266 replies to this topic

[niner]

If intermittent fasting changed this dynamic in any meaningful way, we would know it. As I wrote earlier, Muslims that fast annually during Ramadan do not live longer than non fasters.

 

Ramadan is a fairly light-duty form of IF.  It's more like having a "really late breakfast" for a month.  Or, to put it another way, instead of eating during the day, you eat at night.

[xEva]

@Kevnzworld:

Ramadan fast is not a continuous fast that lasts for days or weeks. Instead, it's a dry fast from sunup to sundown, with plenty of eating and drinking during the night. But the studies of monks, who did regular long fasts, showed them living well into their 90s in far better health and mental ability than their lay counterparts.


@niner:
 

Oh BS. Don't accuse me of "misrepresenting facts". There have been two studies posted with subjects as young as ten! You just don't accept published data if it doesn't agree with your erroneous hypothesis.

BS? The ONE AND ONLY relevant study that you posted, with a 10-yo, had the sample size of exactly 5. Please do not mention it again.
 

It was only unconvincing to you, because you refuse to be convinced. You have posted NO data supporting your contention that people under 25 have a unicorn-like ability to eliminate crosslinks in the ECM, an ability that is then lost.

That's right, I am not convinced by a study of 5.

And, according to the current state of knowledge, AGEs in ECM are broken down by proteolysis and released into the circulation to be filtered out by kidneys. You say that this only happens in tissues with a higher turnover rate. But what if some tissues are not meant to be turned over frequently and the reason is that some of the crosslinks are functional? Above there was a talk of skin thickening that goes on between ages 2-12. Regarding tendons, there are 2 unhealthy extremes, one is them being too stiff, due to quickly accumulating AGEs, no doubt; the other is 'double jointed' people, who suffer disproportionately from dislocations of all sorts. The point is, what you call 'damage' may be functional. It's easier to see on an example of a tree (under which a unicorn is resting). According to you, the bark represents 'damage' and it would be good to remove it, but I'm afraid the unicorn would disagree
 

What? I didn't say that no data exists. You don't accept the data I've showed you; I'm not going to waste my time looking for more. What I did do in the above paragraph was demonstrate that you were wrong about the impossibility of "proving a negative". Taking a measurement isn't "proving a negative" any more than a gas gauge on "E" is proving a negative. It's just getting a measurement. If the percentage of crosslinks in tissue that shows linear crosslink accumulation in adults is flat over the 15-25 age range, then that would be a very interesting measurement. Based on existing data, I don't expect you to find it, but give it a shot.

The irony here is that you showed no "existing data" on which you base your assertions (other than that one and only study of 5). Otherwise, all you have to do is to present those studies. Instead, you're telling me how they should be run!

But I really, really had enough of this one and only study and from now on I will ignore your misrepresentations of it as "existing data" and "known science".

Edited by xEva, 07 February 2015 - 02:49 AM.

[HighDesertWizard]

 

 

Too bad it's so hard to tell what's the chicken and what's the egg. We do know that damage increases, because we have measured it as a function of age. We also know that paracrine signaling factors change with age. We are not 100% sure which is cause and which is effect, but all evidence I'm aware of favors damage as cause rather than effect.

I think you're right, niner, that Katcher and Mitteldorf make an extreme argument from some of the rejuvenation study evidence they cite. Still, damage was repaired, to some degree, as an effect from a change of circulation system context.

I asked up thread for an Explanation of those study effects from a Damage Theory point of view. No one, yet, has offered up such an explanation...

Can you provide one now?

 

I'm not sure exactly which rejuvenation study you're referring to; the parabiosis work?  At any rate, I think they are probably confusing "some things working better" with actual elimination of the most problematic damage, which I don't think is happening.  If paracrine signals that decline with age are brought back up via some form of external supplementation, that hasn't fixed damage, it's just changed the level of some signalling molecules.  The real question is why do those compounds decrease over time?  What drives that?  I can imagine such a thing happening either due to damage or to "programming".  If signals are dropping due to programming, then even if you fixed all the damage, you'd either have to figure out how to reverse the programming or defeat it via supplementation.   If you manage to successfully supplement the various paracrine signals in young blood, you won't get "young".  You will still have to figure out how to repair the damage, or you will be a trashed-out old dude with young blood...

 

@niner... Appreciate your reply... I did mean the parabiosis studies. I was thinking of some others too that were cited in the Katcher paper. But your arguments against him, niner, must have caught on because the full text source I had posted up thread is now not available...  At any rate...

