266 replies to this topic

[niner]

I don't see how an experiment may prove or disprove my observation of a simple, plainly seen fact that we don't age --i.e. don't accumulate damage-- while we're young. This is so obvious that it even sounds like an oxymoron.

And I am still to see a study that shows "damage accumulation" (beyond passing side-effects of an illness) in a young cohort. Not to go too far, the study linked by corb just above compares people under 30 with those over 60 and confirms that regenerative capacity is impaired in old age (>60). But where is the study that shows that a similar decline takes place in young groups, say, 20-25 compared to 25-30? This is what's claimed by the accumulating damage theory. Based on what?

So you're still trying to see molecular damage using only your eyes? Good luck with that. I posted a paper that had people as young as 16, but you weren't impressed with it. Photodamage on facial skin has been detected in pre-schoolers, but I'm not really feeling like digging up the reference, since you seem to have made up your mind.

[Danail Bulgaria]

 

Lol. Not exactly. Induced pluripotent cells are usual cells (somatic cells, non stem cells), that are turned into stem cells.

 

What I ment is to take an old an inactive stem cell, recover it, and implant it back.

 

 

Fibroblasts typically, not just any random cells - and fibroblasts are not that remote from stem cells.
And yes senescent fibroblasts as well.

But I feel like what you're asking is whether someone can do it in vivo to your existing stem cell populations.

Well seeing how they're tumorigenic in culture... you see how things would go, I believe.

 

There were experiments with mice, back when telomerase was the hype. They made mutant mice that were producing telomerase and basically had stem cells that would never become senescent. They all died from cancer.

 

Ah which reminds me, all the mice in the GDF11 experiments died as well. In a timely manner, no life extension was recorded.

 

 

I'm not talking about blasting telomerase to cells in vivo. Nor about forcing the damaged cells to multiply. I am talking about taking a single senescent stem cell (First in vivo stage) then recover its damage in a lab (First in vitro stage). Being the stem cell repaired should eliminate the chance of becoming a cancer cell. And implant it back (second in vivo stage). This worths trying according to me.
 

[LeeYa]

 However, there is zero evidence that aging factors alone can fix glycation damage, or eliminate senescent zombie cells, or unclog lysosomes that are full of indigestible junk. That is the kind of thing that SENS is trying to fix.

 

 

Good points!

 

-According to glycation: If there would be no endogenous mechanims to get rid of it, how do you think that it is possible to lower HbA1c with Metformin in people with diabetis mellitus? Furthermore, there are tons of ingested AGEs every day. Lysosomes must be overloaded even bevor you reach school age, right?

Recently, there are even counterintuitive findings that indicate a benefit from AGEs: http://www.sciencedi...53155651400360X

(eventually a hormetic reaction, in terms of a reactivation of repair mechanisms?)
 

-Senescent zombie cells should be removed by apoptosis or by digestion from macrophages, if endogenous repair mechanisms return to work.

[corb]

 

 However, there is zero evidence that aging factors alone can fix glycation damage, or eliminate senescent zombie cells, or unclog lysosomes that are full of indigestible junk. That is the kind of thing that SENS is trying to fix.

 

 

Good points!

 

-According to glycation: If there would be no endogenous mechanims to get rid of it, how do you think that it is possible to lower HbA1c with Metformin in people with diabetis mellitus? Furthermore, there are tons of ingested AGEs every day. Lysosomes must be overloaded even bevor you reach school age, right?

Recently, there are even counterintuitive findings that indicate a benefit from AGEs: http://www.sciencedi...53155651400360X

(eventually a hormetic reaction, in terms of a reactivation of repair mechanisms?)
 

-Senescent zombie cells should be removed by apoptosis or by digestion from macrophages, if endogenous repair mechanisms return to work.

 

 

Of course the body has a mechanism for clearing out AGEs. But it's imperfect. No youthful signaling can change that, it's imperfect in the young as well - so once you have a build up of AGEs especially in the extracellular matrix the only way to clear them out - is to clear them out. And that's a fact, not a theory.

