec 2009
EmbraceUnity 09 Jul 2010
Michael 09 May 2011
Polyamines (putrescine, spermidine, and spermine) are organic compounds that are found in every living cell, where they are involved in numerous biochemical and physiological activities, including cell proliferation and differentiation (1–5). The metabolic requirement for polyamines is particularly high in rapidly growing tissues, such as during normal growth and development, and in tumors (6–8). Recent studies have suggested that reducing the amount of polyamines in cells may help to slow the cancer process (9). Clinical trials are currently underway to investigate the effect of the polyamine synthesis inhibitor, difluoromethylornithine, on cancer progression, risk for recurrent polyps, and relevant biomarkers (8). Whether foods that contribute to polyamine consumption affect cancer risk is also a topic ripe for exploration.
Until recently, it was believed that polyamines were derived exclusively from endogenous (internal) synthesis. It is now widely recognized that the polyamine body pool is maintained by three primary sources: synthesis within the body, production by microorganisms residing in the intestinal tract, and contribution from the diet (1,9–13). Studies in rats indicate that 10% of dietary putrescine, 40% of dietary spermidine, and 8% of dietary spermine are retained in body tissues (14). Thus, polyamines in the diet are among the determinants of the total body polyamine pool and may be a particularly important consideration in ... evaluating responses to pharmaceutical agents, such as inhibitors of polyamine synthesis (eg, difluoromethylornithine), which are under study in clinical trials for cancer chemoprevention. ...
This brief report describes the development of a polyamine database linked to the Fred Hutchinson Cancer Center food frequency questionnaire (FFQ). ... Of the foods from the database that were evaluated, fresh and frozen corn contain the highest levels of putrescine [per serving] (560,000 nmol/serving and 902,880 nmol/serving) and spermidine (137,682 nmol/serving and 221,111 nmol/serving), and green pea soup contains the highest concentration of spermine [per serving] (36,988 nmol/serving).
[See Table 1, Top 10 foods on the Fred Hutchinson Cancer Research Center food frequency questionnaire with the highest polyamine content](1)
See also these reports on selected polyamine contents in British and Swedish foods.
the potential protection against colorectal cancers of some nutritional factors could be associated with modifications in cellular proliferation and growth. The naturally occurring polyamines, spermine, spermidine, and putrescine, play a key role in hyperproliferation and cell migration and are involved in almost all steps of colorectal tumorigenesis. Mucosal polyamine levels, as a measurement of dysregulated hyperproliferation, have been demonstrated to be significantly associated with cancer risk and have been considered even a specific marker for neoplastic proliferation. Consequently, polyamine metabolism can be considered an attractive target for cancer chemoprevention and chemotherapy.(2)
The reduced levels of polyamines in aging tissues might explain the reported short-term apparent benefits in aging mice; that doesn't mean that the same benefits will accrue to taking it while young.This external dietary source provides a larger quantity of polyamines than the endogenous biosynthesis. The latter produces only about 1–2 nmol of putrescine per hour per gram of tissue in the most active organs. Diet can to a certain extent regulate biosynthesis of polyamines. Thus, dietary polyamines have several important roles to play in this regard; supporting a normal metabolism and maintaining optimal health as well as regulating the intracellular polyamine synthesis. These seem to be of importance for maintaining the normal growth, maturation of the intestinal tract. Since the level of polyamines decreases with age in animal organs (brain, kidney, spleen, and pancreas), it has been suggested that maintenance of polyamine level from the diet is important to keep the functioning of various organs in the elderly. On the other hand, the cell growth promoting effect may also be negative in relation to cancer development. It has been shown that increased polyamine levels are associated with increased cell proliferation as well as expression of genes affecting tumor invasion and metastasis (3).
1: Zoumas-Morse C, Rock CL, Quintana EL, Neuhouser ML, Gerner EW, Meyskens FL Jr. Development of a polyamine database for assessing dietary intake. J Am Diet Assoc. 2007 Jun;107(6):1024-7. PubMed PMID: 17524725; PubMed Central PMCID: PMC2848593.
2: Linsalata M, Russo F. Nutritional factors and polyamine metabolism in colorectal cancer. Nutrition. 2008 Apr;24(4):382-9. Epub 2008 Feb 11. Review. PubMed PMID: 18262757.
3: Atiya Ali M, Poortvliet E, Strömberg R, Yngve A. Polyamines in foods: development of a food database. Food Nutr Res. 2011 Jan 14;55. doi:
10.3402/fnr.v55i0.5572. PubMed PMID: 21249159; PubMed Central PMCID: PMC3022763.
Edited by Michael, 09 May 2011 - 04:47 PM.
Lufega 09 May 2011
think spermidine is also produced by taking SAM-e. might be interesting to see if there are any life extension studies w/ SAM-e. i've not found any... if anyone sees one, pls post it.
Maybe by increasing Creatine production ? Creatine has life extending abilities.
http://www.ergo-log....longevity2.html
Michael 09 May 2011
This is just another in a long series of instantiations of the Original Sin of biogerontology: short-lived controls.Creatine has life extending abilities.
http://www.ergo-log....longevity2.html
A normal, healthy, well-husbanded, non-genetically-fucked-up mouse (which will on av'g live ~900 days at maximum (tenth-decile survivorship) 1100 d, as is routine in the standard control groups in studies run by people who know what they're doing (Spindler, Weindruch, Miller, etc). But in report after report of 'life extension' in mice, NONE of the animals eeven live THIS long (or at best, the INTERVENTION group does).
Whether it's buggered-up mutants that die early of things of purely putative mechanistic or structural significance to 'normal' aging, or (most commonly -- resveratrol and many others) diabetic obesity from overfeeding, or malnourishment, or (as in this case) failing to keep a good lid on pathogens, you raise a colony in whicih ALL the animals are short-lived, by incompetence or by design; then if your intervention helps to partially normalize their miserably short lives, you proclaim a radical life-extension breakthru'.
Creatine improves health and survival of mice.
Bender A, Beckers J, Schneider I, Hölter SM, Haack T, Ruthsatz T, Vogt-Weisenhorn DM, Becker L, Genius J, Rujescu D, Irmler M, Mijalski T, Mader M, Quintanilla-Martinez L, Fuchs H, Gailus-Durner V, de Angelis MH, Wurst W, Schmidt J, Klopstock T.
PMID: 17416441
docTorpedo 07 Feb 2013
Droplet 11 Feb 2013
http://www.amazon.co...60565779&sr=1-1
Probably not going to help your salt levels though.
smithx 13 Feb 2013
http://www.longecity...mouse-lifespan/
There is also a message from me with a link to a site where a yogurt bacteria mix can be purchased including the strain which produces a lot of spermidine. In fact, I happen to be making a batch of that yogurt at this very moment!
I no longer recommend using FOS however, because it's not clear which bacteria can use.
mikey 27 Apr 2014
Turns out grapefruit has lots of spermidine. Anyone know how much, precisely?
Not much. I remember Turnbuckle saying something, but foods only have a tiny amount. One must supplement it for longevity effects.