Anti-aging science
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12-02-2014, 06:22 PM (This post was last modified: 12-02-2014 11:16 PM by GirlyMan.)
RE: Anti-aging science
(12-02-2014 05:09 PM)toadaly Wrote:  I always preferred the math oriented sciences.

Me too. I tried CHEM101 3 different times at uni. Dropped it all three times because I always got to the point where I said "You fuckers are just making this shit up now. This ain't chemistry this is alchemy." I did like mixing test tube 1 with test tube 2 and seeing if it turned blue or red. That was fun.

(12-02-2014 05:09 PM)toadaly Wrote:  It's hard for a layman to sort fact from fraud on this stuff. Even resveratrol, has failed attempts to reproduce the results in mice and rats. Curcumin, at least in the form of turmeric, seems to have health benefits even if it doesn't slow aging - and it's nice and flavorful too. The only one I'm aware of that (so far at least) doesn't cause cancer and seems to still be standing from an anti-aging perspective, is NAD?

Metformin I think is still standing but 1) it's a script in the US (although readily available online without a script and isn't classified as a controlled substance in the US so US Customs don't give a shit) and 2) it's cheap as shit, like $6.00 for a 30-day supply at my dose, that's like fucking free so there ain't no incentive for big pharma to invest in further longevity studies of it.

I focus my supplements around lowering my blood sugars and metformin, resveratrol, NAD and curcumin all show pretty solid evidence for that. The fact they are also of interest to life-extension researchers I find curious and maybe not so coincidental.

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13-02-2014, 03:39 PM
RE: Anti-aging science
When I first saw the title of this thread, I read it as "Anti-Gagging Science" Shocking


Cool stuff, but I was kinda disappointed. Big Grin

Excuse me, I'm making perfect sense. You're just not keeping up.

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14-02-2014, 06:50 AM (This post was last modified: 14-02-2014 06:55 AM by Youkay.)
RE: Anti-aging science
I watched the video:

1) "the parts list"/human genome project: To view genes as a "part list" is a ridiculous idea. Any phenotype or even any cellular mechanistic step is the result of complex interactions and inter-regulations between many different genes. Understanding the effect of each gene is incredibly difficult and is certainly not done by mapping the genome. But I appreciate that he had to dumb things down for the non-specialized audience.

2) mapping cellular networks: it is true that mapping intra-cellular networks has a great contribution to understanding biochemical principles. In fact, bioinformatics is a new and promising field in life-sciences to re-evaluate our current knowledge. Mapping biochemical networks does often re-establish known models, further solidifying them. But sometimes interesting new aspects emerge.

Speaking of 5% of all interactions, or 20% is silly though. It can be estimated by using some algorithms, but can never be shown conclusively. I think he is again using these kind of numbers to better illustrate the point to a non-specialized audience.

3) "disease map": A disease map is a very neat idea. It might in fact give us a better understanding on how diseases are interconnected. The most important part is to identify central hubs of the network, which can then be targeted by drugs. However, previous bioinformatic mapping results often revealed that central hubs are key players which had already been determined as such. Therefore, in my opinion, it is a neat idea with potential new insights. But I do not think that it will be groundbreaking.



The forum link you provided is quite nice, very agreeable and they make nice contributions. In fact, I found this one there: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2685272/

You should definitely read it. It is very extensive and comprehensible. A very good and accurate review. And after that, you might learn that saying "NAD reverses aging" is a hopeless exaggeration.

Quote:The major theories of aging (eg, the free radical theory (Harman 2003), the immunologic theory (Franceschi et al 2000a), the inflammation theory (Chung et al 2001), mitochondrial theory (Cadenas and Davies 2000)) are all specific of a particular cause of aging, providing useful and important insights for the understanding of physiological changes occurring with aging. However, a global view of them is needed when debating about a process which is still obscure in some of its aspects (Holliday 2006). In this context, the search for a single cause of aging (such as a single gene or the decline of a body system) has recently been replaced by the view of aging as an extremely complex, multifactorial process.

Fun "paradox": The higher the selection pressure, the slower evolution takes place.
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14-02-2014, 10:19 PM
RE: Anti-aging science
Well, I hope anybody who is sincerely interested in aging will read the link above...

Fun "paradox": The higher the selection pressure, the slower evolution takes place.
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15-02-2014, 12:09 AM
RE: Anti-aging science
(14-02-2014 10:19 PM)Youkay Wrote:  Well, I hope anybody who is sincerely interested in aging will read the link above...