 

Senescent cells can be removed by your system sure. But it's also been proven by experiment that removing them reverses some aging pathologies so either way of doing it is valid.

[LeeYa]

Of course the body has a mechanism for clearing out AGEs. But it's imperfect. No youthful signaling can change that, it's imperfect in the young as well - so once you have a build up of AGEs especially in the extracellular matrix the only way to clear them out - is to clear them out. And that's a fact, not a theory.

 

Senescent cells can be removed by your system sure. But it's also been proven by experiment that removing them reverses some aging pathologies so either way of doing it is valid.

 

 

Hello corb, thanks for your reply!

 

So, imperfect clearance of AGEs is a primary driver of aging, according to your opinion?

 

Well, then we should expect AGE-accumulation in long lasting connective tissue in a linear time dependent fashion (and maybe an additional acceleration of AGE-accumulation in case of glucose intolerance).

 

In contrast, according to xEvas hypothesis we would predict roughly the same amount of AGEs in young persons, indicating an equilibirum between AGE accumulation and AGE clearance, followed by a significant increase of AGEs due to the proposed shutdown of Repair.

 

Is there a difference in the amount of AGEs in, let's say, a 10 year old person in comparison to a 20 year old person? Any data?

Edited by LeeYa, 20 January 2015 - 01:17 PM.

[Kalliste]

 

The simplest way to test xEvas hypothesis is still to produce repair therapies.

I don't see how an experiment may prove or disprove my observation of a simple, plainly seen fact that we don't age --i.e. don't accumulate damage-- while we're young. This is so obvious that it even sounds like an oxymoron.

And I am still to see a study that shows "damage accumulation" (beyond passing side-effects of an illness) in a young cohort. Not to go too far, the study linked by corb just above compares people under 30 with those over 60 and confirms that regenerative capacity is impaired in old age (>60). But where is the study that shows that a similar decline takes place in young groups, say, 20-25 compared to 25-30? This is what's claimed by the accumulating damage theory. Based on what?

 

 

Frankly I believe that we start to accumulate damage very early on. The evidence is overwhelming for skin cancer, for instance. The simplest thing to do is to design repair treatments in animals and see if they work. That has already been done, with good evidence re senscent cells.

http://www.scienceda...50115134624.htm

 

I think you are obsessed with fasting and stuff like that. It's probably a great idea to do, to increase probability of reaching LEV, but I feel certain that you will die anyway.

Edited by Cosmicalstorm, 20 January 2015 - 01:41 PM.

[corb]

Hello corb, thanks for your reply!

 

So, imperfect clearance of AGEs is a primary driver of aging, according to your opinion?

 

Well, then we should expect AGE-accumulation in long lasting connective tissue in a linear time dependent fashion (and maybe an additional acceleration of AGE-accumulation in case of glucose intolerance).

 

In contrast, according to xEvas hypothesis we would predict roughly the same amount of AGEs in young persons, indicating an equilibirum between AGE accumulation and AGE clearance, followed by a significant increase of AGEs due to the proposed shutdown of Repair.

 

Is there a difference in the amount of AGEs in, let's say, a 10 year old person in comparison to a 20 year old person? Any data?

 

 

I never said it's a primary driver of aging. But it's an accumulation of damage that happens and can't be halted or removed with efficiency by your system. So once you have enough AGEs, they are there to stay, unless it's handled directly - which unfortunately for the moment it can't, because all the AGE breakers that work on the extremely robust extracellular AGEs are much more damaging in vivo than the AGEs themselves - which is also one possible explanation why some AGEs accumulate, a mechanism to remove them completely would have been too damaging to your body.

