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Aging as progressive failure of existing repair mechanisms

aging theory repair mechanisms

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#31 HighDesertWizard

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Posted 03 January 2015 - 05:22 PM

AFAIK, the best case against the Accumulated Damage way of thinking about aging has been made by Harold Katcher in...
 
Studies that shed new light on aging

 

From the paper (on page 3) related to the discussion above...

 

The study of Stuart Chambers, (Chambers et al. 2007) show that there are marked age-dependent, order of magnitude differences in the transcriptional rates of many genes, and of these age-regulated genes, the regulation must be seen as anti-homeostatic. An example of this is the downregulation of DNA repair genes in mice, (Chambers 2007) at ages at which DNA defects show increased frequency and DNA repair becomes inefficient (Gorbunova 2007). Other examples will be considered later. One would certainly suspect that down-regulating the transcription rates of repair enzymes at or just prior to the time of increased DNA damage accumulation and the documented decreased ability for DNA repair ("inefficient repair" - () must have a causal connection.

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#32 sensei

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Posted 04 January 2015 - 12:09 AM

Do HeLa cervical cells http://en.wikipedia.org/wiki/HeLa still have their repair mechanisms functioning after all these years?  The cell line is 64 years old now.


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#33 seivtcho

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Posted 04 January 2015 - 01:55 PM

Good point. Cancer cells are immortal. How is this possible, if they accumulate damage? If they don't, then why? If they accumulate, then how they fix it so effectively?



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#34 niner

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Posted 04 January 2015 - 03:42 PM

 

AFAIK, the best case against the Accumulated Damage way of thinking about aging has been made by Harold Katcher in...
 
Studies that shed new light on aging

 

From the paper (on page 3) related to the discussion above...

 

The study of Stuart Chambers, (Chambers et al. 2007) show that there are marked age-dependent, order of magnitude differences in the transcriptional rates of many genes, and of these age-regulated genes, the regulation must be seen as anti-homeostatic. An example of this is the downregulation of DNA repair genes in mice, (Chambers 2007) at ages at which DNA defects show increased frequency and DNA repair becomes inefficient (Gorbunova 2007). Other examples will be considered later. One would certainly suspect that down-regulating the transcription rates of repair enzymes at or just prior to the time of increased DNA damage accumulation and the documented decreased ability for DNA repair ("inefficient repair" - () must have a causal connection.

 

That's an interesting paper.  Yet, I have a sense that Katcher wants aging to be programmed, and is not looking at all the evidence in a completely unbiased way.  Even in his choice of language in this quote, for example, he says "must" have a causal connection.   I would have said "might".    My two big questions are the following: First, why would evolution develop an aging program when most animals died, due to predation or infection, before they even had a chance to substantially age?  Second, what is the nature of the "program"?  How do we know that the effects he holds up as evidence of a program aren't simply responses to damage?



#35 niner

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Posted 04 January 2015 - 03:50 PM

Do HeLa cervical cells http://en.wikipedia.org/wiki/HeLa still have their repair mechanisms functioning after all these years?  The cell line is 64 years old now.

 

 

Good point. Cancer cells are immortal. How is this possible, if they accumulate damage? If they don't, then why? If they accumulate, then how they fix it so effectively?

 

 

HeLa cells have telomerase running full-tilt all the time.  That is one of the ways that cancer cells appear immortal.  Another is that they have typically lost the normal checks that detect damage and commit cellular suicide.  It's not that they aren't accumulating damage, it's that they aren't dying.  One way we know they accumulate damage is that tumors acquire a vast spectrum of mutations that you wouldn't find in normal tissue.  They also alter their energy metabolism in ways that slow the accumulation of damage.  Perhaps most important in this entire discussion, a point which Katcher doesn't address, is that aging isn't primarily a cellular problem; it's an organismic problem.  Many if not most forms of aging damage are extracellular in nature.


Edited by niner, 04 January 2015 - 03:51 PM.


#36 Avatar of Horus

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Posted 04 January 2015 - 04:27 PM

AFAIK, the best case against the Accumulated Damage way of thinking about aging has been made by Harold Katcher in...
 
Studies that shed new light on aging

 
From the paper (on page 3) related to the discussion above...
 
The study of Stuart Chambers, (Chambers et al. 2007) show that there are marked age-dependent, order of magnitude differences in the transcriptional rates of many genes, and of these age-regulated genes, the regulation must be seen as anti-homeostatic. An example of this is the downregulation of DNA repair genes in mice, (Chambers 2007) at ages at which DNA defects show increased frequency and DNA repair becomes inefficient (Gorbunova 2007). Other examples will be considered later. One would certainly suspect that down-regulating the transcription rates of repair enzymes at or just prior to the time of increased DNA damage accumulation and the documented decreased ability for DNA repair ("inefficient repair" - () must have a causal connection.

 
That's an interesting paper.  Yet, I have a sense that Katcher wants aging to be programmed, ...


Interestingly I have had sometimes this feeling (the "want") from the writings of proponents of the damage theories of aging. However I could never fully understand (or accept) the fuss (and the attacks) of either side about this, because (see below).
 