It's very technical, but still understandable. Here's what I get from it regarding possible therapies shown to work in at least some organism
  • This antagonism between reproduction and longevity is supported by experiments in which the limitation of the reproduction by destroying germ line cells can extend life span in both Drosophila and Caenorhabditis elegans.
  • The only robust finding that a pharmacological antioxidant can extend longevity has been reported by Melov and colleagues (2000) in an animal model in demonstrating that EUK-134, a compound with both catalase and superoxide dismutase activities, significantly extends longevity in nematodes.
  • Although mild amounts of oxidative damage such as that experienced during exercise training (Davies et al 1982) may actually be the stimulus for physiological mitochondrial biogenesis, more severe, more extensive, or more prolonged oxidative damage is clearly toxic (Cadenas and Davies 2000).
  • Gene manipulations possible in laboratory animals appear to have limited potential for direct application in humans, although they do provide insight into important biological factors in longevity determination in model systems. In contrast, the potential of cell replacement therapy in reversing some of the adverse effects of aging appears to be substantial. Aging is accompanied by some loss of tissue function, which is at least partially due to either the age-related loss of cells from the tissue or an increased proportion of dysfunctional cells.
  • The finding that most of the cells expressing telomerase, instead of undergoing cellular aging, maintain a youthful state and proliferate indefinitely has opened new fields of research for a potential “anti-aging” intervention (Bodnar et al 1998; Vaziri and Benchimol 1998). Cells that have been supplied with an exogenous source of telomerase maintain a youthful state and proliferate indefinitely (Bodnar et al 1998). These “rejuvenated” cells are not only immortal, but they have also shown reversal of senescent characteristics (such as increased fragility and subepidermal blistering) (Funk et al 2000). Thus, the biological and potential medical consequences of telomerase expression appear to be highly significant.
  • Moreover, antioxidants maintain the integrity and function of membrane lipids, cellular proteins, and nucleic acids and the control of signal transduction of gene expression in immune cells. Not surprisingly, immune system cells usually contain higher concentrations of antioxidants than do other cells (Knight 2000), given the high percentage of polyunsatured fatty acids in their plasma membranes. Thus, the immune cell functions are strongly influenced by the antioxidant/oxidant balance and, therefore, the antioxidant levels play a pivotal role in maintaining immune cells I) in a reduced environment and II) in protecting them from oxidative stress, so to preserve their adequate functioning (Knight 2000).
  • Estrogen replacement therapy has been called the first true anti-aging therapy. However, no results have yet been reported of randomized studies that compare effects of this therapy with placebos, beginning at the menopausal transition, in women with no known preexisting coronary heart disease or dementia.

    It has been demonstrated that circulating levels of growth hormone drop with increasing age. It has also been shown that GH replacement in adults with pituitary disease and GH deficiency has beneficial effects on body composition, reducing fat and increasing lean body mass, muscle strength, and bone mass. Rudman and colleagues investigated whether GH injections in older men would restore muscle mass typical of younger men. They found that insulin growth factor (IGF)-1 levels did rise and that lean body mass increased while fat mass decreased, suggesting that GH injections did reverse the changes in body composition that were due to age and deconditioning.
  • A single chapter in this review is deserved by caloric restriction, the only nongenetic intervention that has consistently shown to slow the intrinsic rate of aging in mammals (Dirks and Leeuwenburgh 2006). It is defined by the reduction in caloric intake while maintaining essential nutrient requirements. Traditionally, experimental mammalian models of caloric restriction reduce caloric intake by ~40% of the adlibitum diet throughout the lifespan of the animal. This reduction has resulted in a 30%–40% increase in maximum lifespan (Weindruch et al 1986).

Most of this is impractical, but some of it is not:
- exercise
- caloric restriction
- antioxidant supplements (EUK-134 in particular)
- possibly hormone replacement therapies
- tolemerase (may cause cancer as well, but if you're 90, what the heck)

I didn't see any discussion in this article about NAD or the other substances girlyman posted.

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16-02-2014, 06:35 AM (This post was last modified: 16-02-2014 07:50 AM by Youkay.)
RE: Anti-aging science
Quote:This antagonism between reproduction and longevity is supported by experiments in which the limitation of the reproduction by destroying germ line cells can extend life span in both Drosophila and Caenorhabditis elegans.

