21 replies to this topic

[Mind]

Spindler's vast armies of lab mice prove there is hardly any supplement that extends lifespan....in mice.

This should not be too much of a surprise for people who have followed Spindler's research through the years, or for those who have enough temerity (calling Opales, where are you?) to acknowledge epidemiological evidence showing no (or negative) effects from several vitamin studies (with acknowledgement to the flaws).

And Spindler DOES know how to extend the lifespans of mice, being the inaugural winner of the Methuselah Mouse Prize.

Spindler tested over 60 supplements, even some of our (the Longecity community's) favorites. Blueberries? No lifespan extension...in mice. Ortho-core? Doesn't extend lifespan....in mice. LEF mix? Doesn't work (in mice). Krill oil? Doesn't work (in mice).

Metformin? Maybe a small effect (in mice).

And just to flip the coin. Spindler frequently mentions how CR works so well in mice. In fact CR is SPECTACULAR at extending the lifespan....of mice (and many other species). In primates? Not so great.

This is good research (in mice). Everyone should take notice. I still think that a low dose quality multivitamin (like Vimmortal, which is currently out of production, sorry), is probably, at least slightly beneficial, because we are talking about ESSENTIAL nutrients. Dr. Ames'; triage theory of aging does hold a little weight with me. However, expensive multi's with over-doses of many vitamins and minerals, increasingly look like a very poor investment.

I suspect that Longecity members are squaring their healthspan curve by careful supplementation and through various other lifestyle modifications (CR, exercise, diet), but if you are spending big bucks on supplements, maybe you should reconsider. Especially when acknowledging the tragic lack of funding for real rejuvenation research.

[nupi]

How about optimizing health within the bounds of longevity we currently have? That in itself seems like a worthy goal to me (in fact, I'd prefer to have a shorter, good life to a drawn out, bad one). And several supplements that do not seem enhance mice longevity at least seem to have positive influence on key biomarkers (e.g. fish oil) and some have at least some evidence of nootropic or mental benefits (although few if any supplements ever made a real difference for me there, despite the studies showing some of them being on par with many prescription drugs).

[niner]

I think there's little doubt that we are squaring the curve. We're also getting immediate relief from some symptoms. We're even, of late, reversing some symptoms of aging. All of this is certainly good enough reason to pay attention to supplements and drugs, and to use them appropriately.

There's a long-standing belief in the immortality community that interventions that square the curve are somehow "enemies" of the interventions that we really want, which would reverse the damage of aging. I guess the idea is that they are depriving SENS et al. of money that could be used for needed research, or maybe relieving people of some of the desperation that might move them to become more active in the movement. I think this is tremendously misguided for a number of reasons.

Those in the movement are often baffled as to why vastly more people won't support age-reversal research. Do they want to age and die? No, they don't want to, the problem is that they don't believe that anything can be done to change aging, because they've never seen it. If we show them robust curve squaring and a little bit of reversal of aging, they will be a lot more likely to accept that we could do serious rejuvenation, and would be a lot more likely to support research toward it.

Curve squaring is a population statistic. It has no relevance to an individual. If an individual "squares his own curve", he lives longer, and that's a big deal. To dismiss that as "Just curve squaring" is missing the point, if you ask me. If someone expects to achieve immortality in their own lifetime, and they are at the same time devaluing curve squaring, then they are making a miscalculation that will probably be fatal. The problem is that we aren't there yet, and technology seldom moves as fast as we want it to. Anyone who is avoiding the tools we have now (lifestyle and substances) that may add ten or twenty years to their personal lifespan may well die waiting for damage reversal technology to become available.

Although the experiment will probably happen soon, Spindler and the rest of the ITP have not yet tested c60-oo. I don't think any of the interventions that they've tested to date had the sort of pre-existing evidence that we have with c60-oo: A substantial, and frankly unprecedented increase in lifespan in a genetically normal mammal.

[Mind]

I am all for healthspan curve-squaring, my point was that some people take the "supplement thing" overboard and it is most likely a mis-allocation of resources.

[aaaaaaal]

What about Telomerase?:

Telomerase therapy dramatically extends mouse lifespan

I agree with you Mind that everyone should take a low dose multi-vitamin supplement.

Edited by jorgepl22, 15 December 2012 - 04:08 PM.

[Dorian Grey]

Regarding calorie restriction working well in test animals with short lifespan but faltering in longer lived animals...

Is it really the CR, or perhaps reduced iron loading that makes the difference?

Short lived test animals may benefit from CR through reduced iron accumulation, whereas longer lived animals may accumulate iron regardless of starvation diets due to the sheer length of their lives.

Can Humans Live Longer? (Bill Sardi) http://www.lewrockwe...ig/sardi10.html

Calorie or iron restriction?

