Insulin and IGF-1 Influences Longevity

M

Martin Levac

New Member
http://www.ncbi.nlm.nih.gov/pubmed....VDocSum

Timing requirements for insulin/IGF-1 signaling in C. elegans.
Dillin A, Crawford DK, Kenyon C.

Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94143-0448, USA.

The insulin/IGF-1 (where IGF-1 is insulin-like growth factor-1) signaling pathway influences longevity, reproduction, and diapause in many organisms. Because of the fundamental importance of this system in animal physiology, we asked when during the animal's life it is required to regulate these different processes. We find that in Caenorhabditis elegans, the pathway acts during adulthood, to relatively advanced ages, to influence aging. In contrast, it regulates diapause during development. In addition, the pathway controls longevity and reproduction independently of one another. Together our findings show that life-span regulation can be dissociated temporally from phenotypes that might seem to decrease the quality of life.
 
That's good to know if you are a dormant worm, since we are human and do not enter dormant states it means nothing.
 
<div>
(Dan Moore @ Apr. 30 2008,7:08)</div><div id="QUOTEHEAD">QUOTE</div><div id="QUOTE">That's good to know if you are a dormant worm, since we are human and do not enter dormant states it means nothing.</div>
C. elegans is used as a model organism in genetic research and other types of research. The work on longevity, insulin an IGF-1 goes on and this is just one of many papers on the subject. nkl mentioned that IGF-1 is a strong anabolic agent. IGF-1 is known to stimulate cell division. This paper shows insulin and IGF-1 to influence longevity. I would investigate the possibility that it could apply to humans.
 
<div>
(Martin Levac @ Apr. 30 2008,10:37)</div><div id="QUOTEHEAD">QUOTE</div><div id="QUOTE"><div>
(Dan Moore @ Apr. 30 2008,7:08)</div><div id="QUOTEHEAD">QUOTE</div><div id="QUOTE">That's good to know if you are a dormant worm, since we are human and do not enter dormant states it means nothing.</div>
C. elegans is used as a model organism in genetic research and other types of research. The work on longevity, insulin an IGF-1 goes on and this is just one of many papers on the subject. nkl mentioned that IGF-1 is a strong anabolic agent. IGF-1 is known to stimulate cell division. This paper shows insulin and IGF-1 to influence longevity. I would investigate the possibility that it could apply to humans.</div>
I am fully aware of that but this study was a bad choice to represent what may happen in the face of GH/IGF axis changes through insulin or caloric restriction in mammals.

There are many more substantiative pieces of research that would serve your point better. For instance Shimokawa et al 2003 showed that CR (calorie restriction) had a similar yet slightly stronger effect on longevity than GH antisense transgene overexpression in rats.

This has been backed up by the works of Andrzej Bartke's groups from SIU. You can read his new review in HORMONES 2008, 7(1):17-23
 
<div>
(Dan Moore @ Apr. 30 2008,11:22)</div><div id="QUOTEHEAD">QUOTE</div><div id="QUOTE"><div>
(Martin Levac @ Apr. 30 2008,10:37)</div><div id="QUOTEHEAD">QUOTE</div><div id="QUOTE"><div>
(Dan Moore @ Apr. 30 2008,7:08)</div><div id="QUOTEHEAD">QUOTE</div><div id="QUOTE">That's good to know if you are a dormant worm, since we are human and do not enter dormant states it means nothing.</div>
C. elegans is used as a model organism in genetic research and other types of research. The work on longevity, insulin an IGF-1 goes on and this is just one of many papers on the subject. nkl mentioned that IGF-1 is a strong anabolic agent. IGF-1 is known to stimulate cell division. This paper shows insulin and IGF-1 to influence longevity. I would investigate the possibility that it could apply to humans.</div>
I am fully aware of that but this study was a bad choice to represent what may happen in the face of GH/IGF axis changes through insulin or caloric restriction in mammals.

There are many more substantiative pieces of research that would serve your point better. For instance Shimokawa et al 2003 showed that CR (calorie restriction) had a similar yet slightly stronger effect on longevity than GH antisense transgene overexpression in rats.

This has been backed up by the works of Andrzej Bartke's groups from SIU. You can read his new review in HORMONES 2008, 7(1):17-23</div>
To paraphrase Taubes, Cynthia Kenyon is one of the few who chose to consider that there may be more to it than just caloric quantity as an agent of influence in aging rate. And so she found that glucose was such an agent independently of caloric quantity. You may be right in thinking that it's not the best example but it's a start nevertheless.

Total calories influencing aging is one notion that relies on the premise that independent macro-nutrients don't by themselves influence aging differently. Thus, the evidence that glucose, through its action on insulin and IGF-1, influences aging by itself appears to refute the first hypothesis. Granted, in order to refute it completely, we'd have to prove that one of the other two macro-nutrients (fat or protein) does not by themselves influence aging as glucose does. But again, it's a start.
 
Yes but Taubes is not recognizing the newer research that is showing that IIS (insulin-like signaling) and caloric restriction appear to be activating separate targets and show no overlap even in Caenorhabditis elegans which gives inclination of these mechanisms acting distinctively. Of course this doesn't or can not say that at some point specific signalling through dFOXO or insulin like peptides will converge downstream. But the recent research definately shows lifespan control by dietary restriction is independent of insulin-like signaling in both nematodes and flies. So as you say it's a start but I think there is a long way to go yet.
 