 

 

One mechanism that may influence the quality of skeletal muscle proteins, and explain the age-related decline in contractility, is protein damage. Advanced glycation end-products (AGE) in vivo are useful biomarkers of damage. In this study, comparison of extensor digitorum longus (EDL) muscles from young (8 months), old (33 months), and very old (36 months) Fischer 344 Brown Norway F1 (F344BNF1) hybrid rats shows that muscles from the very old rats have a significantly higher percentage of myofibers that immunolabel intracellularly for AGE-antibody 6D12 compared to the younger age group. The AGE-modified proteins, determined in the semimembranosus muscles from young (9 months) and old (27 months) F344 rats, identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry include creatine kinase, carbonic anhydrase III, beta-enolase, actin, and voltage-dependent anion-selective channel 1. Moreover, there is a significant increase in AGE modification of beta-enolase with age. These results identify a common subset of proteins that contain AGE and suggest that metabolic proteins are targets for glycation with aging.

http://www.ncbi.nlm....pubmed/18000139
 

[LeeYa]

But you don't need Fischer 344 Brown Norway F1 (F344BNF1) hybrid rats to show me that AGEs can accumulate in old age. Of course, that is what happens also in the human body.

 

The question is:

 

Are the AGEs already enriched in the youth in comparison to the childhood age?

(This is what the "accumulation of damage" theory postulates)

 

Or does the accumulation takes place later, when the body gradually shut down his reparation processes?

(This would be a prediction of the "progressive failure of existing repair mechanisms"-hypothesis)

[corb]

But you don't need Fischer 344 Brown Norway F1 (F344BNF1) hybrid rats to show me that AGEs can accumulate in old age. Of course, that is what happens also in the human body.

 

The question is:

 

Are the AGEs already enriched in the youth in comparison to the childhood age?

(This is what the "accumulation of damage" theory postulates)

 

Or does the accumulation takes place later, when the body gradually shut down his reparation processes?

(This would be a prediction of the "progressive failure of existing repair mechanisms"-hypothesis)

 

The paper I posted shows accumulation in any age group.

But you seem to have an aversion to actually reading what's being posted.

[xEva]

Thank you LeeYa for spelling it out, though I thought I did everything I could to convey the idea in the simplest terms possible.


So, niner, for the last time:
 

I don't see how an experiment may prove or disprove my observation of a simple, plainly seen fact that we don't age --i.e. don't accumulate damage-- while we're young. This is so obvious that it even sounds like an oxymoron.

And I am still to see a study that shows "damage accumulation" (beyond transient side-effects of an illness) in a young cohort. Not to go too far, the study linked by corb just above compares people under 30 with those over 60 and confirms that regenerative capacity is impaired in old age (>60). But where is the study that shows that a similar decline takes place in young groups, say, 20-25 compared to 25-30? This is what's claimed by the accumulating damage theory. Based on what?

So you're still trying to see molecular damage using only your eyes? Good luck with that. I posted a paper that had people as young as 16, but you weren't impressed with it. Photodamage on facial skin has been detected in pre-schoolers, but I'm not really feeling like digging up the reference, since you seem to have made up your mind.

You posted a paper that compared 16-yo to 90-yo. And corb posted a paper that compared 30-yo to 60. Such papers only confirm what can be accurately assessed at a first fleeting glance. Again: where are the papers that find accumulation of damage in a young cohort?

Edited by xEva, 20 January 2015 - 08:09 PM.

[xEva]

While there is a lot of trueth in your theory, don't underestimate the other theories. They are correct too. For example the wear ant tear theory: your teeth are being weared off each time you eat. The teeth of the very old people (in the cases when they have teeth) are weared off. My grand mother has two metal crowns, placed more than 30 years ago, and the metal is weared off (filed away) to such an extend, that the metal teeth has lost their form, and look like a flat surface,

Teeth can and do remineralize -- in a young organism that is. Since humans are subjects to odd diets, dentist and dental hygiene, a good example is a cat. And so, 5 years ago we took in a starving, young (about a year old) stray cat. The tip of her right canine was broken off, about 3 mm, and it was brown at the broken end. Now, 5 years later, the tooth is white, sharp and smooth, though it is still ~1mm shorter than her left canine. As I remember, it became all white after about 6 months with us. Would the same happen in an older animal? I doubt it, but who knows.

And so, when you speak about your grandma, please consider at what age her teeth were capped, and if it was after 25, I don't see how this is relevant to the discussion.

Edited by xEva, 20 January 2015 - 08:16 PM.

