19 replies to this topic

[Johan]

Which supplements are best for dealing with the seven causes of aging as described by SENS?
Is there anything you could take to help prevent, repair, get rid of, or make irrelevant:

* Cell loss / atrophy
* Glycation / AGEs
* Nuclear mutations / epimutations
* Mitochondrial mutations
* Junk outside cells
* Junk inside cells
* Death-resistant cells

From searching the forums, it seems that benfotiamine, lipoic acid and carnitine are supposed to prevent some of the glycation. But what about the other six causes? What supplements, if any, do anything about them?

Edited by Johan, 22 May 2008 - 10:18 PM.

[niner]

Which supplements are best for dealing with the seven causes of aging as described by SENS?
Is there anything you could take to help prevent, repair, get rid of, or make irrelevant:

* Cell loss / atrophy
* Glycation / AGEs
* Nuclear mutations / epimutations
* Mitochondrial mutations
* Junk outside cells
* Junk inside cells
* Death-resistant cells

From searching the forums, it seems that benfotiamine, lipoic acid and carnitine are supposed to prevent some of the glycation. But what about the other six causes? What supplements, if any, do anything about them?

Lipofuscin is a form of junk inside cells, and centrophenoxine apparently will help to mobilize it in some way. Perhaps more interesting is the action of ALCAR, which is reported to reduce lipofuscin also.

Neurosci Lett. 2001 Mar 23;301(1):1-4. Links
Acetyl-L-carnitine enhances Na(+), K(+)-ATPase glutathione-S-transferase and multiple unit activity and reduces lipid peroxidation and lipofuscin concentration in aged rat brain regions. Kaur J, Sharma D, Singh R.
Neurobiology Laboratory, School of Life Sciences, Jawaharlal Nehru University, 110 067, New Delhi, India.

This study investigated the effects of chronically administered acetyl-L-carnitine (ALC) on sodium potassium adenosine triphosphatase (Na(+), K(+)-ATPase), glutathione-S-transferase (GST), glutathione peroxidase (GPx), multiple unit activity (MUA) and lipid peroxidation (LP) and lipofuscin (LF) concentration in brain regions: cerebral cortex, hippocampus, striatum and thalamus, of 24-month-old rats. The activity of Na(+), K(+)-ATPase and GST was enhanced; that of GPx was unaffected. The MUA was increased while the levels of LP and LF were decreased. These novel data provide new additional evidence concerning the antiaging attributes of ALC.

PMID: 11239702

Indian J Med Res. 1992 Jun;96:192-8.
Lipofuscin accumulation in ageing myocardium & its removal by meclophenoxate. Patro N, Sharma SP, Patro IK.
Department of Zoology, Kurukshetra University.

A study was undertaken on the age-associated histochemical changes in the ventricular myocardium and the influence of meclophenoxate hydrochloride (MPH) on the age pigment lipofuscin. Sixty Wistar albino rats in three age-groups (3, 15 and 30 months old) were treated with meclophenoxate hydrochloride (100 mg/kg body wt/day, ip) for a period of 2-8 wk. Five animals each from the three age-groups served as controls. Various histochemical and micromorphometric studies were carried out on the myocardial tissue. A linear increase in the myocardial volume occupied by the pigment was observed with advancing age. As a result of meclophenoxate treatment, a gradual decrease in the myocardial volume occupied by the pigment was noted. After 4-6 wk treatment, the pigment bodies were found lodged into the capillary endothelium and the lumen, facilitating the removal of the pigment via blood stream. Histochemical and micromorphometric analyses of ventricular myocardium of albino rats have shown thus that deposition of the age-pigment, lipofuscin, can be accepted as an index of cellular ageing.

PMID: 1512044

Neurobiol Aging. 1993 Jul-Aug;14(4):319-30.Links
Age-related decline in multiple unit action potentials of CA3 region of rat hippocampus: correlation with lipid peroxidation and lipofuscin concentration and the effect of centrophenoxine. Sharma D, Maurya AK, Singh R.
School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.

Changes in lipid peroxidation, lipofuscin concentration, and multiple unit activity (MUA recorded in conscious animals) in the CA3 region were studied in the hippocampus of male Wistar rats aged 4, 8, 16, and 24 months. The lipid peroxidation and lipofuscin concentration were increased with age. The MUA, however, declined with age. Correlational analyses were performed for the four age groups to determine the relationship between the age-associated decline in MUA with the age-related alterations in lipid peroxidation and lipofuscin concentrations. The age-related increase in lipid peroxidation correlated positively with the age-associated increase in lipofuscin concentration. The age-related increases in lipid peroxidation and lipofuscin concentration correlated negatively with the changes in MUA. Since lipid peroxidation may affect neuronal electrophysiology, our data suggested that age-related increase in lipid peroxidation may contribute to an age-associated decline in neuronal electrical activity. Centrophenoxine effects were studied on the three above-mentioned age-associated changes in the hippocampus. The drug had no effect on all three parameters in 4- and 8-month-old rats. In 16- and 24-month-old rats, however, the drug significantly increased the MUA but concomitantly decreased lipofuscin concentration and lipid peroxidation. Correlational analyses of the data on MUA, lipid peroxidation and lipofuscin concentration from the centrophenoxine-treated animals showed that the drug-induced diminution in both lipofuscin and lipid peroxidation was significantly correlated with the drug-induced increase in MUA. The differential effect of the drug in younger (4-8 months) and older (16-24 months) animals indicated that the stimulation of MUA was clearly associated with concomitant decrease in lipid peroxidation and lipofuscin concentration.