If the new research you speak of came out after Taubes' book, then it's understandable that he doesn't recognize it. Further, it's not Taubes that came to those conclusions, it's Cynthia Kenyon. Taubes only referred to Kenyon's work and by extension, her conclusions.

Then there's the graph which Aaron_F has so graciously provided that shows cutting carbohydrate out of the diet results in a spontaneous reduction of energy intake on the order of ~700 calories in otherwise ad libitum conditions. This suggests that even if there was no direct causative link between glucose and longevity, the link between caloric restriction and longevity remains and is thus affected by carbohydrate's ability to increase total caloric intake.
 
haha, yeah...I didn't appreciate that last statement too much.  In layman's terms, it seems like Martin just said that losing fat is all about decreasing calories

<div></div><div id="QUOTEHEAD">QUOTE</div><div id="QUOTE">This suggests that even if there was no direct causative link between glucose and longevity, the link between caloric restriction and longevity remains and is thus affected by carbohydrate's ability to increase total caloric intake</div>
 
<div>
(Martin Levac @ Apr. 30 2008,3:07)</div><div id="QUOTEHEAD">QUOTE</div><div id="QUOTE">If the new research you speak of came out after Taubes' book, then it's understandable that he doesn't recognize it. Further, it's not Taubes that came to those conclusions, it's Cynthia Kenyon. Taubes only referred to Kenyon's work and by extension, her conclusions.

Then there's the graph which Aaron_F has so graciously provided that shows cutting carbohydrate out of the diet results in a spontaneous reduction of energy intake on the order of ~700 calories in otherwise ad libitum conditions. This suggests that even if there was no direct causative link between glucose and longevity, the link between caloric restriction and longevity remains and is thus affected by carbohydrate's ability to increase total caloric intake.</div>
1. Then you should read Kenyon's newer research along with the research of Iser, Min, Wang, and Partridge who all suggest what I've said above.

2. From my recollection Taubes is still holding interviews, seminars which gives him ample time and place to mention emerging science whether opposed or in agreement with his stance in the book. If he is truly the &quot;science&quot; writer that he is given credit for being then that shouldn't be an issue for him.

That is still a far cry from the ascertion that insulin or insulin signalling is the truly causitive link. Which I believe to be your purpose in posting that study, I could be wrong there of course and your purpose was far less sinister
wink.gif
. Plus it also adds in the reasonable corollary that reduction of any macronutrient, creating a sufficient caloric deficit, would do the same. Or as you put it, any increase in any macro that would throw one over the caloric intake ceiling for this effect would do the same.

Lastly and to show I'm not a bad guy, is ....... as of today all of this is based on what has been seen in lesser animals and what may or may not happen in humans could be a whole another discussion.
 
<div>
(Dan Moore @ Apr. 30 2008,7:04)</div><div id="QUOTEHEAD">QUOTE</div><div id="QUOTE">...
1. Then you should read Kenyon's newer research along with the research of Iser, Min, Wang, and Partridge who all suggest what I've said above.as of today all of this is based on what has been seen in lesser animals and what may or may not happen in humans could be a whole another discussion.
...</div>
I may just do that.

From GCBC p. 223:
&quot;As Kenyon tells it, the day she realized that glucose shortened the lives of her worms, she decided to restrict her own consumption of carbohydrates to a bare minimum. She lost thirty pounds, she says; her blood pressure, triglycerides, and blood-sugar levels all dropped; and her HDL increased. Kenyon recognizes her experience as anecdotal, but it certainly influenced her suspicion that carbohydrates would also cause chronic disease in humans through their effect on insulin and insulin-like growth factor.&quot;


As far as I know, insulin and IGF-1 is extremely similar from one species to another. We extract insulin from sheep and inject it in humans. It does the same job. I don't see why insulin's function should be different from one species to the next.
 
<div>
(Martin Levac @ Apr. 30 2008,7:29)</div><div id="QUOTEHEAD">QUOTE</div><div id="QUOTE">As far as I know, insulin and IGF-1 is extremely similar from one species to another. We extract insulin from sheep and inject it in humans. It does the same job. I don't see why insulin's function should be different from one species to the next.</div>
Insulin? Possibly

IGF-1 maybe not. IGF is not insulin per se it is a growth factor with insulin &quot;like&quot; properties and there are a various amounts of IGF with different physiological roles and actions. I'm going strictly from memory here so don't quote me but if I recall human IGF-1 alone has about 7 or so various isoforms while rats have about 14. If someone knows the exact isoforms they can correct me if I'm wrong. So when speaking of IGF are we speaking about 1a, Ie, IIa, IIe, or so on.

I have no clue how many isoforms nematodes or fruit flies have.

So we have to be sure we are comparing apples to apples and oranges to oranges. And be sure what is seen in these other animals can even occur in humans.

Also what is occurring through various peptides IE insulin like peptide 2 versus 5 may be vastly different and their downstream activation targets may be different as well.

<div></div><div id="QUOTEHEAD">QUOTE</div><div id="QUOTE">I may just do that.</div>Good I think you should and I think this was one of Aaron's points as well. Reading what other's have wrote is fine but then again sometimes it's better not to take anyone's word for it and go learn it yourself. No matter how gruff Aaron comes off remember that this is his job, he is a clinical researcher and a dang good one I might add. His understanding of clinical research methodology far surpasses mine but then again it should.
 
You must log in or register to reply here.
Back
Top