[LeeYa]

 

But you don't need Fischer 344 Brown Norway F1 (F344BNF1) hybrid rats to show me that AGEs can accumulate in old age. Of course, that is what happens also in the human body.

 

The question is:

 

Are the AGEs already enriched in the youth in comparison to the childhood age?

(This is what the "accumulation of damage" theory postulates)

 

Or does the accumulation takes place later, when the body gradually shut down his reparation processes?

(This would be a prediction of the "progressive failure of existing repair mechanisms"-hypothesis)

 

The paper I posted shows accumulation in any age group.

But you seem to have an aversion to actually reading what's being posted.

 

 

Actually, my reading is just from another viewpoint than yours.

Please take a look at the "raw data":

 

8 mo     1.38 ± 0.34

33 mo   5.92 ± 1.8

36 mo   22.64 ± 5.2*

 

I would say, between 8 and 33 months there are no dramatic changes, compared to the very last months. The accumulation rate appears to accelerate dramatically. Where does this acceleration come from? Really from the amount of AGEs in the food? Or is it because there happens a progressive abandon of clearance mechanisms?

 

You say, it is accumulation in any age group.

 

Please keep in mind, that the choosen examination points are not optimal for answering our question, because 33 months is not a youthful age for a rat.
 

Edited by LeeYa, 20 January 2015 - 08:35 PM.

[corb]

Again: where are the papers that find accumulation of damage in a young cohort?

 

http://onlinelibrary...77160802248039/

 

An interesting article that shows that indeed AGE accumulation happens in children.

Also it shows that it's less pronounced in obsess children which makes an interesting case for early renal failure and diabetes in the obese - their repair mechanisms work on overdrive and fail earlier. Makes sense to me

 

Where does this acceleration come from?

 

Probably renal failure.
Not unusual for aged mammals.

 

 

Edited by corb, 20 January 2015 - 09:47 PM.

[LeeYa]

 

Where does this acceleration come from?

 

Probably renal failure.
Not unusual for aged mammals.

 

I agree on that point.

http://onlinelibrary...77160802248039/

 

An interesting article that shows that indeed AGE accumulation happens in children.

Also it shows that it's less pronounced in obsess children which makes an interesting case for early renal failure and diabetes in the obese - their repair mechanisms work on overdrive and fail earlier. Makes sense to me

 

 

There are always AGEs present in the human body (even in childhood) simply because of the serum glucose levels. But to demonstrate AGE accumulation, you need a longitudinal study design.

 

However, thank you for this interesting paper. Unfortunately I don't have full access :(

[xEva]

I second that, no full access, and the abstract does not say anything about accumulation of AGEs in that young group.

None of the papers posted here so far showed accumulation of whatever 'damage' that was measured in a young cohort. So for those who still do not understand, here it comes again: in the papers that have been linked here, the young groups 16+ and <30 were compared to groups well over 30. Such comparisons are irrelevant here because no one claims that damage does not accumulate in people over 25-35 -- only that it does not accumulate in people under 25.

Is this so difficult to understand? I'll show what I mean on an example of a paper linked by corb above, where 3 age groups were compared, <30, 30-60, and >60. I found it peculiar that the abstract only spoke about the under 30 and the over 60 groups, omitting the middle group of 30-60. The abstract did say that, compared to the under-30 group, the over-60 group accumulated more.. ..whatever they measured. This sort of comparison is irrelevant for this discussion. And why did not they mention the 30-60 group? I did not see the full text, but let me guess: 'cause the data that compared 30-60 group with others were not statistically significant?

Another irrelevant paper on which niner still insists (-?!) took a huge cohort spanning 16-90 and showed a correlation of damage with age. Funny that when I brought this up, for the nth time in this thread alone (and it stared in another), 2 people clicked on "disagree" button, which shows that at least 2 people here have hard time comprehending reading material. If this post does not help them, they should not stress themselves coming back to this thread.

And I was also surprised to see that some moron clicked on "need references" button on my post about my cat. This is my direct experience, which I share here on the forum, the real value of which is, first of all, in sharing such personal experiences and observations, and, only secondly, discussing whatever. ..and, Mr moron, why didn't you clicked on the same button when seivtcho brought up his grandma?