 

I believe it unwise to so quickly dismiss the importance of those studies. I summarize why below. For now, let me put the point bluntly… Increasing evidence points to the importance of NF-kB in aging and NF-kB Inhibition for Longevity.

• Mitteldorf made the point that NF-kB increases in the circulation during aging. There are several cases to be made that this is true.

   

• In 2008 and 2009, some Finnish scientists published a set of studies about NF-kB and aging. They do something that is all too rare and that I like a lot… They describe their Explanation of Aging in terms of important other Explanations of Aging. They found that…

Different screening techniques have revealed that mammalian aging is associated with the activation of NF-κB transcription factor system. The NF-κB system is an ancient host defense system concerned with immune responses and different external and internal dangers, such as oxidative and genotoxic stress. NF-κB signaling is not only the master regulator of inflammatory responses but can also regulate several homeostatic responses such as apoptosis, autophagy, and tissue atrophy.”

• In 2013, some Chinese scientists found that mechanistic “studies further revealed that IKK-β and NF-κB inhibit gonadotropin-releasing hormone (GnRH) to mediate ageing-related hypothalamic GnRH decline, and GnRH treatment amends ageing-impaired neurogenesis and decelerates ageing.”

• Also, in Human and other Species studies, via the Vagus-CAIP-HRV Nexus, NF-kB is inhibited and Survivor Rates increased in those with high HRV. More importantly and practically, NF-kB can probably be increased by a diverse set of deliberate and conscious means I'm hoping to discuss at LongeCity. I have posted a good deal about this topic at LongeCity and I won’t hijack this thread by being redundant. Suffice it here to provide a link to 7 slides showing graphic figures from published studies that make the point. Those 7 slides are a part of the argument I'm making...  

To repeat the point I made above… The Rejuvenation Studies also implicate NF-kB as being important in aging and suggest that NF-kB reduction in the circulation might be usefully explored for its importance for increased Health and Longevity. (Getting across what Kurzweil calls Bridges 1 and 2.)

 

It seems premature and unwise to me to discount the importance of those studies.

Edited by HighDesertWizard, 07 February 2015 - 05:53 PM.

[corb]

To repeat the point I made above… The Rejuvenation Studies also implicate NF-kB as being important in aging and suggest that NF-kB reduction in the circulation might be usefully explored for its importance for increased Health and Longevity. (Getting across what Kurzweil calls Bridges 1 and 2.)

 

It seems premature and unwise to me to discount the importance of those studies.

 

 

NfkB is over-activated when tissues accumulate AGEs.

NAD+ is depleted when PARP is over-activated to compensate for genomic instability.

Inhibiting NfkB and PARP will not take care of the underlying problem, at best it will slow down pathologies.

If there is a programmed downreagulation it's upstream of NfkB and NAD. To begin with the ammount of NAD+ and NfkB change visibly in people in their 50s an up.

What drives aging up to that point?
 

[Kevnzworld]

To repeat the point I made above… The Rejuvenation Studies also implicate NF-kB as being important in aging and suggest that NF-kB reduction in the circulation might be usefully explored for its importance for increased Health and Longevity. (Getting across what Kurzweil calls Bridges 1 and 2.)

It seems premature and unwise to me to discount the importance of those studies.

NfkB is over-activated when tissues accumulate AGEs.
NAD+ is depleted when PARP is over-activated to compensate for genomic instability.
Inhibiting NfkB and PARP will not take care of the underlying problem, at best it will slow down pathologies.
If there is a programmed downreagulation it's upstream of NfkB and NAD. To begin with the ammount of NAD+ and NfkB change visibly in people in their 50s an up.
What drives aging up to that point?

A lot of things can activate NFKB, not just AGE accumulation. Managing it with anti inflammatory compounds may be a bandaid, but for now a necessary one given inflammation's implication in many aging pathologies.
You can add poorer methylation as one ages to the list. Lowering homocysteine with B vitamins controls that.
Hopefully NR can mitigate NAD depletion too.
The list of physiological functions that decline or become less efficient with increasing age is a long one. It isn't limited to failure of existing repair mechanisms or declining immune function, though all of it is probably interdependent and thus related,

[corb]

A lot of things can activate NFKB, not just AGE accumulation. Managing it with anti inflammatory compounds may be a bandaid, but for now a necessary one given inflammation's implication in many aging pathologies.

 

AGEs drive a good chunk of the inflammation as well.