"Studies of fruit flies (Drosophila melanogaster) may help to understand the supremacy of iron control in the aging process. Fruit flies are often used in aging studies because of their short life span, maybe 50-70 days. Insects have inborn mechanisms to control iron similar to humans. Insects control iron by iron-binding proteins (ferritin, transferrin). Excessive iron has been found to be the initiator of aging in fruit flies.⁹

Researchers at the University of Texas Health Science Center in San Antonio, Texas, measured the aging rate of mice at 6, 12 and 24 months by determining the level of oxidation (rusting of tissues) in various organs. The more food these animals consumed the more iron that accumulated in their tissues and the greater the oxidation (aging). As early as 1985 researchers proposed that the rate of age-related iron accumulation correlates with the life span of some species. The accumulation of iron in these rodents did not occur till growth had been completed. After that time iron levels increased in the liver by 140 percent and the kidney by 44 percent. The liver and brain experience the greatest iron buildup with advancing age.

An iron-restricted diet minimized the oxidation levels in the liver, kidney and brain with advancing age. The lifespan of the fruit fly has been found to be proportional to the iron content in the diet. The life span of humans has been correlated with mice and the fruit fly. Consumption of tea extracts, which bind iron and inhibit its absorption, has been found to inhibit the age-related accumulation of iron and prolong life in the fruit fly by as much as 21 percent.¹¹ So calorie restriction may not be the only way to prolong human life."

Get Thee To A Blood Bank!

Edited by synesthesia, 15 December 2012 - 05:21 PM.

[niner]

What about Telomerase?: Telomerase therapy dramatically extends mouse lifespan

Well, this particular case is gene therapy rather than a supplement, but it suggests that if we can lengthen telomeres sufficiently, in the right tissues, that we might see some life extension from it. Since we now have compounds that have been shown to activate telomerase and lengthen telomeres, we actually have an example of true regenerative medicine; the reversal of some of the damage of aging. It comes in the form of a supplement, too. It doesn't work all that well yet, though the improvements are clinically measurable. Further advances in this area will be nice to see.

Is it really the CR, or perhaps reduced iron loading that makes the difference?

I think there's a lot more to CR than just iron restriction, although iron restriction probably helps at least a little. Do we have any examples of humans or other mammals showing significant life extension from iron restriction alone? In the case of vegans, there's iron restriction but there might also be protein or methionine restriction, along with altered intake of various other nutrients. Since CRON involves Optimal Nutrition along with CR, you'd think that CRONies would be targeting the optimal iron (and copper, etc) level, along with all the other nutrients, so they would probably be the people to ask.

[Dorian Grey]

"Do we have any examples of humans or other mammals showing significant life extension from iron restriction alone?"

Not a lot of iron restrictors out there (yet!), but some of our own species (females) accumulate iron more slowly then others (men) due to menstruation and blood loss from child bearing and live on average half a decade longer throughout all races countries and cultures.

It's not the estrogen... http://www.ncbi.nlm....pubmed/16595027 "Although it was believed estrogen conferred cardiac protection and reduced the incidence of myocardial ischemic events and cerebrovascular accidents, the more recent literature indicates that this is not true and that HRT users have a higher risk of cardiac and cerebral events."

Men who mimic this blood loss through donation or bloodletting seem to benefit from this practice.

http://www.ncbi.nlm....ed?term=9737556


Donation of blood is associated with reduced risk of myocardial infarction. The Kuopio Ischaemic Heart Disease Risk Factor Study.


"In a Cox proportional hazards model adjusting for age, examination years and all other predictive coronary disease risk factors, blood donors had a 88% reduced risk (relative hazard = 0.12, 95% confidence interval 0.02-0.86, p = 0.035) of acute myocardial infarction, compared with non-blood donors."

Heart attacks in females are almost unheard of until menstruation has ceased for 10 years or so and iron/ferritin levels rise to unhealthy levels.

Cancer also has an iron connection...

http://onlinelibrary...560312/abstract

Moderate elevation of body iron level and increased risk of cancer occurrence and death

"There is evidence, in this cohort, of elevated cancer risk in those with moderately elevated iron level. This pattern was seen in women as well as in men"

Alzheimers as well...

http://www.ncbi.nlm....les/PMC2732125/


Getting the iron out: Phlebotomy for Alzheimer’s disease?


