Exercise improves health by evoking 'recycling'

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dime
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Methionine restriction increases lifespan

Postby dime » Sun 15 May 2011 12:34

Methionione restriction in the diet seems to increase lifespan, at least in mice and fruit flies.
Such a restriction basically means less usable protein if I'm not wrong.

On this diet we anyway don't consume so much protein, let's say 50-60 high quality grams per day on average. I wonder whether further reducing this amount for let's say 20% would lead to longer life without bad side-effects. Hmm.. :)

http://en.wikipedia.org/wiki/Methionine ... estriction
http://www.telegraph.co.uk/health/healt ... -life.html
http://www.ncbi.nlm.nih.gov/pubmed/15924568
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RRM
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Re: Methionine restriction

Postby RRM » Wed 18 May 2011 15:55

dime wrote:Methionione restriction in the diet seems to increase lifespan
Starvation (caloric restriction) evokes proteolysis, the recycling of redundant cellular proteins.
This proteolysis is inhibited by amino acids, but more specifically methionine, which ...
"accounted for at least 75% of the effect of the complete medium, strongly indicating that in Tetrahymena methionine is the main regulator of step-down proteolysis, a process generally connected with autophagy in eukaryotic cells. The fact that one amino acid has such a drastic effect should make the system well suited for further investigations of the regulation of this process." Grinde B et al
I wonder whether further reducing this amount for let's say 20% would lead to longer life without bad side-effects.
Cystein is required for glutathione, and is derived from methionine, so i wouldnt lower methionine too much...
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Exercise improves health by evoking 'recycling'

Postby dime » Sat 02 Feb 2013 03:45

Interesting research on how exactly is exercise promoting health: http://www.economist.com/node/21543129
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Re: Exercise improves health by evoking autophagy

Postby RRM » Sat 02 Feb 2013 13:31

Very interesting.
Im guessing that intermittent fasting works similarly, as well as calory restriction,
as in both the body will break down dysfunctioning cellular structures for re-use.
So that autophagy may be related to longevity.
Im also guessing that keeping your body in a low-fat state will have similar effects as well.
Because keeping your body-fat % low, there will always be breakdown of tissue as well,
as the body will desperately try to keep its fat % above a certain minimum,
and as you are trying to keep/push your fat % down,
this will increasingly be at the expense of unused cells.
Let me do a quick search.
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Calorie restriction, recycling & lifespan

Postby RRM » Sat 02 Feb 2013 13:41

Yep:
In yeast: our findings show that autophagy is: (1) induced by calorie restriction (CR), (2) required for full extension of chronical lifespan by calorie restriction in most cases (depending on atg allele, strain, and leucine availability) and, (3) promotes mitochondrial respiration proficiency during aging under CR conditions. Aris JP
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Autophagy and longevity

Postby RRM » Sat 02 Feb 2013 13:47

Enzymes required for the breakdown of unused cells, the so-called " silent information regulator 2 -family"
are implicated in age-related disorders and longevity. Kitada M et al
Full free article

" Our findings provide compelling evidence that cellular fitness is accompanied by reduced global protein synthetic burden" (due to recycling evoked by calorie restriction) Price JC et al
Full free article

Aging of the heart is accelerated when autophagy is impaired. Dutta D et al

"our data suggested that long-term CR may preserve cardiac function ... and promote autophagy."Han X et al

"There is a striking similarity between the signalling aspects of these two processes". Both ageing and autophagy share several signalling components .... Ageing and ageing-mediated defective autophagy involve accumulation of lipofuscin accumulates with age, but also when autophagy is defective ... Nutritional deprivation and calorie restriction ... can enhance autophagy and increase lifespan. "Such striking similarities indicate that lifespan is strongly dependent on autophagy." Petrovski G et al
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Exercise & CP

Postby dime » Sat 02 Feb 2013 15:03

It could very well explain the exercise effect of increasing CP too, and why the effect goes away (CP lowers) some short time after you stop exercising.

Older and disfynctional mitochondria are replaced by new ones when exercising -> improved breathing.
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Autophagy and ω-6 PUFAs

Postby RRM » Tue 19 Feb 2013 08:24

ω-6 PUFAs activates autophagy, a cell recycling mechanism that promotes starvation survival and slows aging. Inactivation of C. elegans autophagy components reverses the increase in life span conferred by supplementing the C. elegans diet with these fasting-enriched ω-6 PUFAs." O'Rourke EJ
dime
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Re: Autophagy and ω-6 PUFAs

Postby dime » Tue 19 Feb 2013 08:34

Ooh that's a very good find, even though it's C. elegans! It looks like more and more studies are done to investigate this topic.
AA and DGLA, but not EPA induced autophagy:
We found that supplementation with AA and
DGLA, but not with EPA, was sufficient to activate
autophagy in ad libitum-fed C. elegans (Fig. 2B). AA or
DGLA supplementation did not affect C. elegans food
consumption (Supplemental Fig. S6), suggesting that v-6
PUFAs induce cellular responses characteristic of the
response to caloric restriction but do not actually induce
caloric restriction.
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Re: Autophagy and PUFAs

Postby RRM » Tue 19 Feb 2013 10:00

"Dietary DHA and EPA can be converted to their ethanolamine derivatives, docosahexaenoyl ethanolamine (DHEA) and eicosapentaenoyl ethanolamine (EPEA)
... we demonstrated the involvement of PPARγ in DHEA- and EPEA-induced autophagy" Rovito D et al

"EPA and DHA can form endocannabinoids that: (i) are ligands for CB(1/2) receptors and possibly TRPV-1, (ii) have non-receptor mediated bioactivity, (iii) induce cell cycle arrest, (iii) increase autophagy" Brown I et al
No pain, no gain? ...