 

 

From all the evidence presented in this review, it is obvious that the RAGE-ligands axis is closely linked to a broad range of diseases, all of which appear to exhibit upregulation and accumulation of one or more types of RAGE ligands. RAGE, expressed in many different cell types, interacts with a number of its ligands to model a complicated biochemical axis linking complex which in turn perpetuates and amplifies inflammatory responses and leads to the pathogenesis of various inflammatory-related diseases.

 

http://www.hindawi.c...ji/2013/403460/

 

B₃ and Aspirin is what my grandparents used to take. That didn't help them much.

Edited by corb, 08 February 2015 - 12:10 AM.

[niner]

Too bad it's so hard to tell what's the chicken and what's the egg. We do know that damage increases, because we have measured it as a function of age. We also know that paracrine signaling factors change with age. We are not 100% sure which is cause and which is effect, but all evidence I'm aware of favors damage as cause rather than effect.

I think you're right, niner, that Katcher and Mitteldorf make an extreme argument from some of the rejuvenation study evidence they cite. Still, damage was repaired, to some degree, as an effect from a change of circulation system context.

I asked up thread for an Explanation of those study effects from a Damage Theory point of view. No one, yet, has offered up such an explanation...

Can you provide one now?

 
I'm not sure exactly which rejuvenation study you're referring to; the parabiosis work?  At any rate, I think they are probably confusing "some things working better" with actual elimination of the most problematic damage, which I don't think is happening.  If paracrine signals that decline with age are brought back up via some form of external supplementation, that hasn't fixed damage, it's just changed the level of some signalling molecules.  The real question is why do those compounds decrease over time?  What drives that?  I can imagine such a thing happening either due to damage or to "programming".  If signals are dropping due to programming, then even if you fixed all the damage, you'd either have to figure out how to reverse the programming or defeat it via supplementation.   If you manage to successfully supplement the various paracrine signals in young blood, you won't get "young".  You will still have to figure out how to repair the damage, or you will be a trashed-out old dude with young blood...

 
@niner... Appreciate your reply... I did mean the parabiosis studies. I was thinking of some others too that were cited in the Katcher paper. But your arguments against him, niner, must have caught on because the full text source I had posted up thread is now not available... [/size][/background]

 At any rate...
 
I believe it unwise to so quickly dismiss the importance of those studies. I summarize why below. For now, let me put the point bluntly… Increasing evidence points to the importance of NF-kB in aging and NF-kB Inhibition for Longevity.
[ various refs]
 
To repeat the point I made above… The Rejuvenation Studies also implicate NF-kB as being important in aging and suggest that NF-kB reduction in the circulation might be usefully explored for its importance for increased Health and Longevity. (Getting across what Kurzweil calls Bridges 1 and 2.)
 
It seems premature and unwise to me to discount the importance of those studies.

I'm not dismissing or discounting any of this work; rather, I'm asking how these effects come about-- are they programmed, such that they would happen in the absence of any damage, or are they caused by damage?  (or is there a spectrum of effects, some of which are programmed and some of which are caused by damage?)

Salminen and Kaarniranta in their NF-kB paper say:
 

Moreover, Spencer et al. [16] and Poynter and Daynes [17] have demonstrated that dietary therapies with antioxidants and PPAR-α agonist can down-regulate the age-related increase in the DNA-binding activity of the NF-κB complex, as well as the increased expression of IL-6 and IL-12 cytokines.These observations imply that oxidative stress has a major role in the constitutive activation of the NF-κB system in tissues during aging.

Oxidative stress is upregulated by damaged mitochondria, so this is an example of how damage can trigger a change in a signalling factor. This doesn't mean that there aren't other "programmed" events that are independent of damage; I'm waiting for evidence that such a thing exists, but not specifically discounting it.

[addx]

@Cosmicalstorm

 

I am aware of the SENS strategies, but lack of inclusion of mtDNA into the nucleus isn't the reason why we age.

 

We do not age because biology is imperfect. We age because it makes sense from an evolutional viewpoint. We are designed to age.

 

I have a whole topic about ageing being "designed" 

 

http://www.longecity...n-in-evolution/

[HighDesertWizard]

 

To repeat the point I made above… The Rejuvenation Studies also implicate NF-kB as being important in aging and suggest that NF-kB reduction in the circulation might be usefully explored for its importance for increased Health and Longevity. (Getting across what Kurzweil calls Bridges 1 and 2.)

 

It seems premature and unwise to me to discount the importance of those studies.

 

 

NfkB is over-activated when tissues accumulate AGEs.

NAD+ is depleted when PARP is over-activated to compensate for genomic instability.

Inhibiting NfkB and PARP will not take care of the underlying problem, at best it will slow down pathologies.

