LONGECITY

Suppose I have an experimental organism and that intevention A increases the lifspan by 30% while intervention B increases the lifespan by 25%.
If you combine this two interventions would you then say that the lifespan increase would be 1.3*1.25=1.625 => 62.5% or 1.3+1.25 =1.55 => 55%.
In general would you consider lifespan interventions to be additive or multiplicative?

By the way I found a database of antiaging interventions:

http://sageke.scienc...org/cgi/genesdb

..and a bunch of .pdf´s

http://sageke.scienc...scifeatured.dtl

In general would you consider lifespan interventions to be additive or multiplicative?

Purely guessing, I would think that they would be additive but with diminishing returns.

I would be inclined to say VERY diminishing returns, with current ways of extending life.

I have yet to see what happens when you survive heart disease, cancer, organ failure, and brain degeneration. These are what my supplement regime targets.

it will always depend.

sometimes A and B are additive... meaning they probably work via 'independent' molecular pathways.

sometimes there is no cumulative effect at all: B will not increase lifespan further... meaning the two affect probably the same molecular pathway.

i've never seen an example with the multiplication of life span extension figures... it either adds to... or does nothing at all...or even eliminates the effect!

correct?

This area of research is totally, ridiculously neglected, especially in higher animals. Great question. Should have been systematically asked long ago in the lab, imo. For a start, this is an inspiring experiment in worms.

Hey! that's our lab!! [lol]

This area of research is totally, ridiculously neglected, especially in higher animals. Great question. Should have been systematically asked long ago in the lab, imo. For a start, this is an inspiring experiment in worms.

John, could you make the argument that independent pathways are more likely to be cumulative if in fact that is what the regimen targets?

for instance, if you targeted increasing the cell receptivity with metformin, used NtBHA for mitochindrial upregulation and partial repair, and possibly used amminoguanidine and benfotiamine for reducing crosslinks, that would technically be three seperate pathways? or am I mistaken?

Hi Geert,
Cool, are you at imminst because an interest in human applications of what you do? Is there anything you can tell us about what you do there without breaching some sort of confidentiality?

Karo,
I know nothing of these molecules. You are probably more qualified to judge your argument than I am.

It can be important to distinguish between interventions are targeting a specific damage-type directly ("mitochondrial repair"), as opposed to interventions targeting a "longevity master pathway" which affects the rates of accumulation and repair of many damage types (such as caloric restriction, and what else they did to the worms).

The former will tend to give diminishing returns, because multiple damage-types will be equally limiting (due to lack of pressure to evolve damage-repair beyond whatever else is limiting), unless of course you manage to remove all limiting damage-types simultaneously, when the gain will theoretically be huge.

The latter can do anything, bound only by the constrains Geert put on the table.

Hey! that's our lab!!

Wow, it's really weird at times to see how small the internet can make the world appear.

I believe it varies. I would make a conservative guess and say that it's less than additive, and probably contains overlap. It may even be negative, only experiment can tell.

But generally, yes, there is a great need for research into various overlapping of anti-aging and rejuvenative healing mechanisms.

As an example, aren't the same mechanisms of anti-aging gene stimulation triggered by both red wine and caloric restriction, and they don't add or multiply at all?

I do think they would multiply, however, if they are assuredly different mechanisms of aging, not linked together (or related) in the slightest.

John, could you make the argument that independent pathways are more likely to be cumulative if in fact that is what the regimen targets?

Considering that the "aging" process is multifactorial, I would say yes to the above questions.

I think it is also important to refer to aging as both "intrinsic" and "extrinsic". Most of the changes seen with "extrinsic" aging, IMO are not the result of aging per se.

it will always depend.

sometimes A and B are additive... meaning they probably work via 'independent' molecular pathways.

sometimes there is no cumulative effect at all: B will not increase lifespan further... meaning the two affect probably the same molecular pathway.

i've never seen an example with the multiplication of life span extension figures... it either adds to... or does nothing at all...or even eliminates the effect!

correct?

but each individual will take their own time to discover.

I'm very much interested to know about the example of the multiplication of life span extension figures, can u pls let me know

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s.k
Edited by shepard, 19 January 2009 - 04:38 PM.
Removed Spam URL

Hi,
I dont know much knowledge about antiaging interventions,i visit the link which you are provided,the website is more useful for me to know about antiaging interventions .About my opinion lifespan interventions to be additive .
Thanks for sharing the informations.......

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RAMYA
Edited by shepard, 19 January 2009 - 04:38 PM.
Removed Spam URL

While A + B may be additive. Some here are doing A + B + C+ D . . . + Z. And an accumulation of antiaging interventions may cause accelerated aging for all we know.

Usually too much of anything is not good for you. For example, too much water will kill you, too much exercise will weaken you, too much fat, protein or carbs would not be optimal. It could be the same with antiaging interventions. If someone is taking 20 or more supplements, this is probably extreme. Is it too much, who knows?

So if you follow the theory that too much of anythingwill likely harm you and you believe it, then you have to wonder if many here are harming themselves. Imminst probably does have some of the highest supplement users (myself included).

In general would you consider lifespan interventions to be additive or multiplicative?

Purely guessing, I would think that they would be additive but with diminishing returns.

I would be inclined to say VERY diminishing returns, with current ways of extending life.

I have yet to see what happens when you survive heart disease, cancer, organ failure, and brain degeneration. These are what my supplement regime targets.

I guess that by tuning interventions that currently bring 30% more life in mice we could in fact more than double the lifespan.

In worms (C elegans), a 10 fold life extension is obtained with some age-1 mutants:

Ayyadevara S et al. Remarkable longevity and stress resistance of nematode PI3K-null mutants. Aging Cell. 2008 Jan;7(1):13-22 [pubmed astract]

Brief explanation: so far several mutations of the age-1 gene had been studied [linked to the IGF-1 pathway, where lives where also extended in fruit flies and mice], extending lifespan by up to 2.6 folds... in the first generation of mutants. Ayyadevara S et al observed that the next generations (that do not have an additional mutation, but are not "age-1 contamined" by their parents) live A LOT longer.

I found a free version of the pdf on the internet: http://www.uams.edu/.../aging_cell.pdf Read it! The paper talks about other exemples of lifespan changes with combinations or slight modifications of experiments, in worms, flies and mice.

http://uwaging.org/genesdb/ is a list of Interventions

A thought on the Cumulative effect of antiaging interventions is that different interventions affect different cxhemical compartments A fat soluble chemical drug plus a water soluble chemical drug plus a nanomolar active cytokine messenger plus an iRNA drug could affect completely different compartments