In any rate, I see this discussion is deteriorating rapidly. There were 5 ad hominems in this thread already. This does not bode well for the accumulation of damage theory proponents.

But I am infinitely patient. I'll spell it for the last time:

Show accumulation of damage in a young cohort -- as opposed to simply presence, like in the latest paper linked by corb. I sincerely hope you understand the difference, and if you don't please don't post here. It's getting tiring.

Edited by xEva, 21 January 2015 - 12:03 AM.

[niner]

-According to glycation: If there would be no endogenous mechanims to get rid of it, how do you think that it is possible to lower HbA1c with Metformin in people with diabetis mellitus? Furthermore, there are tons of ingested AGEs every day. Lysosomes must be overloaded even bevor you reach school age, right?
Recently, there are even counterintuitive findings that indicate a benefit from AGEs: http://www.sciencedi...53155651400360X
(eventually a hormetic reaction, in terms of a reactivation of repair mechanisms?)
 
-Senescent zombie cells should be removed by apoptosis or by digestion from macrophages, if endogenous repair mechanisms return to work.

The reason that we can reduce HbA1c with metformin is because red blood cells have a relatively short lifetime, so they are constantly being turned over. That's our AGE repair mechanism, and it works ok in short-lived tissues. The problem is the long lived tissues like ECM and neurons.

Dietary AGEs are a problem, and have negative effects on health. Helen Vlassara has done seminal work in this area. It's possible to reduce them by choosing lower-AGE foods.

Lysosomes are unlikely to be overloaded in the very young. That problem seems to take decades to fully develop.

That's an interesting paper on the upside of AGEs, but those benefits are fairly obscure, and are still overshadowed by the damage done by AGEs.

It would be nice if senescent cells were removed properly. Most of them are, but some are defective in some way that prevents them from removing themselves cleanly via apoptosis. For those cells, it's not clear that the body has a good solution. Fortunately, we have essentially all the basic technology we need to remove them, although designing and proving therapies will probably take a couple decades. This is likely to be the first widely available damage repair technology.

[niner]

Another irrelevant paper on which niner still insists (-?!) took a huge cohort spanning 16-90 and showed a correlation of damage with age. Funny that when I brought this up, for the nth time in this thread alone (and it stared in another), 2 people clicked on "disagree" button, which shows that at least 2 people here have hard time comprehending reading material. If this post does not help them, they should not stress themselves coming back to this thread.

And I was also surprised to see that some moron clicked on "need references" button on my post about my cat. This is my direct experience, which I share here on the forum, the real value of which is, first of all, in sharing such personal experiences and observations, and, only secondly, discussing whatever. ..and, Mr moron, why didn't you clicked on the same button when seivtcho brought up his grandma?

In any rate, I see this discussion is deteriorating rapidly. There were 5 ad hominems in this thread already. This does not bode well for the accumulation of damage theory proponents.

But I am infinitely patient. I'll spell it for the last time:

Show accumulation of damage in a young cohort -- as opposed to simply presence, like in the latest paper linked by corb. I sincerely hope you understand the difference, and if you don't please don't post here. It's getting tiring.

 

The paper that I posted with a range of subjects from 16 to 90 showed a correlation with r = 0.92!  That means there was a near-linear relationship between the damage they were considering and the age of the subject.  How in God's name is that irrelevant?  It is exactly what you are asking for.  Here, I'll try again, this time with a different source, "Tendon and Ligament Biochemistry and Pathology", by Graham Riley.   (it's on sci-hub)  It has a graphical representation which should be easier to understand without requiring any knowledge of statistics  This is a graph of pentosidine (one of the AGE crosslinks) versus age of subject, looking at the biceps tendon. 

 

 Pentosidine vs age.PNG   11.32KB   2 downloads

 

 

Fig. 1.1.8 Pentosidine accumulation in human tendon. Pentosidine content was
measured by reversed-phase high-performance liquid chromatography (HPLC)
and expressed relative to the collagen content. (a) Pentosidine accumulated in
a linear fashion with age in a sample of biceps brachii tendons, demonstrating
minimal collagen turnover over lifetime.