If there is a programmed downreagulation it's upstream of NfkB and NAD. To begin with the ammount of NAD+ and NfkB change visibly in people in their 50s an up.

What drives aging up to that point?

 

Salminen and Kaarniranta in their NF-kB paper say:

 

Moreover, Spencer et al. [16] and Poynter and Daynes [17] have demonstrated that dietary therapies with antioxidants and PPAR-α agonist can down-regulate the age-related increase in the DNA-binding activity of the NF-κB complex, as well as the increased expression of IL-6 and IL-12 cytokines.These observations imply that oxidative stress has a major role in the constitutive activation of the NF-κB system in tissues during aging.

Oxidative stress is upregulated by damaged mitochondria, so this is an example of how damage can trigger a change in a signalling factor. This doesn't mean that there aren't other "programmed" events that are independent of damage; I'm waiting for evidence that such a thing exists, but not specifically discounting it.

 

Oxidative Stress is upstream of NF-kB activation. It’s also downstream of it so NF-kB inhibition implicates less oxidative stress. Eradication of aging requires that something be done about AGEs. We agree.

 

But my thinking has evolved about Bridge 1 and 2 anti-aging strategies and I'm trying to think through the larger significance and practical implications of the graphic figures from those studies I assembled in a set of slides.

 

The Healthful Functions of the Vagus-CAIP-HRV Nexus are a positive Evolutionary Adaptation in Humans. The Settled Science of the Vagus-CAIP-HRV Nexus makes clear that these functions can enable us to prevent or slow morbidity and eventual mortality. That said, as shown in the first two slides, these functions are degraded during aging on account of damage to Vagus-CAIP signaling.

 

The upshot... Vagus-CAIP-HRV Signaling, itself, turns out to need repair over time, . That's why bringing this up is on-topic in this thread.

 

Now... Consider this... Evolution has Selected for the Vagus-CAIP-HRV Nexus developing means, that we can consciously trigger, to Simulate its healthful functional behavior as if it had not been damaged.

 

Anatomical, functional, and molecular lesions in the vagus nerve enhance cytokine production associated with nonresolving inflammation. Under basal conditions, the vagus nerve transmits tonic inhibitory activity that dampens the activity of the innate immune response to pathogen associated molecular products. The inhibitory activity of the inflammatory reflex can be enhanced by methods that increase the generation of adrenergic signals in the splenic nerve. This has been accomplished experimentally by electrically stimulating the vagus nerve, by electrically stimulating the splenic nerve directly, or by pharmacologically activating the adrenergic splenic neurons using cholinergic agonists. 

 

Fredrickson and Epel, among several others have shown that various states of Cognition, including "Positive Cognition" and/or Mindfulness increase HRV. Consider the meaning of that fact...

 

Evolution in Humans has been Selecting for Increased, Conscious, Cognitive manipulation of Our Physical Health through means which Simulate Healthy Vagus-CAIP signaling.

 

I'm not suggesting that current capabilities associated with the Vagus-CAIP-HRV Nexus will overcome the maximum human lifespan to date. Obviously, that will require something more. I am suggesting that, in the Vagus-CAIP-HRV Nexus itself, we have potential capabilities, yet unexplored, to get across what Kurzweil calls Bridges 1 and 2 for radical life extension.

Edited by HighDesertWizard, 08 February 2015 - 06:53 PM.

[addx]

Not sure if this came up, stumbled upon it

http://www.ncbi.nlm....les/PMC2716045/

A soma-to-germline transformation in long-lived C. elegans mutants

"Unlike the soma which ages during the lifespan of multicellular organisms, the germline traces an essentially immortal lineage. Genomic instability in somatic cells increases with age, and this decline in somatic maintenance might be regulated to facilitate resource reallocation toward reproduction at the expense of cellular senescence. We report here that C. elegans mutants with increased longevity exhibit a soma-to-germline transformation of gene expression programs normally limited to the germline. Decreased insulin-like signaling causes the somatic misexpression of germline-limited pie-1 and pgl family of genes in intestinal and ectodermal tissues. DAF-16/FoxO, the major transcriptional effector of insulin-like signaling, regulates pie-1 expression by directly binding to the pie-1 promoter. The somatic tissues of insulin-like mutants are more germline-like and protected from genotoxic stress. Gene inactivation of components of the cytosolic chaperonin complex that induce increased longevity also cause somatic misexpression of PGL-1. These results suggest that the acquisition of germline characteristics by the somatic cells of C. elegans mutants with increased longevity contributes to their increased health and survival."