PMID: 8367013

[Ghostrider]

Lipofuscin is a form of junk inside cells, and centrophenoxine apparently will help to mobilize it in some way. Perhaps more interesting is the action of ALCAR, which is reported to reduce lipofuscin also.

Yes niner, that is interesting. On another thread I asked if ALCAR is truely an anti-aging supplement (whether it actually reverses or impedes aging rather than just cover it up). So the example above is good to hear.

[DukeNukem]

>>> Which supplements are best for dealing with the seven causes of aging as described by SENS?

Have you read de Grey's book, Ending Aging? He's notorious for not giving much hope to supplements, and for the most part he's correct in that supps are nothing more than a very short-term life extension stepping stone. Supplements generally help at a higher level, such as reducing inflammation and reducing glycation (but not undoing existing glycation).

There are a few things I think de Grey got wrong in his book, such as the primary cause of arterialsclorosis, but these are just nitpicks. Well worth reading.

[niner]

Glycation can be (partly) reversed by alagebrium, and this medication is not more expensive than any supplements.
Especially the benefits for the cardiovascular health (reversing of glycated heart muscle proteins and arterial stiffness which is causing hypertension) are very interesting, since this is the major cause of death.

I'm not sure what you mean by not expensive... Maybe not that expensive to produce, but the only source I'm aware of is very pretty expensive compared to ordinary supplements. It also doesn't break the most common type of crosslink (glucosepane).

[Johan]

>>> Which supplements are best for dealing with the seven causes of aging as described by SENS?

Have you read de Grey's book, Ending Aging? He's notorious for not giving much hope to supplements, and for the most part he's correct in that supps are nothing more than a very short-term life extension stepping stone. Supplements generally help at a higher level, such as reducing inflammation and reducing glycation (but not undoing existing glycation).

There are a few things I think de Grey got wrong in his book, such as the primary cause of arterialsclorosis, but these are just nitpicks. Well worth reading.

Yes, I have read it, and I know he doesn't, but I figure that while we wait for SENS therapies to arrive, we might as well do what we can with supplements (and other things of course, e.g. CR).

Edited by Johan, 23 May 2008 - 07:38 AM.

[Mixter]

I also take for given that supplements can just prevent or undo a
minor amount of damage (but still significant over time), and that much
stronger intervention by SENS is needed to reverse inevitably
accumulated damage (we can just tweak the rate a bit atm).
That being said, a lot of life-extension/supplements naturally deal
with the 7 issues, here's an excerpt of the most obvious...

* Cell loss / atrophy
-> Exercise!! Including resistance training.
-> Arginine, Protein rich foods, exercise
-> Vitamin D and other telomere protecting agents
-> Vit C -> collagen, Hyaluronic acid -> ECM, MSM/Glucosamine -> Joints, etc. pp.
-> Preventing cell loss as cause of degenerative diseases otherwise

* Glycation / AGEs
-> CR
-> Carnosine
-> Metformin, Benfotiamine and the rest that was mentioned

* Death-resistant cells
* Nuclear mutations / epimutations

-> CR
-> Antioxidants, detoxifying supplements (most phytonutrients)
-> Curcumin, ECGC, genistein, and other apoptosis promotors

* Mitochondrial mutations

-> CR
-> Antioxidants
-> esp. R-Alpha-Lipoic Acid


* Junk outside cells
* Junk inside cells

-> Exercise, CR, fasting (also elevates enzyme levels + autophagy)
-> Antioxidants prevent a lot of junk from being generated
-> Inflammation reducing nutrients that prevent some junk buildup
-> Centrophenoxine (lipofuscin), maybe others


The biggest point of SENS is that most of the above is for prevention,
not reversal, and unless you achieve the impossible 100% prevention
every second, you're going to accumulate some damage that needs
to be reversed using new/foreign methods of SENS (vaccination, AGE-breakers,
new lysosomal enzymes, mtDNA transfection, stem cells...).

[niner]

Glycation can be (partly) reversed by alagebrium, and this medication is not more expensive than any supplements.
Especially the benefits for the cardiovascular health (reversing of glycated heart muscle proteins and arterial stiffness which is causing hypertension) are very interesting, since this is the major cause of death.