 

You can see that the crosslink content of this long-lived tissue increases continuously from a very early age.

[xEva]

The paper that I posted with a range of subjects from 16 to 90 showed a correlation with r = 0.92!  That means there was a near-linear relationship between the damage they were considering and the age of the subject.  How in God's name is that irrelevant?  It is exactly what you are asking for.  Here, I'll try again, this time with a different source, "Tendon and Ligament Biochemistry and Pathology", by Graham Riley.   (it's on sci-hub)  It has a graphical representation which should be easier to understand without requiring any knowledge of statistics  This is a graph of pentosidine (one of the AGE crosslinks) versus age of subject, looking at the biceps tendon. 
 
Pentosidine vs age.PNG
 

Fig. 1.1.8 Pentosidine accumulation in human tendon. Pentosidine content was
measured by reversed-phase high-performance liquid chromatography (HPLC)
and expressed relative to the collagen content. (a) Pentosidine accumulated in
a linear fashion with age in a sample of biceps brachii tendons, demonstrating
minimal collagen turnover over lifetime.

 
You can see that the crosslink content of this long-lived tissue increases continuously from a very early age.

I really don't know what else to say. You keep bringing up that paper with cohort 16-92, or, this one, 10-85, while I explicitly asked above to please don't do that. I already posted in the other thread that the inclusion of 16-25 group in 26-92 group only strengthens the signal for the 26-92 group. It proves NOTHING for the 16-25 group.

For this tendon paper you posted, the same thing applies. I could not see the text and it's hard to judge from those blobs on the graph, how many people under 25 they actually had. It looks like maybe 3 to 5. Below is the same data for the group that is relevant to this discussion. Cross your heart and please tell me, is the result you see statistically significant?

PLEASE don't do that again.

Attached Files

•  penta25.png   8.5KB   1 downloads

[xEva]

Based on this hypothesis of systemic rejuvenation from young plasma, what would you expect from injecting plasma from young mice to old mice?
 
Aged Mice Repeatedly Injected with Plasma from Young Mice: A Survival Study
http://www.ncbi.nlm....les/PMC4215333/

I am a bit perplexed about this study. They housed both, plasma and control, groups in the same cages. They injected plasma group with the centrifuged blood pooled from young mice. Presumably, they also used one saline syringe to inject the control group. And now this:

Injections were done in parallel for control and experimental animals by a single operator at the same time of the day.

Throughout the experiment, investigators carrying out procedures and making observations were blinded with regard to whether animals belonged to the treatment or control group.

I wonder how the operator/investigators knew which mouse to inject with which syringe, if they were 'blinded' and all mice were housed in the same cages? What, they labeled each mouse and someone prepared a personal syringe for each? Not a word about this in the methods section.

As for their results, they did not find any improvement in lifespan, only a statistically insignificant shortening. They injected plasma weekly, once IV and once intraperitoneally, for the total 80-100% of "blood plasma volume of the whole organism" per month.

This suggests that the human trial that plans to infuse a pint (-?) weekly is unlikely to do anything useful for the recipients either. But we will wait for the results

[Kalliste]

That trial will almost certainly fail. I wonder if that will cause a loss of optimism for human parabiosis.

[LeeYa]

The reason that we can reduce HbA1c with metformin is because red blood cells have a relatively short lifetime, so they are constantly being turned over. That's our AGE repair mechanism, and it works ok in short-lived tissues. The problem is the long lived tissues like ECM and neurons.

 

 

I agree. As long as the tissues underwent a turnover and repair mechanisms are turned on, AGEs don't really matter. Fortunately, there is only a tiny fraction of "non-turnover" tissue. Even the extracellular matrix in the CNS should underwent a slow turnover due to microglia. The damage accumulation-theory should work in the lenses, however, because this compartment is not reached by repair mechanisms. But lenses are proposed to be one of the first tissues that can be cultured in a petri dish. This is not a life threatening issue.

 

Dietary AGEs are a problem, and have negative effects on health. Helen Vlassara has done seminal work in this area. It's possible to reduce them by choosing lower-AGE foods.