... Second, what is the nature of the "program"?  How do we know that the effects he holds up as evidence of a program aren't simply responses to damage?


To this last question:
I think that the answer (to this and also more generally) is that: you don't know. Instead: you have some data from which you create a hypothesis/theory, "a proposed explanation for a phenomenon", then you design an experiment to test it.
Just like he did and suggests: he collected studies, formed a hypothesis from them and (from the Abstract):

I will then briefly discuss models of aging and propose an experiment that would distinguish between those models and provide a basis for organismic rejuvenation.
...
A simple experiment is proposed to distinguish aging theories.



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#37 HighDesertWizard

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Posted 04 January 2015 - 06:51 PM

 

 

AFAIK, the best case against the Accumulated Damage way of thinking about aging has been made by Harold Katcher in...
 
Studies that shed new light on aging

 

From the paper (on page 3) related to the discussion above...

 

The study of Stuart Chambers, (Chambers et al. 2007) show that there are marked age-dependent, order of magnitude differences in the transcriptional rates of many genes, and of these age-regulated genes, the regulation must be seen as anti-homeostatic. An example of this is the downregulation of DNA repair genes in mice, (Chambers 2007) at ages at which DNA defects show increased frequency and DNA repair becomes inefficient (Gorbunova 2007). Other examples will be considered later. One would certainly suspect that down-regulating the transcription rates of repair enzymes at or just prior to the time of increased DNA damage accumulation and the documented decreased ability for DNA repair ("inefficient repair" - () must have a causal connection.

 

That's an interesting paper.  Yet, I have a sense that Katcher wants aging to be programmed, and is not looking at all the evidence in a completely unbiased way.  Even in his choice of language in this quote, for example, he says "must" have a causal connection.   I would have said "might".    My two big questions are the following: First, why would evolution develop an aging program when most animals died, due to predation or infection, before they even had a chance to substantially age?  Second, what is the nature of the "program"?  How do we know that the effects he holds up as evidence of a program aren't simply responses to damage?

 

 

niner... I appreciate your response...

 

I don't see the point of speculating about desire and motive. If Katcher is looking at the evidence in a biased way, then the thing to do is name the specific evidence he doesn't take into account or dismisses without justification.

 

Katcher says this about his view of what the Program is about...

As we will show, evidence points to aging being a programmed process controlled, in mammals, through factors present in their blood. The ultimate control of the process is epigenetic, but is coordinated across the body by soluble factors and juxtacrine interactions. I believe the process is a continuation of the developmental program, with a beginning and an end. 
 

Here is Katcher (from page 4) explaining why he thinks he knows that damage is the effect and not the cause.

Let us now debunk this paradigm of “wear and tear” for biological aging, using experimental evidence.
If aging results from the accumulation of damage or of toxic metabolic byproducts, then chronologically old cells should be damaged beyond the cell’s ability to repair itself. This is not the case, however based on clear results from decades of experimentation. Aging at the cellular, tissue, organ and organismic levels have been reversed by exposing the tissues of old animals to a young environment (Conboy, M 2009).
If cells can be rejuvenated by intrinsic means as a result of extrinsic signaling then the presumption that they are damaged beyond their ability to repair themselves is logically false. Thus, all theories of aging based on the “wear and tear” paradigm are proven wrong by experimentation. If a cell can be rejuvenated, it cannot be damaged beyond repair by aging.


#38 HighDesertWizard

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Posted 04 January 2015 - 06:57 PM

Josh Mitteldorf has usefully taken Katcher's paper further with discussion of what aged human blood has too much of or not enough of in How Young Blood Differs from Old...

 

Blood factors that we have too little of as we get older

  • melatonin, from pineal gland, controls daily cycle of sleep and waking
  • DHEA = dehydroepiandrosterone is a precursor of sex hormones and steroids
  • ubiquinone = CoQ10 is an anti-oxidant and electron transporter, used in mitochondria for energy production
  • thyroxine, produced in the thyroid, regulates many other hormones, stimulates activity
  • HSP70, heat shock protein, protects against muscle loss with age
  • progesterone, involved in menstruation, sleep cycle, mood; downregulates growth, increases insulin sensitivity
  • (HGH = human growth hormone)
  • (testosterone) primary male sex hormone
  • (estrogen) several primary female sex hormones

Blood factors that we have too much of as we get older

  • Wnt, a growth promoter associated with cancer
  • NFkB, a cytokine which triggers inflammation
  • LH (luteinizing hormone) & FSH (follicle-stimulating hormone), associated with ovulation in women and sperm production in men.  Increase late in life for both men and women.
  • Estradiol, a female sex hormone
  • CCL11 (a growth-inhibiting chemokine, see Villeda’s work above)

Edited by HighDesertWizard, 04 January 2015 - 06:58 PM.


#39 corb

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Posted 04 January 2015 - 07:05 PM

I'd say my biggest problem with Katcher's paper is he's casually shooting down any and every known probable cause - telomeres, mitochondria, metabolism, thymus gland shrinking, any other external cause, so on, not just wear and tear - he's not exactly laying down a new theory, he's just critiquing the already laid down ones.