I'm not sure what you mean by not expensive... Maybe not that expensive to produce, but the only source I'm aware of is very pretty expensive compared to ordinary supplements. It also doesn't break the most common type of crosslink (glucosepane).

Sure it does not reverse all glycation products therefore I wrote "partly", but this is secondary important since the clinical results are more interesting and they show us an action of alagabrium which is strong enough to reverse (glycation caused) heart problems and hypertension, furthermore the stiffness of muscles, joints, bladder and so on. Future medication will be of course more effective, but you probably agree that we should use what we can get and concentrate on the most effective agents. Alagebrium is one of them.

I don`t know what you call expensive, supplements are a little bit more expensive in Germany than in the USA, but I would not call a price between 2 and 3 USD (3 USD is highest price, 2 USD are usual) for 1 gramm of Alagabrium expensive. Since you need about 400mg daily, it would be around 1 USD per day. Furthermore even a single therapy over 3 months is enough to get results.

Wow, alagebrium is sold in Germany? Is it from a reputable source? The only source I know of in America is I think $15/gram and I don't even know if it is pure. Alteon ran a couple clinical trials with it, but they were not able to show enough of a blood pressure reduction to get approval, as I recall. I would like to get some if it's from a reliable source and not insanely expensive.

[Ghostrider]

Glycation can be (partly) reversed by alagebrium, and this medication is not more expensive than any supplements.
Especially the benefits for the cardiovascular health (reversing of glycated heart muscle proteins and arterial stiffness which is causing hypertension) are very interesting, since this is the major cause of death.

I'm not sure what you mean by not expensive... Maybe not that expensive to produce, but the only source I'm aware of is very pretty expensive compared to ordinary supplements. It also doesn't break the most common type of crosslink (glucosepane).

Sure it does not reverse all glycation products therefore I wrote "partly", but this is secondary important since the clinical results are more interesting and they show us an action of alagabrium which is strong enough to reverse (glycation caused) heart problems and hypertension, furthermore the stiffness of muscles, joints, bladder and so on. Future medication will be of course more effective, but you probably agree that we should use what we can get and concentrate on the most effective agents. Alagebrium is one of them.

I don`t know what you call expensive, supplements are a little bit more expensive in Germany than in the USA, but I would not call a price between 2 and 3 USD (3 USD is highest price, 2 USD are usual) for 1 gramm of Alagabrium expensive. Since you need about 400mg daily, it would be around 1 USD per day. Furthermore even a single therapy over 3 months is enough to get results.

Wow, alagebrium is sold in Germany? Is it from a reputable source? The only source I know of in America is I think $15/gram and I don't even know if it is pure. Alteon ran a couple clinical trials with it, but they were not able to show enough of a blood pressure reduction to get approval, as I recall. I would like to get some if it's from a reliable source and not insanely expensive.

Depending on the price and purity assertion methods, I might be interested in this as well.

[caston]

One thing is that i'd like to say we need to be light hearted and intelligent about supplementation not grim and dumb. It is easy to be grim and dumb and frantic when we are dealing with aging because we think it's a race against time. If we don't slow aging enough we won't get to be immortal. Sadly many of us may have beeen hasting ourselves into more metabolic mayhem and damage than the aging itself would have caused. Using ourselves as guinea pigs and with our own theories of something as complex as metabolism.

Having said this I think that it could be worthwhile in addition to a good diet and exercise supplementing with growth factors (many found in human or animal milks) and transferrins such as lactoferrin. These can help stop bacterial infection by clinging on to available iron and lacoterrin can promote the increase of bone mineral density through encouraging osteoblasts.

I posted about lactoferrin with links to some recent research about it in the lactoferrin thread.
http://www.imminst.o...;hl=lactoferrin


As for trying to stop glycation. Consider the proteins innocent until proven glycated. You'll cause more damage to your body trying to stop glycation than the actual glycation itself would have caused. Better to wait until we can break glycated cross links then it is to waste energy trying to stop them forming at every waking moment.

Cutting down on sugar is a good idea but sugar is still important for growth and division of stem cells. When you lose your sweet tooth you lose a part of your childhood. I also disagree with avoiding fruit just because of a the fructose content. Eat plenty of good fruit and don't stress

I also think that many of us are interested in life extension because we already have longevity genes. In many of us for some reason the genes have helped shaped memes. Memes just like genes consider you disposable soma.

Edited by caston, 24 May 2008 - 09:57 AM.

[VictorBjoerk]

Sugar maybe should not be 100% restricted to growing children,but why should adults eat sugar at all?

[jayd]

Glycation can be (partly) reversed by alagebrium, and this medication is not more expensive than any supplements.
Especially the benefits for the cardiovascular health (reversing of glycated heart muscle proteins and arterial stiffness which is causing hypertension) are very interesting, since this is the major cause of death.