Lysosomes are unlikely to be overloaded in the very young. That problem seems to take decades to fully develop.

 

There is agreement, that dietary AGEs should be avoided.  After all, there is actually no avaliable method to restore endogenous repair mechanisms to the fullest extend.

 

It would be nice if senescent cells were removed properly. Most of them are, but some are defective in some way that prevents them from removing themselves cleanly via apoptosis. For those cells, it's not clear that the body has a good solution. Fortunately, we have essentially all the basic technology we need to remove them, although designing and proving therapies will probably take a couple decades. This is likely to be the first widely available damage repair technology.

 

 

In my eyes, the accumulation of senecent cells is a strong indicator of a dysrupted repair capacity.

I agree that removement technologies should work to extend lifespan, but restauration of endogenous repair mechanisms would be the smarter approach.

 

It is important to notice that the repair mechanisms don't work with full commitment for us. They could do better, if they are forced to. The whole phenomenon of hormesis is solely based on (a moderate) reactivation of repair. The same is also true for the benefit of physical excercise...

Edited by LeeYa, 21 January 2015 - 10:59 AM.

[corb]

It is important to notice that the repair mechanisms don't work with full commitment for us. They could do better, if they are forced to.

 

So I guess you're a fan of this theory?

http://www.sciencedi...531556514000874

 

It's actually not a bad theory - it combines damage and program and in fact gives a logical explanation why people start aging faster after a certain point.

It cites around a hundred papers. I'd say they've combined old aging theories with the new ones and made something that makes sense.

 

I don't dislike it. It plays well with SENS. Gives a solid explanation why "youthful" factors don't do anything for maximal lifespans. Gives a solid explanation why CR works.

Of course I'd like to point out, according to the paper the repair mechanisms don't work with full commitment because it has been profitable for our survival not only as a species but also as units. But it fits well with your views apart from that.

[addx]

A while ago opened a thread suggesting that this 'progressive failure' is more of a 'programmed progressive failure' and that ageing is a purposeful mechanism crafted by evolution - manifested exactly as described - by ceasing of repairs. Ceasing of body repairs after maturity increases selection pressure for "smart behavior" that avoids extra body stress. So behavior/nervous system is pressured to evolve smarter behavior tactics. As an organism matures it is infact ready to "take on life". After it starts "taking on life" there's no more (extensive) repairs or such repairs would inherently hide the behavioral lack of fitness which would reduce proper selection.

http://www.longecity...volution/page-1

The point of the thread was pretty much the same. To identify ageing as a purposeful mechanism which should enable us better to find threads of it in the human anatomy. Currently as ageing is considered a sum of random evolutionary failures across the body, there's little coherence in finding the root of it.

Edited by addx, 21 January 2015 - 03:50 PM.

[HighDesertWizard]

A while ago opened a thread suggesting that this 'progressive failure' is more of a 'programmed progressive failure' and that ageing is a purposeful mechanism crafted by evolution - manifested exactly as described - by ceasing of repairs. Ceasing of body repairs after maturity increases selection pressure for "smart behavior" that avoids extra body stress. So behavior/nervous system is pressured to evolve smarter behavior tactics. As an organism matures it is infact ready to "take on life". After it starts "taking on life" there's no more (extensive) repairs or such repairs would inherently hide the behavioral lack of fitness which would reduce proper selection.

http://www.longecity...volution/page-1

The point of the thread was pretty much the same. To identify ageing as a purposeful mechanism which should enable us better to find threads of it in the human anatomy. Currently as ageing is considered a sum of random evolutionary failures across the body, there's little coherence in finding the root of it.

 

The idea that better Explanations of Aging can help focus attention on specific mechanisms in the human anatomy is one I like...

 

Still, Aging Explanations, to be taken seriously, need to reference Evidence Nodes (aka, "Threads" in the quotation above) we now know are important. For example, we now know that NF-kB plays a critical role in morbidity and mortality and in many Aging Theories. We now know, in a way we didn't even 5 to 10 years ago, that Epigenetic factors play a role in every major health disorder and in the physical decline of aging. Let's add ROS, Telomeres, and a handful of other things to the list of Threads in the Human Anatomy we already know are important.