 

We have to consider something when epigenetic and genetic theories are concerned - not every tissue in the body is capable of regeneration after a certain point of development, so even though a causation of it's aging might lay in a pre-programmed mechanism, any intervention that would be safe to use might actually be what has already been proposed by "wear and tear" proponents.

 

Also and by far not the least of importance though in vitro experiments aren't the perfect proof of concept when it comes to biology. A live organism has many more random events happening in it's system than a cell culture in a petrie dish.

 

I still think supplementing "young" factors in plasma is a cheap, easy, first generation life extension tech though, don't get me wrong. It's been shown to work to a degree and it's about as safe as any medical intervention.


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#40 ceridwen

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Posted 04 January 2015 - 07:21 PM

Do you know where one can get youthful plasma?

#41 Avatar of Horus

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Posted 04 January 2015 - 09:02 PM

I think this "youth factors" thing may be a good direction for future research, e.g. for the possible controlled aspects of the aging process, including the regulation of the "existing repair mechanisms"; we need much more data though, as this is in its infancy yet.
Here is its topic BTW:
Young Blood Reverses Signs of Aging in Old Mice
http://www.longecity...ng-in-old-mice/



#42 seivtcho

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Posted 04 January 2015 - 10:23 PM

 

HeLa cells have telomerase running full-tilt all the time.  That is one of the ways that cancer cells appear immortal.  Another is that they have typically lost the normal checks that detect damage and commit cellular suicide.  It's not that they aren't accumulating damage, it's that they aren't dying.  One way we know they accumulate damage is that tumors acquire a vast spectrum of mutations that you wouldn't find in normal tissue.  They also alter their energy metabolism in ways that slow the accumulation of damage.  Perhaps most important in this entire discussion, a point which Katcher doesn't address, is that aging isn't primarily a cellular problem; it's an organismic problem.  Many if not most forms of aging damage are extracellular in nature.

 

 

Alright, but aren't the genes, that code the telomerase getting damage accumulation too? If enough damage accumulates on the telomerase gene, they will produce an unefficient telomerase, and the telomerase will stop working. How is it happening, that the telomerase gene dos not accumulate damage? Plus even if the self - destruction mechanism does not exist anymore, if enough damage is accumulated, the cell simply will die from a stop of its entire metabolism (since all the enzymes will eventually become wrong and non effective). So, the question for the damage accumulation solving in the cancer cells is still valid, according to me.



#43 corb

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Posted 05 January 2015 - 03:34 AM

 

 

HeLa cells have telomerase running full-tilt all the time.  That is one of the ways that cancer cells appear immortal.  Another is that they have typically lost the normal checks that detect damage and commit cellular suicide.  It's not that they aren't accumulating damage, it's that they aren't dying.  One way we know they accumulate damage is that tumors acquire a vast spectrum of mutations that you wouldn't find in normal tissue.  They also alter their energy metabolism in ways that slow the accumulation of damage.  Perhaps most important in this entire discussion, a point which Katcher doesn't address, is that aging isn't primarily a cellular problem; it's an organismic problem.  Many if not most forms of aging damage are extracellular in nature.

 

 

Alright, but aren't the genes, that code the telomerase getting damage accumulation too? If enough damage accumulates on the telomerase gene, they will produce an unefficient telomerase, and the telomerase will stop working. How is it happening, that the telomerase gene dos not accumulate damage? Plus even if the self - destruction mechanism does not exist anymore, if enough damage is accumulated, the cell simply will die from a stop of its entire metabolism (since all the enzymes will eventually become wrong and non effective). So, the question for the damage accumulation solving in the cancer cells is still valid, according to me.

 

As far as I know the telomerase component catalyzing genes have to already be mutated to some degree for a cell to become cancerous. So it is not a detriment.

Also as niner already pointed out cancer cells use alternative metabolic pathways - for instance they don't need (and most of them don't have a ready supply of) oxygen to operate - and as we know ROS is a major cause of damage in cells so it's possible they accumulate damage much much slower than normal cells by avoiding oxygen completely.


Edited by corb, 05 January 2015 - 03:37 AM.


#44 seivtcho

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Posted 05 January 2015 - 02:40 PM

Nothing runs forever if let by its own. It is logical if the telomerase component catalyzing genes mutate long enough, they to reach the point at which they are no longer telomerase component catalyzing genes, ant the cellular divisions will stop. This obviously is not happening. According to me they have to also repair periodically their genome.



#45 niner

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Posted 05 January 2015 - 10:12 PM

niner... I appreciate your response...

 

I don't see the point of speculating about desire and motive. If Katcher is looking at the evidence in a biased way, then the thing to do is name the specific evidence he doesn't take into account or dismisses without justification.

 

Katcher says this about his view of what the Program is about...

As we will show, evidence points to aging being a programmed process controlled, in mammals, through factors present in their blood. The ultimate control of the process is epigenetic, but is coordinated across the body by soluble factors and juxtacrine interactions. I believe the process is a continuation of the developmental program, with a beginning and an end. 
 