and

this seems kinda related as well

http://www.ncbi.nlm....les/PMC3098679/

The Stress of Protein Misfolding: From Single Cells to Multicellular Organisms

The cell nonautonomous regulation of stress responses by neurons has recently gained support from another study showing that the mitochondrial stress response, central to regulating longevity, is also under cell nonautonomous control (Durieux et al. 2011). Cell nonautonomous regulation of chaperones may in fact be a more general feature of metazoan control, although the type of regulation itself may differ based on the ecology and life history of the organism (Feder and Hofmann 1999). In this regard, restraint stress in rodents (Blake et al. 1991; Fawcett et al. 1994) results in activation of the hypothalamic-pitutary-adrenal axis and ACTH-dependent up-regulation of specific HSPs in the thoracic aorta, endothelial cells, and adrenal cortex of rats. This induction of HSPs is HSF1-dependent and markedly declines with age



In my threads where I prove ageing evolved rather than being a mistake, I do actually propose exactly that: the nervous system of animals is the primary regulator of ageing.

Maturing, ageing, mutation rate is "species level adaptation" meaning they are intelligent mechanisms rather than accidental mistakes of evolution. Evolution itself is intelligent as it responds to conditions and adapts the species as if it was God.

Edited by addx, 09 February 2015 - 04:19 PM.

[LeeYa]

Not sure if this came up, stumbled upon it

http://www.ncbi.nlm....les/PMC2716045/

A soma-to-germline transformation in long-lived C. elegans mutants

"Unlike the soma which ages during the lifespan of multicellular organisms, the germline traces an essentially immortal lineage. Genomic instability in somatic cells increases with age, and this decline in somatic maintenance might be regulated to facilitate resource reallocation toward reproduction at the expense of cellular senescence. We report here that C. elegans mutants with increased longevity exhibit a soma-to-germline transformation of gene expression programs normally limited to the germline. Decreased insulin-like signaling causes the somatic misexpression of germline-limited pie-1 and pgl family of genes in intestinal and ectodermal tissues. DAF-16/FoxO, the major transcriptional effector of insulin-like signaling, regulates pie-1 expression by directly binding to the pie-1 promoter. The somatic tissues of insulin-like mutants are more germline-like and protected from genotoxic stress. Gene inactivation of components of the cytosolic chaperonin complex that induce increased longevity also cause somatic misexpression of PGL-1. These results suggest that the acquisition of germline characteristics by the somatic cells of C. elegans mutants with increased longevity contributes to their increased health and survival."

 

 

An interresting paper. Maybe a blueprint for life-extension strategies in humans?

 

However, metabolism-related gene "transformation" like DAF-16 or insulin signalling is not as promising as soma-to-germline transformation of constitutionally activated repair mechanisms.
 

 

 

I have a whole topic about ageing being "designed" 

http://www.longecity...n-in-evolution/

 

 

Thank you for pointing at this interresting thread. Do you think that there is evidence that opioid signalling is able to impact (reactivate) repair?

[xEva]

Oh so you did not like my post lol. Too bad, really, 'cause I did not like you stressing in every other post that data showing accumulation of damage <25 exists, but you can't be bothered looking for it. I bet you (and others) looked pretty hard, but all you could find were those 5 sample poitns.

And it's creepy that the Katcher paper that HighDesertWizard uploaded disappeared -- without any mention of who did it and why. Makes me wonder if during your extensive search you guys intentionally overlooked the papers with disagreeable data. I suppose a while from now, when it will become clear to all that SENS' dismissal of our inherent repair mechanisms as irrelevant was wrong, this thread will also quietly disappear Such silly attempts at 'damage control' is what ideology does to otherwise intelligent people. Sad, really.

 

Regarding the "rejuvenation" from fasting that doesn't last in older people, that's because the "rejuvenation" didn't eliminate the damage, or at least not enough of it. The damage that was still present caused the elderly fasters to rapidly deteriorate. You haven't said exactly what this rejuvenation consists of, so we can really only speculate about it, but I can assure you that fasting will not make elderly skin youthful again.

I believe that a large part of the damage typical of aging is due to deposition of amyloids, which you can see as aging of the skin in form of various growths and color changes. Amyloids are frequently mentioned when discussing the very old, but this aspect of aging is often ignored even in the middle-aged, presumably because (1) not much can be done about it at the moment and (2) mild forms of amyloidoses are generally not recognized until they become obvious gross pathology. But changes in the skin that are characteristic of amyloid deposits can start pretty early, often due to chronic subclinical infections -- though usually such changes are attributed entirely to photodamage. But I believe that the sun only exacerbates the primary damage due entirely to amyloids.