Let me just elaborate a little more on that: What the "disposable theory of aging" says is that only traits that exhibit a positive effect on fitness prior to reproduction are selected for. Traits that have a negative effect on the individual post-reproduction are no longer under the pressure of selection and are freely distributed to the offspring. Telomerase is a beautiful example for this.

The experiment with Drosophila was this: They strictly controlled the time point at which Drosophila would mate by delaying the age of reproduction as much as possible. What they have found is that the later the Drosophila were allowed to reproduce, the longer the life span of the offspring became.

What do you think does that experiment tell us?

Quote:The only robust finding that a pharmacological antioxidant can extend longevity has been reported by Melov and colleagues (2000) in an animal model in demonstrating that EUK-134, a compound with both catalase and superoxide dismutase activities, significantly extends longevity in nematodes.

The model was a nematode, a worm. What this study shows is "proof of principle". Yes, by exposing them to quite high concentrations of EUK-134 -a polycyclic, synthetic molecule which catalyses the same reaction as catalase and superoxide dismutase- the life span of nematodes are increased slightly.

[Image: 5602197f6.gif]

What do you think might be valid criticism towards the experimental results and against this approach to prevent aging?

Quote:Although mild amounts of oxidative damage such as that experienced during exercise training (Davies et al 1982) may actually be the stimulus for physiological mitochondrial biogenesis, more severe, more extensive, or more prolonged oxidative damage is clearly toxic (Cadenas and Davies 2000).

Yeah. Did you understand the point as to why mitochondrial DNA is more prone to oxidative damage than nuclear DNA? And did you understand what important part of our proteome the mitochondrial DNA encodes for?

Quote:Gene manipulations possible in laboratory animals appear to have limited potential for direct application in humans, although they do provide insight into important biological factors in longevity determination in model systems. In contrast, the potential of cell replacement therapy in reversing some of the adverse effects of aging appears to be substantial. Aging is accompanied by some loss of tissue function, which is at least partially due to either the age-related loss of cells from the tissue or an increased proportion of dysfunctional cells.

As it says in the review, aging should rather be seen as a stochastic process and not as a programmed process. The genetic theory of aging is therefore quite controversial. Keep that in mind.

And even if scientists should be able to show that aging is also a programmed process, the point you have raised becomes important. Let me elaborate on that. What would the treatment look like? Gene therapy. And how does gene therapy work? First, we insert a particularly designed DNA into a retrovirus. Then we genetically modify embryonic cells and artificially fertilize a female.

I don't see that this will happen Big Grin


Quote:The finding that most of the cells expressing telomerase, instead of undergoing cellular aging, maintain a youthful state and proliferate indefinitely has opened new fields of research for a potential “anti-aging” intervention (Bodnar et al 1998; Vaziri and Benchimol 1998). Cells that have been supplied with an exogenous source of telomerase maintain a youthful state and proliferate indefinitely (Bodnar et al 1998). These “rejuvenated” cells are not only immortal, but they have also shown reversal of senescent characteristics (such as increased fragility and subepidermal blistering) (Funk et al 2000). Thus, the biological and potential medical consequences of telomerase expression appear to be highly significant.

But, telomerase activation is highly cancerogenous. I have explained previously why this is so. Would you like me to explain again?

Quote:Moreover, antioxidants maintain the integrity and function of membrane lipids, cellular proteins, and nucleic acids and the control of signal transduction of gene expression in immune cells. Not surprisingly, immune system cells usually contain higher concentrations of antioxidants than do other cells (Knight 2000), given the high percentage of polyunsatured fatty acids in their plasma membranes. Thus, the immune cell functions are strongly influenced by the antioxidant/oxidant balance and, therefore, the antioxidant levels play a pivotal role in maintaining immune cells I) in a reduced environment and II) in protecting them from oxidative stress, so to preserve their adequate functioning (Knight 2000).

Did you understand that?

And again. Treatment with anti-oxidants is not thought to be effective to positively affect this.


Quote:Most of this is impractical, but some of it is not:
- exercise
- caloric restriction
- antioxidant supplements (EUK-134 in particular)
- possibly hormone replacement therapies
- tolemerase (may cause cancer as well, but if you're 90, what the heck)

Exercise and caloric restriction, correct.
Antioxidant supplements, very controversial.
Hormone replacement therapies, very controversial and possibly unhealthy.
Telomerase activation, clearly cancerogenous.


NAD is part of the Mitochondrial theory of aging. And I do not think it is convincing.