Here is Katcher (from page 4) explaining why he thinks he knows that damage is the effect and not the cause.

Let us now debunk this paradigm of “wear and tear” for biological aging, using experimental evidence.
If aging results from the accumulation of damage or of toxic metabolic byproducts, then chronologically old cells should be damaged beyond the cell’s ability to repair itself. This is not the case, however based on clear results from decades of experimentation. Aging at the cellular, tissue, organ and organismic levels have been reversed by exposing the tissues of old animals to a young environment (Conboy, M 2009).
If cells can be rejuvenated by intrinsic means as a result of extrinsic signaling then the presumption that they are damaged beyond their ability to repair themselves is logically false. Thus, all theories of aging based on the “wear and tear” paradigm are proven wrong by experimentation. If a cell can be rejuvenated, it cannot be damaged beyond repair by aging.

 

Katcher says "Thus, all theories of aging based on the “wear and tear” paradigm are proven wrong by experimentation. If a cell can be rejuvenated, it cannot be damaged beyond repair by aging."  Wait a minute.  "all theories" are "proven wrong"?  That's a pretty strong statement based on some relatively thin experimental results.  It's possible to rejuvenate an old cell by the application of various factors, but that's because the cell was still in a recoverable state.  If it were damaged enough, it would be dead or deeply senescent.  Katcher also doesn't have a word to say about one of the most obvious visual signs of aging, damage to the extracellular matrix from glycation and UV damage.  If he can revert that with paracrine factors, then my hat's off to him.  I don't think he can.  I don't think he can do anything to fix lysosomes that are clogged with indigestible junk, either.   Essentially he is looking at a small subset of the aging process, and making grandiose statements based on experiments that may or may not be relevant to normal human aging.

 

It may well turn out that some aspects of aging are "programmed", but I don't think that we can toss out all damage-related theories.  Perhaps, some decades from now, we will be getting periodic damage repair treatments as well as regular treatments to maintain a youthful signalling environment.



#46 Avatar of Horus

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Posted 06 January 2015 - 06:07 AM

... lysosomes ...
...
It may well turn out that some aspects of aging are "programmed", but I don't think that we can toss out all damage-related theories.  Perhaps, some decades from now, we will be getting periodic damage repair treatments as well as regular treatments to maintain a youthful signalling environment.

 
Regarding the lysosomes:
an older blog article discussing similar questions: about the relationship between some of the controlled and the damage-based aging-related changes, covering the discovery: http://www.abc.net.a.../11/2331197.htm, 11 August 2008:

...
The researchers, led by Associate Professor Ana Maria Cuervo, blocked the ageing process in mice livers by stopping the build-up of harmful proteins inside the organ's cells.

As people age their cells become less efficient at getting rid of damaged protein resulting in a build-up of toxic material that is especially pronounced in Alzheimer's, Parkinson's and other neurodegenerative disorders. ...

 
the blog article:
Lysosomal Activity Declines With Aging
https://www.fightagi...-with-aging.php
 
the first part discusses the damage-based approach, like the SENS, and the second part is about the above finding and their relationship:

...
The second process at work in the decline of lysosomal function was more recently established. Items to be recycled by lysosomes must be identified and steered to a lysosome, a process accomplished by cellular machinery that includes chaperone molecules and receptors on the lysosomes themselves. These lysosomal receptors decline with age, however, a change that may or may not result from the accumulation of biochemical junk discussed above.
 

Quote:
    The cells of all organisms have several surveillance systems designed to find, digest and recycle damaged proteins. ... One of these surveillance systems - responsible for handling 30 percent or more of damaged cellular protein - uses molecules known as chaperones to seek out damaged proteins. After finding such a protein, the chaperone ferries it towards one of the cell's many lysosomes ... Dr. Cuervo found that the chaperone surveillance system, in particular, becomes less efficient as cells become older, resulting in a buildup of undigested proteins within the cells. She also detected the primary cause for this age-related decline: a fall-off in the number of lysosomal receptors capable of binding chaperones and their damaged proteins.


Last year Cuervo demonstrated old mouse livers functioning as well as young mouse livers through genetic engineering of a breed that produced more lysosomal receptors. It remains to be seen whether this result holds for all tissues and organs, as well as what exactly is the root cause of age-related decline in receptors.

Lysosomal decline is typical of what researchers know of the causes of aging. ...


also two older Longecity topics about this:
Scientists REVERSE age-related functional decline in mouse livers!
http://www.longecity...n-mouse-livers/

Scientists stop the ageing process
http://www.longecity...ageing-process/

#47 Kalliste

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Posted 06 January 2015 - 10:20 AM

Josh Mitteldorf has an interesting blog where he sometimes gets on this subject. He is on the programmed aging side of things.

 

 

Most people misunderstand what aging is.  It’s not just the public who have been deceived — Most scientists and medical researchers who study aging are on the wrong track.

The culprit is the “natural medicine” movement that has dominated thinking about our bodies for the last 50 years.  “Respect the body’s wisdom.  Work with the body to fix what has gone wrong.”  This approach has worked so well with injuries and many diseases that it is understandable that people want to extend it to aging as well.