And so of course long-term fasting rapidly removes much of amyloid deposits (since the body is actively looking for sources of protein). This results in obvious rejuvenation of the skin, but! If the primary cause of active amyloid deposition was not dealt with --and one of them could be a chronic viral infection-- then the skin changes can quickly return -- very quickly! (other than subclinical chronic infections, the other source of amyloids is diet or whatever results in chronic inflammation).

[HighDesertWizard]

To be clear... I didn't upload the Katcher paper, although, now, I wish I had. It was posted to another another site and I merely provided a link to it. The link I provided now triggers an error. I'll write Mitteldorf and see if I can't get a soft copy for posting somewhere.

I think the acrimony in this thread is unfortunate, especially because Fredrickson and Epel and others have demonstrated that Positive Emotions and Cognition triggers higher Vagal Tone implicating the trigger of the Cholinergic Anti-inflammatory Pathway.

I believe SENS enthusiasts are obviously and primarily responsible for making the disagreements personal with continuing personal insults on xEva that is now triggering her/him to respond in kind. This, after she explicitly asked, early on, that the adhominim personal insults stop.

Let's be clear, when we make attack on personality rather than discuss these issues in smart and empathetic ways we trigger Sympathetic Nervous System negative emotions that create stress in ourselves and others, thus demonstating that we either don't care about others or don't have control of our personal identities.

I am more committed now to more graceful and empathetic confrontation in this great discussion when I feel the need to confront.

☺.

Edited by HighDesertWizard, 10 February 2015 - 03:50 PM.

[xEva]

Ok I misunderstood you about the Katcher paper missing. I could swear I saw it uploaded somewhere here. Maybe I saw into the future? Here it is:

Attached Files

•  Katcher_2013.pdf   337.89KB   26 downloads

[corb]

The only person that could benefit from taking down Katcher's paper is Katcher himself.

 

 

 

Time to include saline in your anti aging regiments,  some of the saline treated mice live a good 5-6 months more than the average.

[xEva]

@corb:
and what's the point of the graph you posted? It, along with the missing ref, belongs in another thread. (isn't it from the 2014 Ukrainian paper?)

@Kevnzworld:
I understand what you're getting at (ever so diplomatically ) You're saying that fixing whatever 'damage' will not result in all other things suddenly becoming right, like hormones, etc. That's a very good point. Though, at the moment, to me it still looks like those mysterious 'youth factors' may end up fixing everything, from nuclear damage --and these data are already in-- to ECM, like reducing heart hypertrophy (both from parabiosis studies).


@addx:
don't know who clicked you red this time. I found both refs interesting and in accord with the topic. That "acquisition of germline characteristics by the somatic cells" resulting in "increased health and survival" is very telling -- and yet it did not make those worms immortal. So, what killed them in the end?

And those misfolded proteins have been a neglected topic in aging. Don't know how much they differ from amyloids or even prions, but when they accumulate, pathology is very similar -- and glycated, they become niner's anathema of which he speaks whenever the topic of damage comes up. It's true though. All those messed up proteins represent a serious problem. That's what kills the very old in the end.

Edited by xEva, 10 February 2015 - 09:43 PM.

[corb]

@corb:
and what's the point of the graph you posted? It, along with the missing ref, belongs in another thread. (isn't it from the 2014 Ukrainian paper?)

 

You made a big deal out of his paper missing so I'm telling you if someone took down his papers it's Katcher himself. Papers are hosted on educational institutions and scientific journals. Once it's published only the author can remove it. Unless someone sues him, but the article in question was a review so nothing in it that would warrant suing over.

 

And you were the first to mention paracrine factors, xEva. Couple of posts back.

[Kevnzworld]

@corb:
and what's the point of the graph you posted? It, along with the missing ref, belongs in another thread. (isn't it from the 2014 Ukrainian paper?)

@Kevnzworld:
I understand what you're getting at (ever so diplomatically ) You're saying that fixing whatever 'damage' will not result in all other things suddenly becoming right, like hormones, etc. That's a very good point. Though, at the moment, to me it still looks like those mysterious 'youth factors' may end up fixing everything, from nuclear damage --and these data are already in-- to ECM, like reducing heart hypertrophy (both from parabiosis studies).

Ramadan fast is not a continuous fast that lasts for days or weeks. Instead, it's a dry fast from sunup to sundown, with plenty of eating and drinking during the night. But the studies of monks, who did regular long fasts, showed them living well into their 90s in far better health and mental ability than their lay counterparts.
.