"EPA can concomitantly induce autophagy" Fukei M et al

But also "EPA counteracts palmitate-mediated increase of autophagy of cardiac cells" Cetrullo S et al
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Re: Autophagy and PUFAs

Postby dime » Tue 19 Feb 2013 15:31

"Docosahexaenoic acid (DHA) has been reported to induce tumor cell death by apoptosis.
...DHA induces not only apoptosis but also autophagy.
We also observed that DHA-induced autophagy was accompanied by p53 loss." Jing et al.

"DHA did not induce ER stress but was the most potent inhibitor of apoB100 secretion, acting via stimulation of autophagy" Caviglia et al.
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Autophagy & lipid peroxidation

Postby RRM » Tue 19 Feb 2013 21:08

Enzymatic lipid peroxidation may be a key factor in autophagy,
with PUFA release from the membrane evoked by stress/damage/alterations as the trigger,
and the lipoxidation products processed by the lysozome ('digestion' of valuable nutrients).

Non-enzymatic lipid peroxidation may be a key factor in apoptosis,
a more messy operation with more colateral damage,
and the lipoxidation products being counteracted by serum anti-oxidants and processed by the liver (so that they become nutrients again).
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Re: Autophagy & lipid peroxidation

Postby RRM » Mon 25 Feb 2013 17:33

Cell damage increases lipid peroxidation.
Vascular damage and chronic arterial diseases increases exposure of vascular smooth muscle cells to specific growth factors.
These growth factors activate autophagy, preventing (non-enzymatic) lipid peroxidation-induced cell death in vascular smooth cells. Salabei JK et al
Similarly, nerve growth factors preserve cell integrity of neurons.
A lack of growth factors induces mitochondrial ROS and subsequent lipid oxidation (blocked by antioxidants). Kirkland RA et al
Autophagy prevents ROS-mediated cell death (apoptosis) Higdon AN, by up-regulating p38 and nuclear factor-kappa B activation. Cheng Y et al
Melatonin (an endogenous antioxidant) modulates autophagy Vega-Naredo I et al increasing superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and total glutathione (GSH) levels Eşrefoğlu M et al

autophagy is coregulated by 4-hydroxynonenal (HNE), a major product of omega-6 fatty acid peroxidation Guéraud F et al
Autophagy is inhibited (by 40%) by modifications caused by lipid peroxidation products HNE and malonaldehyde (MDA), which may contribute to cell dysfunction Krohne TU et al
Unsaturated lipid oxidation products HNE and acrolein activate autophagy
lipid peroxidation-derived aldehydes stimulate autophagy, which removes aldehyde-modified proteins.
Inhibition of autophagy precipitates cell death in aldehydes-exposed cells Hill BG et al

Brain aging is associated with a progressive imbalance between antioxidant defenses and intracellular concentrations of ROS,
as exemplified by increases in products of lipid peroxidation, protein oxidation, and DNA oxidation.
Autophagic proteolysis and sirtuin activity are downregulated by the insulin signaling pathway.
Impaired autophagic activity has been associated with neurodegeneration. Dröge W et al Full Free Article
That insulin inhibits autophagy makes sense, as autophagy is catabolic, and insulin metabolic.
Hence caloric restriction and exercise (both catabolic) evoke autophagy.
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Re: Exercise improves health by evoking 'recycling'

Postby Kasper » Tue 26 Feb 2013 20:35

RRM wrote:Autophagic proteolysis and sirtuin activity are downregulated by the insulin signaling pathway.
So low insulin sensitivity may be a factor in inhibiting autophagy right ?
About sirtuin:
Preliminary studies with resveratrol, a possible SIRT1 activator, have led some scientists to speculate that resveratrol may extend lifespan.[19] Further experiments conducted by Rafael de Cabo et al. showed that resveratrol-mimicking drugs such as SRT1720 could extend the lifespan of obese mice by 44%.[20] Comparable molecules are now undergoing clinical trials in humans.
http://en.wikipedia.org/wiki/Sirtuin
http://www.nature.com/news/sirtuin-prot ... ls-1.10074
Hence caloric restriction and exercise (both catabolic) evoke autophagy.
What sort of exercise ? Aerobic exercise ? Anaerobic exercise ? Is walking also evoking autophagy ?
dime
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Re: Exercise improves health by evoking 'recycling'

Postby dime » Tue 26 Feb 2013 22:20

In the article I posted in the first post, mice were running on a treadmill for 30-80 minutes.
But I think it would be a bit hard to get the full article: http://www.nature.com/nature/journal/v4 ... 10758.html

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