Diseases of aging have been treated as if they were something that goes wrong, something we have to help the body to fix.  But in fact, the evidence accumulating in recent decades is that aging is not something that goes wrong, and the body is not trying to fix it.  Aging is natural.  It is the body shutting itself down, putting itself out of the way after it has done its job, finished reproduction.

 

What is Aging? Most Scientists Still Get it Wrong

http://joshmitteldor...l-get-it-wrong/

 



#48 niner

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Posted 07 January 2015 - 12:22 AM

 

... lysosomes ...
...
It may well turn out that some aspects of aging are "programmed", but I don't think that we can toss out all damage-related theories.  Perhaps, some decades from now, we will be getting periodic damage repair treatments as well as regular treatments to maintain a youthful signalling environment.

 
Regarding the lysosomes:
an older blog article discussing similar questions: about the relationship between some of the controlled and the damage-based aging-related changes, covering the discovery: http://www.abc.net.a.../11/2331197.htm, 11 August 2008:

...The researchers, led by Associate Professor Ana Maria Cuervo, blocked the ageing process in mice livers by stopping the build-up of harmful proteins inside the organ's cells.
As people age their cells become less efficient at getting rid of damaged protein resulting in a build-up of toxic material that is especially pronounced in Alzheimer's, Parkinson's and other neurodegenerative disorders. ...

 
the blog article:
Lysosomal Activity Declines With Aging
https://www.fightagi...-with-aging.php
 
the first part discusses the damage-based approach, like the SENS, and the second part is about the above finding and their relationship:

..The second process at work in the decline of lysosomal function was more recently established. Items to be recycled by lysosomes must be identified and steered to a lysosome, a process accomplished by cellular machinery that includes chaperone molecules and receptors on the lysosomes themselves. These lysosomal receptors decline with age, however, a change that may or may not result from the accumulation of biochemical junk discussed above.
 

Quote:
    The cells of all organisms have several surveillance systems designed to find, digest and recycle damaged proteins. ... One of these surveillance systems - responsible for handling 30 percent or more of damaged cellular protein - uses molecules known as chaperones to seek out damaged proteins. After finding such a protein, the chaperone ferries it towards one of the cell's many lysosomes ... Dr. Cuervo found that the chaperone surveillance system, in particular, becomes less efficient as cells become older, resulting in a buildup of undigested proteins within the cells. She also detected the primary cause for this age-related decline: a fall-off in the number of lysosomal receptors capable of binding chaperones and their damaged proteins.


Last year Cuervo demonstrated old mouse livers functioning as well as young mouse livers through genetic engineering of a breed that produced more lysosomal receptors. It remains to be seen whether this result holds for all tissues and organs, as well as what exactly is the root cause of age-related decline in receptors.

 

This is a great example, discussing two different ways that lysosomes malfunction.  One of them, the accumulation of indigestible junk, is particularly a problem in long lived cells like neurons, and is central to the development of atherosclerosis.  The other process is due to a fall-off in lysosomal chaperone receptors.  I don't yet know exactly how this relates to human aging, but it's reasonable to assume that it's significant. 

 

I have two things to say about this:  First, the existence of the second failure mechanism doesn't mean that the first one, which is clearly a form of damage, is not important.  Secondly, as FightAging points out, we don't know why the lysosomal receptor activity drops off.  Perhaps it's the consequence of other forms of damage, or perhaps it's the erroneous playing out of a development program, but I don't think that there's a lick of evidence that it's occurring, as Mittledorf et al. might have it, because "it's the right thing", or that God wants it to be that way.



#49 niner

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Posted 07 January 2015 - 01:05 AM

Josh Mitteldorf has an interesting blog where he sometimes gets on this subject. He is on the programmed aging side of things.

 

Most people misunderstand what aging is.  It’s not just the public who have been deceived — Most scientists and medical researchers who study aging are on the wrong track.

The culprit is the “natural medicine” movement that has dominated thinking about our bodies for the last 50 years.  “Respect the body’s wisdom.  Work with the body to fix what has gone wrong.”  This approach has worked so well with injuries and many diseases that it is understandable that people want to extend it to aging as well.

Diseases of aging have been treated as if they were something that goes wrong, something we have to help the body to fix.  But in fact, the evidence accumulating in recent decades is that aging is not something that goes wrong, and the body is not trying to fix it.  Aging is natural.  It is the body shutting itself down, putting itself out of the way after it has done its job, finished reproduction.

 

What is Aging? Most Scientists Still Get it Wrong

http://joshmitteldor...l-get-it-wrong/

 

Wow.  How creepy.  Around here, Mitteldorf would be known as a "deathist".   Usually, when someone insists that everyone else has it wrong, that's a red flag...



#50 corb

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Posted 07 January 2015 - 03:20 AM

 

Josh Mitteldorf has an interesting blog where he sometimes gets on this subject. He is on the programmed aging side of things.

 

Most people misunderstand what aging is.  It’s not just the public who have been deceived — Most scientists and medical researchers who study aging are on the wrong track.