Re: monks vs lay counterparts:
One would expect that given their vow of abstinence , meditation, and overall healthier lifestyle ( fasting included ). However, because many or most lived until their 90's ( assuming that's true ) doesn't implicate fasting specifically. Living until ones '90's ISNT extraordinary. If fasting activated " mysterious youth factors that could fix everything " , one would have expected lifespans well beyond 100.
There are a few threads on longecity concerning NAD depletion during aging and it's implication for cellular and immune health. I can't see any mechanism where fasting will restore NAD levels in the aging.
Hormones affect every bodily function either directly or tangentially. Their decline over time, and the resulting damage incurred can't be remedied by fasting IMO .
That being said, I do see the value of periodic fasting as both a cleansing and restorative tool.

[xEva]

this thread is plagued by misunderstandings it seems   
 

Re: monks vs lay counterparts:
One would expect that given their vow of abstinence , meditation, and overall healthier lifestyle ( fasting included ). However, because many or most lived until their 90's ( assuming that's true ) doesn't implicate fasting specifically. Living until ones '90's ISNT extraordinary. If fasting activated " mysterious youth factors that could fix everything " , one would have expected lifespans well beyond 100.
There are a few threads on longecity concerning NAD depletion during aging and it's implication for cellular and immune health. I can't see any mechanism where fasting will restore NAD levels in the aging.
Hormones affect every bodily function either directly or tangentially. Their decline over time, and the resulting damage incurred can't be remedied by fasting IMO .
That being said, I do see the value of periodic fasting as both a cleansing and restorative tool.

Kevnzworld, you combined 2 of my posts, from different dates and on different topics, into one misleading looking quote and then attributed to me ideas I never espoused. Why?

The Key phrase about the monks was not that they lived well into their 90s, but that they did it "in far better health and mental ability than their lay counterparts". I am well aware that living into one's 90s "ISNT extraordinary". My grandmas did just that without any special diets, supplements, or meditations, except maybe CR, which was mostly involuntary, btw.

Regarding you not seeing "any mechanism where fasting will restore NAD levels in the aging," that too is a common sentiment in this thread, especially dear to niner. Considering that you appear to know very little about fasting, this is not surprising. Finally, fasting as "cleansing and restorative tool"? really? you sound like an old school hygienist.

But this thread is not about fasting, but about our innate repair mechanisms. Fasting does not "cleanse" or "restore", but upregulates the most effective repairs, starting with all forms of autophagy. And I don't know what made you think that anyone here claimed that fasting could activate "mysterious youth factors that could fix everything". Up the thread, twice I brought up the little known fact that fasting effects appear to diminish with age, most likely due to those 'mysterious youth factors' missing in an old organism, making it revert to its old familiar self soon after refeeding, despite the fast's obvious repairs. That was said in the context that repairs a la SENS will likely face the same fate, unless those factors are identified and supplied.

Edited by xEva, 11 February 2015 - 10:06 PM.

[LeeYa]

Fasting is a reliable and safe intervention for reactivating repair mechanisms. Even if there would be a SENS-technology breakthough right now, it would take quite a few decades to reach a safety level close to a fast.

 

Unfortunately, fasting only induces a short-term and incomplete repair activation.

Edited by LeeYa, 12 February 2015 - 08:40 AM.

[Danail Bulgaria]

So, SENS technology is going slow, and fasting is with a short term and incomplete results. What shall we do, then?

 

Why not turn at stem cells and repair of the tissues and the organs via the stem cells?

[Kevnzworld]

So, SENS technology is going slow, and fasting is with a short term and incomplete results. What shall we do then?

Don't let the perfect be the enemy of the good.
Employing all the knowledge and tools currently available is better than waiting for technology that may never exist in our lifetime .
1) restrict caloric intake sensibly ( not fanatically)
2) exercise moderately
3) limit sugar intake, and take supplements shown to reduce and mitigate glycation.
4) take metformin
5) take natural anti inflammatory sups
6). Improve and monitor methylation
7) augment and maintain NAD levels ( NR, resveratrol)
8). Maintain youthful hormone status with bio identical hormones
9) take mitochondrial antioxidant/ biogenesis compounds ( pqq, c60, mitoq )
10) maintain an elevated vitamin D status
11). Hope for better science in our lifetime
12) enjoy everyday that we are lucky enough to live

[Kevnzworld]

Re: Autophagy,
( Aging as a progressive failure of existing repair mechanisms ) Methods to maintain autophagy in an aging person. This is a good review of the current state of the science with practical suggestions for enhancement.
http://www.anti-agin...fights-aging-2/

[xEva]

Unfortunately, fasting only induces a short-term and incomplete repair activation.