"This communication explores the temporal link between the age-associated increase in body iron stores and the age-related incidence of Alzheimer’s disease (AD), the most prevalent cause of senile dementia. Body iron stores that increase with age could be pivotal to AD pathogenesis and progression. Increased stored iron is associated with common medical conditions such as diabetes and vascular disease that increase risk for development of AD. Increased stored iron could also promote oxidative stress/free radical damage in vulnerable neurons, a critical early change in AD. A ferrocentric model of AD described here forms the basis of a rational, easily testable experimental therapeutic approach for AD, which if successful, would be both widely applicable and inexpensive. Clinical studies have shown that calibrated phlebotomy is an effective way to reduce stored iron safely and predictably without causing anemia. We hypothesize that reducing stored iron by calibrated phlebotomy to avoid iron deficiency will improve cerebrovascular function, slow neurodegenerative change, and improve cognitive and behavioral functions in AD. The hypothesis is eminently testable as iron reduction therapy is useful for chronic diseases associated with iron excess such as nonalcoholic steatohepatitis (NASH), atherosclerosis, hereditary hemochromatosis and thalassemia. Testing this hypothesis could provide valuable insight into the causation of AD and suggest novel preventive and treatment strategies."

Get Thee To A Blood Bank!

Edited by synesthesia, 15 December 2012 - 06:25 PM.

[Kevnzworld]

Metformin reduces iron by improving insulin sensitivity.
"Increased body iron stores of obese women with polycystic ovary syndrome are a consequence of insulin resistance and hyperinsulinism and are not a result of reduced menstrual losses.
serum ferritin levels decreased at 12 and 24 weeks of treatment only with metformin, in association with a marked increase in insulin sensitivity.
http://www.ncbi.nlm....pubmed/17536071

Its interesting that Spindler found that metformin semi significantly extended lifespan with his strain of mice, however, his partner in a new study found that Metformin increased lifespan of a different strain of mice significantly. ( from the video posted by Mind )

Maybe another reason to take Metformin, and avoid red meat.

[Mind]

Of course Iron restriction can be taken too far and be dangerous, however, I try to keep my iron levels on the lowish side through blood donation.

Another good Longecity discussion on Iron, one which Niner started.

[Jembe]

nupi: that's what I'm counting on. Any longevity effects in addition to that is a bonus. Magnesium has made me fall asleep easier, zinc and B-complex has reduced my acne and given me smoother skin, CoQ10 has given me more energy and reduced post-workout fatigue etc.

[1kgcoffee]

There was a study done a few years ago showing CR-like, life extending effects on mice from a panel of antioxidant supplements.
The problem with this research is the use of single supplements, in wrong form, less than ideal dosages, in the wrong conditions. For example, did the mice recieve fresh blueberries, or were they force fed a freeze dried extract in stressful prison like conditions? What was their diet like? Were they fed a high sugar diet, effectively turning off any longevity genes that may have been activated by the supplements? I wonder if their bodies were soaked in cortisol from the experimental conditions.

I'm curious how a mouse on a longecity style regimen of 5-20 supplements, eating a healthy low carb diet, with lots of exercise and low stress levels would do.

[Kevnzworld]

We haven't seen the study itself yet. We don't know methods or doses. We haven't seen the raw data and lifespan tables.
I remember a rat study from the past ( I have to find it later ), that found that green tea extract, resveratrol and curcumin did not " significantly " extend longevity over control. However, actual analysis of the data told a completely different story.
Spindler does seem to have a bias towards CR afterall.

[Dorian Grey]

Regarding keeping iron levels on the "lowish side", it should be noted the upper limits for ferritin (stored iron) are set outrageously high by many labs.

I've seen 200 for females and 300 for males set as the normal high for ferritin, but newer thinking is anything close to or above triple digits for ferritin may be less than optimal for optimal health.

Look Here: http://www.irondisor...org/iron-tests/
(scroll down to Serum Ferritin SF)


"Serum ferritin measurements range from about 15–200 ng/ml for women and 20–300 ng/ml for men. Although laboratory ranges vary, most are close to these values. Approximately 95% of the population will fall within “normal” population range simply because ranges are calculated using standard statistical methodology. Except for the lower ends of these ranges, which can predict anemia or iron deficiency anemia, the ranges per se do not define optimal or even healthy iron levels.

Optimal SF ranges for men and women are 25 – 75 ng/ml.

Individuals with risk factors for diabetes, cardiovascular diseases, stoke, liver diseases and cancer face amplified risks proportional to the amount of stored body iron over and above the optimal range.

Numerous medical research studies have demonstrated that serum ferritin above 100 ng/ml has been associated with decreased cardio vascular fitness and increased incidences of: atherosclerosis, type 2 diabetes, cancer gout and accelerated aging including osteoporosis and sarcopenia (muscle wasting) due to oxidative stress. Fortunately this does not pertain to everyone; ferritin levels and stored iron can remain safely contained, even when ferritin exceeds 150 ng/ml, if the body’s natural antioxidant defenses are working properly (see section on GGT)".

Get Thee To A Blood Bank!

Edited by synesthesia, 15 December 2012 - 07:40 PM.