The culprit is the “natural medicine” movement that has dominated thinking about our bodies for the last 50 years.  “Respect the body’s wisdom.  Work with the body to fix what has gone wrong.”  This approach has worked so well with injuries and many diseases that it is understandable that people want to extend it to aging as well.

Diseases of aging have been treated as if they were something that goes wrong, something we have to help the body to fix.  But in fact, the evidence accumulating in recent decades is that aging is not something that goes wrong, and the body is not trying to fix it.  Aging is natural.  It is the body shutting itself down, putting itself out of the way after it has done its job, finished reproduction.

 

What is Aging? Most Scientists Still Get it Wrong

http://joshmitteldor...l-get-it-wrong/

 

Wow.  How creepy.  Around here, Mitteldorf would be known as a "deathist".   Usually, when someone insists that everyone else has it wrong, that's a red flag...

 

 

He is not a deathist per se. But he uses unfortunate wording and has some unfortunate ideas. And the most unfortunate part, the brass at Google's startup follow the same way of  thinking.



#51 Kalliste

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Posted 07 January 2015 - 05:52 AM

 

Josh Mitteldorf has an interesting blog where he sometimes gets on this subject. He is on the programmed aging side of things.

 

Most people misunderstand what aging is.  It’s not just the public who have been deceived — Most scientists and medical researchers who study aging are on the wrong track.

The culprit is the “natural medicine” movement that has dominated thinking about our bodies for the last 50 years.  “Respect the body’s wisdom.  Work with the body to fix what has gone wrong.”  This approach has worked so well with injuries and many diseases that it is understandable that people want to extend it to aging as well.

Diseases of aging have been treated as if they were something that goes wrong, something we have to help the body to fix.  But in fact, the evidence accumulating in recent decades is that aging is not something that goes wrong, and the body is not trying to fix it.  Aging is natural.  It is the body shutting itself down, putting itself out of the way after it has done its job, finished reproduction.

 

What is Aging? Most Scientists Still Get it Wrong

http://joshmitteldor...l-get-it-wrong/

 

Wow.  How creepy.  Around here, Mitteldorf would be known as a "deathist".   Usually, when someone insists that everyone else has it wrong, that's a red flag...

 

 

Creepy?? He is a bit too obsessed with supplements and he sometimes writes about completely different things than LE. I'm not qualified to assess all the claims he make. I can only hope we can test them by using repair-tech on living organisms soon. If he is right I guess he is implying that the SENS deal might not be good enough since some background death-program still wants you out.


Edited by Cosmicalstorm, 07 January 2015 - 05:53 AM.


#52 Avatar of Horus

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Posted 08 January 2015 - 01:19 PM

...

This is a great example, discussing two different ways that lysosomes malfunction. One of them, the accumulation of indigestible junk, is particularly a problem in long lived cells like neurons, and is central to the development of atherosclerosis. The other process is due to a fall-off in lysosomal chaperone receptors. I don't yet know exactly how this relates to human aging, but it's reasonable to assume that it's significant.

I have two things to say about this: First, the existence of the second failure mechanism doesn't mean that the first one, which is clearly a form of damage, is not important. Secondly, as FightAging points out, we don't know why the lysosomal receptor activity drops off. Perhaps it's the consequence of other forms of damage, or perhaps it's the erroneous playing out of a development program, but I don't think that there's a lick of evidence that it's occurring, as Mittledorf et al. might have it, because "it's the right thing", or that God wants it to be that way.


Yes, something like this, but if something is an endogenous process, like a gene expression regulation, then it belongs to the programmed aging features. And if true and factual this and the similar studies - you are right - don't prove (in themselves) that aging is programmed (fully), but disprove the "damage-only" views.
That's why I think that, based on the currently available data, the only acceptable scientific viewpoint is something similar to your sentence (that I quoted at the beginning of my previous post, this):
 

...
It may well turn out that some aspects of aging are "programmed", but I don't think that we can toss out all damage-related theories. ...


Edited by Avatar of Horus, 08 January 2015 - 01:20 PM.


#53 niner

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Posted 08 January 2015 - 03:24 PM

 

 

Josh Mitteldorf has an interesting blog where he sometimes gets on this subject. He is on the programmed aging side of things.

 

Most people misunderstand what aging is.  It’s not just the public who have been deceived — Most scientists and medical researchers who study aging are on the wrong track.

The culprit is the “natural medicine” movement that has dominated thinking about our bodies for the last 50 years.  “Respect the body’s wisdom.  Work with the body to fix what has gone wrong.”  This approach has worked so well with injuries and many diseases that it is understandable that people want to extend it to aging as well.

Diseases of aging have been treated as if they were something that goes wrong, something we have to help the body to fix.  But in fact, the evidence accumulating in recent decades is that aging is not something that goes wrong, and the body is not trying to fix it.  Aging is natural.  It is the body shutting itself down, putting itself out of the way after it has done its job, finished reproduction.

 

What is Aging? Most Scientists Still Get it Wrong

http://joshmitteldor...l-get-it-wrong/

 

Wow.  How creepy.  Around here, Mitteldorf would be known as a "deathist".   Usually, when someone insists that everyone else has it wrong, that's a red flag...