Fun "paradox": The higher the selection pressure, the slower evolution takes place.
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16-02-2014, 12:36 PM (This post was last modified: 16-02-2014 07:27 PM by GirlyMan.)
RE: Anti-aging science
Thanks to both M'kay and ToadTheWetSprocket for continuing this interesting discussion. There are 3 or 4 other anti-aging threads here it might be interesting to merge into one if a mod can figure out how.

(14-02-2014 06:50 AM)Youkay Wrote:  A very good and accurate review. And after that, you might learn that saying "NAD reverses aging" is a hopeless exaggeration.
(16-02-2014 06:35 AM)Youkay Wrote:  Exercise and caloric restriction, correct.

Recall that I design my supplementation around lowering my sugars and just find it curious that many of the supplements which lower blood sugar are also being investigated by anti-aging researchers. Metformin, for example, may extend lifespan by effectively mimicking some of the effects of calorie restriction and some healthy people take it based on that speculation alone but that's not why I take it. I take it to control my sugars which is a more pressing and immediate concern.

(16-02-2014 06:35 AM)Youkay Wrote:  Hormone replacement therapies, very controversial and possibly unhealthy.

Estrogen therapy maybe. I mean that shit killed Alan Turing pretty fucking quick. But I been on testosterone replacement therapy going on a decade now. I monitor my PSA and hemoglobin quarterly to keep an eye out for prostate cancer and polycthemia which as far as I know are the main long-term risks of TRT. Without TRT I'd have the testosterone levels of a little girl and a limp dick to match. That can't be healthy either. Tongue

(16-02-2014 06:35 AM)Youkay Wrote:  Telomerase activation, clearly cancerogenous.

That's what scared my gut off of it straight away even without further elaboration.

As it was in the beginning is now and ever shall be, world without end. Amen.
And I will show you something different from either
Your shadow at morning striding behind you
Or your shadow at evening rising to meet you;
I will show you fear in a handful of dust.
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16-02-2014, 12:49 PM
RE: Anti-aging science
(16-02-2014 12:36 PM)GirlyMan Wrote:  Thanks to both M'kay and ToadTheWetSprocket for continuing this interesting discussion. There are 3 or 4 other anti-aging threads here it might be interesting to merge into one if a mod can figure out how.

If you link them I can do that for ya.

(31-07-2014 04:37 PM)Luminon Wrote:  America is full of guns, but they're useless, because nobody has the courage to shoot an IRS agent in self-defense
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16-02-2014, 01:20 PM
RE: Anti-aging science
(16-02-2014 12:49 PM)Revenant77x Wrote:  
(16-02-2014 12:36 PM)GirlyMan Wrote:  Thanks to both M'kay and ToadTheWetSprocket for continuing this interesting discussion. There are 3 or 4 other anti-aging threads here it might be interesting to merge into one if a mod can figure out how.

If you link them I can do that for ya.

These are relevant but I don't see how they could be stitched together. Maybe a sub-forum if there's enough interest? Up until now it's mainly just been myself and DeepThought interested in this.

Anti-aging science

Anti-Aging

Anti-Ageing on the Cheap

NF-kappaB Regulation and Ageing

Zat getting pissed at us again

New organ grown from stem cells


Do you take vitamins and other supplements?

Onnit supplements: real science, or woo?

As it was in the beginning is now and ever shall be, world without end. Amen.
And I will show you something different from either
Your shadow at morning striding behind you
Or your shadow at evening rising to meet you;
I will show you fear in a handful of dust.
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16-02-2014, 01:49 PM
RE: Anti-aging science
(16-02-2014 01:20 PM)GirlyMan Wrote:  
(16-02-2014 12:49 PM)Revenant77x Wrote:  If you link them I can do that for ya.

These are relevant but I don't see how they could be stitched together. Maybe a sub-forum if there's enough interest? Up until now it's mainly just been myself and DeepThought interested in this.

Anti-aging science

Anti-Aging

Anti-Ageing on the Cheap

NF-kappaB Regulation and Ageing

Zat getting pissed at us again

New organ grown from stem cells


Do you take vitamins and other supplements?

Onnit supplements: real science, or woo?

I can actually merge all the threads but honestly that would just be a clusterfuck. A subforum would probably be a bit over kill. What you could do is quote mine those threads and bring the relative posts into this conversation.

(31-07-2014 04:37 PM)Luminon Wrote:  America is full of guns, but they're useless, because nobody has the courage to shoot an IRS agent in self-defense
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