 

We know a great deal about the Threads our Explanations must be related to. To imagine that our Explanations don't have to address these and other Already Known "Threads" is a significant step in the wrong direction.

Edited by HighDesertWizard, 24 January 2015 - 11:56 PM.

[niner]

I really don't know what else to say. You keep bringing up that paper with cohort 16-92, or, this one, 10-85, while I explicitly asked above to please don't do that. I already posted in the other thread that the inclusion of 16-25 group in 26-92 group only strengthens the signal for the 26-92 group. It proves NOTHING for the 16-25 group.

For this tendon paper you posted, the same thing applies. I could not see the text and it's hard to judge from those blobs on the graph, how many people under 25 they actually had. It looks like maybe 3 to 5. Below is the same data for the group that is relevant to this discussion. Cross your heart and please tell me, is the result you see statistically significant?

PLEASE don't do that again.

 

 

Wow xEva, you are something else.    You added so much compression noise to the part of the graph you snipped out that it is illegible.  Here it is with less distortion, and including the point at about 27 years that you conveniently excised. 

 

 Pentosidine vs age young.GIF   6.45KB   2 downloads

Yes.  I believe this is statistically significant.  It shows EXACTLY what we would expect for AGE accumulation occurring continuously.  The teenagers have more than the children, and the ~27 year old has more than the teens.  Sorry, but 27 is not far enough from 25 to be "irrelevant", no matter how much you say it.   If biological chemistry worked the way you think it does, then you would not see a linear increase.  You would see a flat line that suddenly starts to rise in the mid twenties.  That's not what the data shows.    The rate of increase from teens to mid 20's is completely consistent with the rate seen in the older subjects.

 

If biochem works the way you think it does, and AGEs in people under 25 are getting removed, by what process is this occurring?  The only way I know of to get rid of them is to digest the protein and express a new one.  Do you think that children are constantly remodeling their ECM or their other long-lived tissues?  I don't think there is any evidence to that effect.

 

This hypothesis of yours appears to be based entirely on your visual impression of young adults, and not much else.  Have you ever spent much time around children?  If you have, perhaps you have noticed that their skin is very soft and smooth when they are very young, but it coarsens over time.  A two year old and a twelve year old have different skin, and a 22 year old continues the trend.

[Danail Bulgaria]

....

 

... It shows EXACTLY what we would expect for AGE accumulation occurring continuously.  ....

 

....

 

 

This may prove, actually, that an aging change accumulates with time, but does not disprove, that the repair mechanisms fail down with the age.
 

[niner]

 

... It shows EXACTLY what we would expect for AGE accumulation occurring continuously.  ....

 

This may prove, actually, that an aging change accumulates with time, but does not disprove, that the repair mechanisms fail down with the age.

 

The linear relationship between AGE content and chronological age suggests that there is no slowing.  The repair mechanisms that exist, essentially a destroy/rebuild process, are inadequate.  If we could speed up the destruction/rebuilding process, that could in theory change the slope of the curve, but if those processes are not exactly matched, all hell breaks loose.  Current efforts are aimed at developing methods to remove the AGEs without wrecking the protein.

[Danail Bulgaria]

Things are complex and regeneration of the human body exists. Each time a wound healed or a broken bone recovered in the human body it is a regeneration - adequate enough to recover the function of the damaged part. And in old people wounds and bones regenerate slower, so.. recovery processes actually falls down with the age. The bad thing is that the most diferentiated cells don't recover,

[LeeYa]

Two questions:

 

1) The germline seems to repair its damage, such as AGEs and mitochondrial mutations (with subsequent functional limitations) over millions of years. How does it happen?

 

2) In species with negligible senescence, repair mechanisms seem to be fully adequate?

 

 

 

Edited by LeeYa, 25 January 2015 - 05:12 PM.

[Danail Bulgaria]

1) I don't know

 

2) Yes. There is no other mechanism at which an organism to be immortal - it has constantly to repair its structures.