 

Creepy?? He is a bit too obsessed with supplements and he sometimes writes about completely different things than LE. I'm not qualified to assess all the claims he make. I can only hope we can test them by using repair-tech on living organisms soon. If he is right I guess he is implying that the SENS deal might not be good enough since some background death-program still wants you out.

 

I'm sure he's a fine guy and all, but I found this particular sentiment, that death is natural and good and we should just accept it and lay down and die because it's the right thing... to be creepy.  And isn't it pretty much the definition of deathist?  Further, blaming the supposed error that aging might be fixed on the "natural medicine" movement just seems bizarre.

 

If all he really means is "SENS might not be enough", then sure, I'm in complete agreement with that.  However, the programmed aging guys (I'm particularly thinking of Katcher here) take it a lot farther, and try to say that damage isn't important at all.  Mittledorf might think that SENS isn't enough, but it sounds like he thinks we shouldn't even try SENS, because death is natural and good.  We could take the massive amount of money that we're wasting on SENS and buy a few hundred caskets.


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#54 Kalliste

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Posted 08 January 2015 - 04:54 PM

God no Niner. I think you completely misunderstand him.

He is totally in with SENS and thinks that death should be avoided. He is perhaps a bit too excited by hormesis and supplements, but not too much imo.

But he does believe that evolution came up with aging as a way to speed up evolution or avoid population explosions and the resulting extinctions. At least I think this is it. I've been reading his blog for a year. Or am I misunderstanding you?



#55 Kevnzworld

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Posted 08 January 2015 - 05:17 PM

I've also followed Josh for awhile. I don't always agree with him, but his take is usually pretty informed.
I think he is saying something that we all know. Aging, without intervention is programmed and happens via biology and environment. Without intervention, Sens, supplements, repair or interruption we will die, mostly in our eighth decade.
I've witnessed so many people enter their 80's relatively healthy , yet few escape it and those that do have few years left.
Will any of the strategies the people on this forum currently employ do much if anything to change that? That's unknown.
I believe it will, that's why I do what I do...maybe because it makes me feel like I have some amount of control over the process. I may be delusional, but happier aging with that approach.

#56 corb

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Posted 08 January 2015 - 05:37 PM

God no Niner. I think you completely misunderstand him.

He is totally in with SENS and thinks that death should be avoided. He is perhaps a bit too excited by hormesis and supplements, but not too much imo.

But he does believe that evolution came up with aging as a way to speed up evolution or avoid population explosions and the resulting extinctions. At least I think this is it. I've been reading his blog for a year. Or am I misunderstanding you?

 

He's also into telomere lengthening and believes it's the prime target for intervention when it comes to aging. So definitely not a deathist. But he needs to work on his wording, his stances are kind of unclear sometimes.



#57 HighDesertWizard

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Posted 08 January 2015 - 08:51 PM

I'm sure he's a fine guy and all, but I found this particular sentiment, that death is natural and good and we should just accept it and lay down and die because it's the right thing... to be creepy. And isn't it pretty much the definition of deathist? Further, blaming the supposed error that aging might be fixed on the "natural medicine" movement just seems bizarre.

If all he really means is "SENS might not be enough", then sure, I'm in complete agreement with that. However, the programmed aging guys (I'm particularly thinking of Katcher here) take it a lot farther, and try to say that damage isn't important at all. Mittledorf might think that SENS isn't enough, but it sounds like he thinks we shouldn't even try SENS, because death is natural and good. We could take the massive amount of money that we're wasting on SENS and buy a few hundred caskets.

As others have noted above, there are a few statements in the two paragraphs above that are profound mischaracterizations of what is going on in Josh Mitteldorf's work.

Specifically, to suggest that Mitteldorf advocates that "we should just accept it [death] and lay down and die because it's the right thing" is outrageous.

In case anyone wonders, these are the kind of gross mischaracterizations by a prominent Longecity moderator that can trigger the feeling that the official dogma at Longecity is the SENS approach and anyone criticizing it might be attacked unfairly.

Edited by HighDesertWizard, 08 January 2015 - 09:14 PM.


#58 niner

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Posted 08 January 2015 - 09:19 PM

 

I'm sure he's a fine guy and all, but I found this particular sentiment, that death is natural and good and we should just accept it and lay down and die because it's the right thing... to be creepy. And isn't it pretty much the definition of deathist? Further, blaming the supposed error that aging might be fixed on the "natural medicine" movement just seems bizarre.

If all he really means is "SENS might not be enough", then sure, I'm in complete agreement with that. However, the programmed aging guys (I'm particularly thinking of Katcher here) take it a lot farther, and try to say that damage isn't important at all. Mittledorf might think that SENS isn't enough, but it sounds like he thinks we shouldn't even try SENS, because death is natural and good. We could take the massive amount of money that we're wasting on SENS and buy a few hundred caskets.

As others have noted above, there are a few statements in the two paragraphs above that are profound mischaracterizations of what is going on in Josh Mitteldorf's work.