[Mind]

We haven't seen the study itself yet. We don't know methods or doses. We haven't seen the raw data and lifespan tables.
I remember a rat study from the past ( I have to find it later ), that found that green tea extract, resveratrol and curcumin did not " significantly " extend longevity over control. However, actual analysis of the data told a completely different story.
Spindler does seem to have a bias towards CR afterall.

You can see a few of the lifespan tables in the video I linked to in the first post.

There was a study done a few years ago showing CR-like, life extending effects on mice from a panel of antioxidant supplements.
The problem with this research is the use of single supplements, in wrong form, less than ideal dosages, in the wrong conditions. For example, did the mice recieve fresh blueberries, or were they force fed a freeze dried extract in stressful prison like conditions? What was their diet like? Were they fed a high sugar diet, effectively turning off any longevity genes that may have been activated by the supplements? I wonder if their bodies were soaked in cortisol from the experimental conditions.

I'm curious how a mouse on a longecity style regimen of 5-20 supplements, eating a healthy low carb diet, with lots of exercise and low stress levels would do.

These are all valid points. However, I am still a little disappointed that there were no lifespan effects, even with top quality supps that have numerous vital nutrients like Orthocore and the LEF mix.

[Kevnzworld]

Regarding life extension in mice and what is " statistically significant "
I want to remind everyone that a yet to be published paper by Spindler with a different strain of mice did find Metformin significantly extended lifespan.

Remember this study? "Evaluation of Resveratrol, Green Tea Extract, Curcumin, Oxaloacetic Acid, and Medium-Chain Triglyceride Oil on Life Span of Genetically Heterogeneous Mice "
http://resveratrolce...ngevitStudy.pdf
It concluded " None of these five agents had a statistically significant effect on life span of male or female mice,"
Yet the data told a different story. Here is the chart.

Table 1 Medium Survival for each Intervention pooled across sites for each gender.

Group Males Females

Control 786 (742-826) 866 (832- 891)
Curcumin 808 (744-838) 905 (836-933)
Green Tea 822 (769-880) 923 (887-939 )
Oxaloacetic acid 819 (756-857) 889 (859-937)
Resveratrol 813 (763-863) 907 (871-938)

The survival numbers are clearly better for the supplemented animals, but yet not "statistically significant ".
One quote from the study:
" Similarly, it was reported that male C57BL/6NNia mice, fed TC the primary blood metabolite of
curcumin, at a concentration of 2000 ppm in diet starting at 13 months, had an 11.7% greater mean life span as compared with mice fed the control diet, "
In the female mice group that consumed green tea extract or resveratrol, ALL of the mice outlived the medium survival of the control group.
The evidence above though not game changing still supports the efficacy of supplementing these nutrients.

Edited by Kevnzworld, 15 December 2012 - 11:01 PM.

[YOLF]

What is the effect of the loss of blood stem cells over time from regular (at acceptable intervals) blood donation? I've always thought that I might be giving away my stem cells and shortening my life by donating.

[niner]

All accounts seem to be that you are lengthening your life by donating blood rather than shortening it. The primary hypothesis is that you are offloading iron, which is bad in excess. I've never heard that stem cells are depleted this way. Haematopoietic stem cells reproduce, which is why HSC (bone marrow) transplantation works. As we speak, my brother in law, who has (or had, I hope) Mantle Cell Lymphoma, is in the long process of reconstituting his entire haematopoietic system from a small number of stem cells donated by his brother. Prior to the transplant, he was given drugs that killed all of his HSCs.

[Nootropic Cat]

Were any of us ever really expecting to see much increase in max lifespan from diet or supplements? Surely squaring the curve was always the goal with those strategies, and something more radical will require a more radical method.

[Kevnzworld]

Were any of us ever really expecting to see much increase in max lifespan from diet or supplements? Surely squaring the curve was always the goal with those strategies, and something more radical will require a more radical method.

Hey, I'll take having my curve squared if it means extending my healthy active life well beyond what it would have been without supplementation and diet. If you look at the mouse study I posted a few posts back, supplemented animals all did better than controls. There may be a synergistic effect by taking all of them vs what any single one demonstrated. If something radical is eventually discovered , I want to live long enough to benefit from it.
Who knows, maybe C60 is that substance.....

Edited by Kevnzworld, 26 December 2012 - 07:03 AM.

[Nootropic Cat]

Yup, agree with all of that. I was just sort of wondering who this thread was aimed at (no offence Mind). I think we're mostly pretty non-delusional on these boards.

Edited by TripleHelix, 26 December 2012 - 07:14 AM.

[Mind]

Yup, agree with all of that. I was just sort of wondering who this thread was aimed at (no offence Mind). I think we're mostly pretty non-delusional on these boards.

The is no shortage of hype surrounding supplements (for direct life extension), been going on for decades now. Hopefully this research helps people remain grounded and realistic.