 

So, SENS technology is going slow, and fasting is with a short term and incomplete results.

I'm afraid I unwittingly created a wrong impression about declining benefits of fasting with age. The effects of a long-term fast are phenomenal in people under 55. 55-65 is when they they become noticeably transient. Caution is advised for people over 70 and it's not recommended to start fasting for people over 80.

Thanks Kevnzworld for the link to the article of the importance of autophagy. But do you know that fasting is the most effective inducer of all forms of autophagy known? That's indisputable fact.

Speaking of autophagy, I just finished reading Chemical Inducers of Autophagy That Enhance the Clearance of Mutant Proteins in Neurodegenerative Diseases, 2010 that someone linked recently around here. I've taken some of the compounds mentioned and this article confirmed my long-standing observation that when autophagy is induced, the appetite disappears. So you see, autophagy always comes with fasting, be it voluntary, due to lack of appetite, or forced, "'cause it's good for you". In this regard I'm curious how various appetite suppressors work, because those that induce autophagy seem like a good 'supplement' to take at the onset of a fast.


So, that fasting unleashes our most effective innate repairs that actually work is a fact. That these effects become transient with age is also a fact. It was noted long ago and even Shelton speaks about it in his Fasting Can Save Your Life, 1964, when he brings up the opponents' argument that fasting cannot be an anti-aging strategy, because the effects last only in younger people (again, here 'younger' is under 70). These two facts carry a serious implication for future SENS repairs, meaning, they are unlikely to last in the very old either.

Edited by xEva, 13 February 2015 - 02:17 PM.

[Danail Bulgaria]

With fasting or not, human dies. This is not enough to be immortal. Fast if you want. But also develop the really important technologies - the medicine, the therapeutic cloning, the stem cells.

[niner]

So, that fasting unleashes our most effective innate repairs that actually work is a fact. That these effects become transient with age is also a fact. It was noted long ago and even Shelton speaks about it in his Fasting Can Save Your Life, 1964, when he brings up the opponents' argument that fasting cannot be an anti-aging strategy, because the effects last only in younger people (again, here 'younger' is under 70). These two facts carry a serious implication for future SENS repairs, meaning, they are unlikely to last in the very old either.

 

If these two facts are due to the increasing damage done by the Senescence Associated Secretory Phenotype, or SASP (senescent cells secrete pro-inflammatory factors that damage surrounding tissue), then SENS repairs might last longer than you think, and maybe SENS will even make fasting work in the elderly.  The removal of unwanted senescent cells is likely to be the first SENS technology to make it into the clinic.

[Logic]

If these two facts are due to the increasing damage done by the Senescence Associated Secretory Phenotype, or SASP (senescent cells secrete pro-inflammatory factors that damage surrounding tissue), then SENS repairs might last longer than you think, and maybe SENS will even make fasting work in the elderly.  The removal of unwanted senescent cells is likely to be the first SENS technology to make it into the clinic.

"...it is also now evident that senescent cells can be cleared in vivo through an innate immune response. In fact, senescent cells have been reported to express ligands for cytotoxic immune cells, such as natural killer cells, that may permit the immune system to specifically target senescent cells and kill them in vivo..."
http://www.longecity...ndpost&p=713299

[Mind]

Relevant to the subject of this thread is the SENS question of the month: http://www.sens.org/...early-detection

 

The answer discusses the accumulation of damage throughout life. This was brought up earlier in the thread...does damage affect repair mechanisms, or is there some sort-of program that shuts down repair mechanisms. I suspect the damage comes first and it is why repair mechanisms fail.

[xEva]

 

Would you happen to have the reference for the paper that says damaged mitochondria don't engage in the starvation-driven fusion?  I looked but didn't see it.  I'm not anti-fasting, and if a non-lethal fast can rejuvenate mitochondria, I'm interested.  If this does turn out to be the case, it doesn't mean that SENS is wrong, nor does it mean that a method to repair mitochondria that was easier than fasting would be a bad thing, particularly for the frail elderly.

I will look for the papers on mitochondrial fission and fusion.

 

I just bumped on one review-kinda comment on the subject on my desktop. Here is the link to it Culling sick mitochondria from the herd, 2010. It's not quite about starvation, but the refs section should have relevant studies. Enjoy  [this education moment was brought to you by xEva]

[LeeYa]

'DNA spellchecker' means that genes aren't all equally likely to mutate
www.sciencedaily.com/releases/2015/02/150223142354.htm