Specifically, to suggest that Mitteldorf advocates that "we should just accept it [death] and lay down and die because it's the right thing" is outrageous.

In case anyone wonders, these are the kind of gross mischaracterizations by a prominent Longecity moderator that can trigger the feeling that the official dogma at Longecity is the SENS approach and anyone criticizing it will be attacked unfairly.

 

 

I don't follow Mitteldorf closely; I've read his blog a few times, and have found myself in general disagreement with what I've seen.  As I said in the post you quoted, I'm speaking of this particular sentiment that he expressed:
 

Diseases of aging have been treated as if they were something that goes wrong, something we have to help the body to fix.  But in fact, the evidence accumulating in recent decades is that aging is not something that goes wrong, and the body is not trying to fix it.  Aging is natural.  It is the body shutting itself down, putting itself out of the way after it has done its job, finished reproduction.



He's saying that aging isn't something going wrong-- in other words, it's "right". He says it's "natural", etc. etc. Did I really "mischaracterize" that passage? It sure as hell sounds like he thinks we should accept it, and that it's right and good.   I don't think I was being "outrageous".    Maybe I've missed the posts in which he's interested in doing something about aging, and he's not really a deathist, but like corb said, if that's the case then his choice of language here is horrible.

 

Finally, Longecity doesn't have an "official dogma".  I welcome all critiques of SENS that are evidence-based and sensible.  I will not give up my right to critique them in turn.  If you think any of those critiques are unfair, then tell us what's unfair about them.  I'm open to new ideas, if they are, again, evidence-based and sensible.


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#59 HighDesertWizard

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Posted 10 January 2015 - 10:55 PM

He's saying that aging isn't something going wrong-- in other words, it's "right". He says it's "natural", etc. etc. Did I really "mischaracterize" that passage? It sure as hell sounds like he thinks we should accept it, and that it's right and good.   I don't think I was being "outrageous".    Maybe I've missed the posts in which he's interested in doing something about aging, and he's not really a deathist, but like corb said, if that's the case then his choice of language here is horrible.

 

niner... I have much appreciated your remarks in many threads. You are great at insisting that we all have evidence to justify statements we make...

 

My posting links to Katcher and Mitteldorf were on topic in this thread. I posted the lists of blood/plasma factors that Mitteldorf blogged about that make it clear he's interested in doing something about aging.

 

Apparently, you ignored the significance of that post in this thread as you've continued to make statements about what his words "sound like" rather than spend a little time getting familiar with his actual work.

 

God no Niner. I think you completely misunderstand him.

 

I'm not the only person who objected to your statement about Mitteldorf. I'm not the only person in this thread who has expressed concern about the openness of those with a SENS orientation to new evidence (like the science of Epigenetic Rejuvenation) and the views of others about that evidence at Longecity.

 

Let's get back to detailed study and evidence discussion.


Edited by HighDesertWizard, 10 January 2015 - 11:06 PM.


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#60 niner

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Posted 11 January 2015 - 05:09 AM

 

He's saying that aging isn't something going wrong-- in other words, it's "right". He says it's "natural", etc. etc. Did I really "mischaracterize" that passage? It sure as hell sounds like he thinks we should accept it, and that it's right and good.   I don't think I was being "outrageous".    Maybe I've missed the posts in which he's interested in doing something about aging, and he's not really a deathist, but like corb said, if that's the case then his choice of language here is horrible.

 

niner... I have much appreciated your remarks in many threads. You are great at insisting that we all have evidence to justify statements we make...

 

My posting links to Katcher and Mitteldorf were on topic in this thread. I posted the lists of blood/plasma factors that Mitteldorf blogged about that make it clear he's interested in doing something about aging.

 

Apparently, you ignored the significance of that post in this thread as you've continued to make statements about what his words "sound like" rather than spend a little time getting familiar with his actual work.

 

God no Niner. I think you completely misunderstand him.

 

I'm not the only person who objected to your statement about Mitteldorf. I'm not the only person in this thread who has expressed concern about the openness of those with a SENS orientation to new evidence (like the science of Epigenetic Rejuvenation) and the views of others about that evidence at Longecity.

 

Let's get back to detailed study and evidence discussion.

 

HighDes, it sounds like I've offended you rather greviously.  Sorry.  I've talked about what I see as the flaws in the overall programmed aging scheme, but no one seems to be refuting those points.   I admitted that maybe he isn't a deathist, but again, as corb said, his choice of language in that one remark was horrible.  Words have consequences.  They're the currency we use here to exchange ideas-- People post words, other people respond to them.  Did that post really deserve an "ill informed" rating?  If so, why?  Maybe you should spend less time chiding me and more time convincing me that you and Katcher and Mitteldorf are right.    So maybe you could start by explaining why evolution went to the trouble of creating an aging program when animals were already dropping like flies (and drosophila were dropping like themselves) due to infection and predation.  What would be the mechanism for that?  I don't think group selection is enough.  How about presenting some of the great new evidence that you think I'm not open to?   Just because I call BS on a bad idea doesn't mean I'm not open to a good one.


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