I'm not sure what you mean by not expensive... Maybe not that expensive to produce, but the only source I'm aware of is very pretty expensive compared to ordinary supplements. It also doesn't break the most common type of crosslink (glucosepane).

Sure it does not reverse all glycation products therefore I wrote "partly", but this is secondary important since the clinical results are more interesting and they show us an action of alagabrium which is strong enough to reverse (glycation caused) heart problems and hypertension, furthermore the stiffness of muscles, joints, bladder and so on. Future medication will be of course more effective, but you probably agree that we should use what we can get and concentrate on the most effective agents. Alagebrium is one of them.

I don`t know what you call expensive, supplements are a little bit more expensive in Germany than in the USA, but I would not call a price between 2 and 3 USD (3 USD is highest price, 2 USD are usual) for 1 gramm of Alagabrium expensive. Since you need about 400mg daily, it would be around 1 USD per day. Furthermore even a single therapy over 3 months is enough to get results.

I'm seeking a source for this. Any leads (Germany would be fine).

[PhoenixBrad]

I also take for given that supplements can just prevent or undo a
minor amount of damage (but still significant over time), and that much
stronger intervention by SENS is needed to reverse inevitably
accumulated damage (we can just tweak the rate a bit atm).
That being said, a lot of life-extension/supplements naturally deal
with the 7 issues, here's an excerpt of the most obvious...

* Cell loss / atrophy
-> Exercise!! Including resistance training.
-> Arginine, Protein rich foods, exercise
-> Vitamin D and other telomere protecting agents
-> Vit C -> collagen, Hyaluronic acid -> ECM, MSM/Glucosamine -> Joints, etc. pp.
-> Preventing cell loss as cause of degenerative diseases otherwise

* Glycation / AGEs
-> CR
-> Carnosine
-> Metformin, Benfotiamine and the rest that was mentioned

* Death-resistant cells
* Nuclear mutations / epimutations

-> CR
-> Antioxidants, detoxifying supplements (most phytonutrients)
-> Curcumin, ECGC, genistein, and other apoptosis promotors

* Mitochondrial mutations

-> CR
-> Antioxidants
-> esp. R-Alpha-Lipoic Acid


* Junk outside cells
* Junk inside cells

-> Exercise, CR, fasting (also elevates enzyme levels + autophagy)
-> Antioxidants prevent a lot of junk from being generated
-> Inflammation reducing nutrients that prevent some junk buildup
-> Centrophenoxine (lipofuscin), maybe others


The biggest point of SENS is that most of the above is for prevention,
not reversal, and unless you achieve the impossible 100% prevention
every second, you're going to accumulate some damage that needs
to be reversed using new/foreign methods of SENS (vaccination, AGE-breakers,
new lysosomal enzymes, mtDNA transfection, stem cells...).

what is CR? oh i was thinking supplement, is it caloric restriction?

Edited by PhoenixBrad, 28 July 2008 - 01:45 PM.

[health_nutty]

what is CR? oh i was thinking supplement, is it caloric restriction?

Yes, you are correct.

[kismet]

As for trying to stop glycation. Consider the proteins innocent until proven glycated. You'll cause more damage to your body trying to stop glycation than the actual glycation itself would have caused. Better to wait until we can break glycated cross links then it is to waste energy trying to stop them forming at every waking moment.

Are you implying that slowing glycation (e.g. through benfotiamine/reduced AGE intake) but not actually breaking crosslinks is a waste of time? So Michael and all others taking benfotiamine, pyridoxamine, etc. are wrong? Do you think there won't be any further studies similar to that one discussed in this thread: http://www.imminst.o...ies-t23139.html that will show efficacy of reduced AGE formation/intake?

[missminni]

what about resveratrol? nobody mentioned it, unless I missed something.

[Benedictus]

Sugar maybe should not be 100% restricted to growing children,but why should adults eat sugar at all?

Adults eat sugar because it tastes good, and it therefore makes them feel good, or feel better temporarily, which in turn has an uplifting effect in their moods, kills stress, diminishes pain and strengthens the body, improves physical resistance. Of course, but that is more than logical and applies to almost everything we can consume; You should not overconsume sugar, you should make each and every consumption a joyful experience and try to avoid routines and boredom.

Edit: Inappropriate comments removed. Discussing ideas is fine, but let's try to stay civil.

Edited by niner, 16 August 2008 - 03:59 AM.

[brokenportal]

Seven things I would take would be:



-copies of the CEL government lobby petition every where you go
-time off work to focus more time on promoting life extension
-aging to heart because eternity is a long time to spend in oblivion
-marketing classes
-biology classes
-money to the to the mprize
-a copy of "Ending Aging" to everybody you know



Take one of each of those and call me in the morning.