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Old 04-24-2003, 04:34 AM   #21
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Quote:
Originally posted by Tara
http://www.letsrun.com/forum/flat_re...&thread=117514mitochondrial biogenesis

All I have to say re: mitochondrial biogenesis as of now is: ?
I followed your link, but I think that the response given was far too specific for a neophyte to this area. But then again, he was referring to signalling and not the larger process of mitochondrial biogenesis.
Do you have a starting point (other than that reference) from whence a discussion about mt biogenesis can commence?
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Old 04-24-2003, 05:07 AM   #22
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As far as a starting point, this sums up my knowledge of mt biogenesis:

"Mitochondrial biogenesis, the process of how mitochondria are formed and maintained, generally includes two main aspects. Firstly, during cell division the organelle and its genome have to be replicated and their accurate distribution to the daughter cells has to be guaranteed. Secondly, the continuous synthesis, transport and assembly of mitochondrial macromolecules is essential for the proper function of mitochondria."
http://zoosun00.unifr.ch/Trypanos/MITBIO.html

Do you have any suggested references? I probably need some background before the specifics of signaling can be meaningful.

thanks...
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Old 04-24-2003, 05:13 AM   #23
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Here are a couple of references

Cameron-Smith D.
Exercise and skeletal muscle gene expression.
Clin Exp Pharmacol Physiol. 2002 Mar;29(3):209-13.


Adhihetty PJ, Irrcher I, Joseph AM, Ljubicic V, Hood DA. Plasticity of skeletal muscle mitochondria in response to contractile activity.
Exp Physiol. 2003 Jan;88(Pt 1):99-107.
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Old 04-24-2003, 06:51 AM   #24
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Mitochrondrial biogenesis in this case refers to the increase in mitochrondria in a muscle due to exercise. Its one of the mechanisms underlying training-induced improvements in muscle endurance/muscle oxidative capacity. There is a lot of work going into understanding the biochemical pathways involved, knowledge of which may be useful to physiologists and medical researchers for a number of reasons. See for example Study Could Lead to a Drug That Mimics the Benefits of Exercise, a press release describing the Wu et al (2002) paper that appeared in Science, that showed that an enxyme called CaMK plays an important role in regulating MB (abstract below).

The review cited by WOunded King looks good:

Quote:
Regularly performed exercise in the form of endurance training produces a well-established adaptation in skeletal muscle termed mitochondrial biogenesis. The physiological benefit of this is an enhanced performance of muscle when subject to endurance exercise. This is not only of great advantage for athletic endeavours, but it also clearly improves the quality of life of previously sedentary individuals and those involved in injury rehabilitation. Here we review the molecular basis for mitochondrial biogenesis in muscle, from the initial signals arising in contracting muscle, to the transcription factors involved in mitochondrial and nuclear DNA transcription, as well as the post-translational import mechanisms required for the synthesis of the organelle. We discuss specific protein components associated with reactive oxygen species production, and suggest some questions which remain unanswered with respect to the role of exercise-induced mitochondrial biogenesis in ageing, apoptosis and disease.
Adhihetty PJ, Irrcher I, Joseph AM, Ljubicic V, Hood DA. Plasticity of skeletal muscle mitochondria in response to contractile activity.
Exp Physiol. 2003 Jan;88(Pt 1):99-107.



Quote:
Endurance exercise training promotes mitochondrial biogenesis in skeletal muscle and enhances muscle oxidative capacity, but the signaling mechanisms involved are poorly understood. To investigate this adaptive process, we generated transgenic mice that selectively express in skeletal muscle a constitutively active form of calcium/calmodulin-dependent protein kinase IV (CaMKIV*). Skeletal muscles from these mice showed augmented mitochondrial DNA replication and mitochondrial biogenesis, up-regulation of mitochondrial enzymes involved in fatty acid metabolism and electron transport, and reduced susceptibility to fatigue during repetitive contractions. CaMK induced expression of peroxisome proliferator-activated receptor gamma coactivator 1 (PGC-1), a master regulator of mitochondrial biogenesis in vivo, and activated the PGC-1 gene promoter in cultured myocytes. Thus, a calcium-regulated signaling pathway controls mitochondrial biogenesis in mammalian cells.
Wu et al, Regulation of mitochondrial biogenesis in skeletal muscle by CaMK. Science 2002 Apr 12;296(5566):349-52.

Patrick
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Old 04-24-2003, 02:15 PM   #25
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Quote Godot, Your genetic endowment is all you have. Going beyond it is incomprehensible. Hell, most people don't even approach their potential by a couple of light years! To be idiomatic, training can only help you "unlock" your potential.
------------------------------



From my own practical point of view I believe it is the mind that puts limits on what you can achieve physically,

Once you start to look for an increase in performance whether it is endurance or speed, the pain factor enters into the equation. With training the body can go further towards achieving either of these goals, but the pain factor encourages jogging over short distances rather than sprinting or marathons. The majority of us prefer the easier option so we only achieve a fraction of what we are physically capable of.

In a large entry for a race it is said that about ninety five percent are there just to take part, three or four percent are there and hope to win with luck and if the conditions are right.
Maybe just one or two people will have done everything possible in training and are only there to win; they will be totally pd off if they come second.

Once upon a time we had another incentive to push our bodies to a physical limit and that was the goal of survival.

If you take away the incentives of the will to win or the will to survival, then our bodies have less reason to push beyond any pain barriers, so we fall short of our potential.


-------------------------------------
Quote ps418 But it does mean that because of genetic differences, individuals will respond to the training differentially. Genetics does contribute in many different ways to both actual and potential athetic ability.
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The difficulty is trying to find where your potential lays, I tried many sports unsuccessfully in my teens, At 33 I took up cycling reasonably well ridding geared bikes.

At 34 I started to ride a fixed wheel bike, which seems to find extremes in both slow twitch and fast twitch muscles.

A fixed wheel has only one gear, if the gear is too low that means your legs can peddle at speeds exceeding 200rpm, which I have done going down hill. When you go down hill there is the need to secure your feet to the pedals or they get thrown of the pedals.

If the gear is to high, it will require a certain amount of brute force to climb hills.

I did one ride of 1200K in 84 hours although that is not fast it included sleep and eating time. From memory it took around 230,000 peddle revs over a period of about 65 hours peddling time. And it was a hilly course.


The major goal was to finish inside a time limit as there where over two thousand people taking part, much of it became competitive.

Breathing was a major factor, the real exertion is putting the effort in to climb the hill. When you reach the summit you then have to learn to relax and get your breath back when you descend the other side at peddle speeds of 200rpm plus. This is to ensure your breathing is relaxed enough to start climbing again as soon as you hit the dip.

One moment you can be going really well and seem to be flying, then without warning tiredness sets in.


Did I reach my limits, or go beyond my limits in endurance or speed, and I would have to say no on both counts.

The body is strong but the mind is weak.

Peace

Eric
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Old 04-24-2003, 02:39 PM   #26
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hey thanks! Lots of good reading. You guys have been great.

"Phoenix" revealed the reference for the AMPK research...

-----------------------------------------------------------
Proc Natl Acad Sci U S A 2002 Dec 10;99(25):15983-7

AMP kinase is required for mitochondrial biogenesis in skeletal muscle in
response to chronic energy deprivation.

Zong H, Ren JM, Young LH, Pypaert M, Mu J, Birnbaum MJ, Shulman GI.

Howard Hughes Medical Institute and the Departments of Internal Medicine, Cell
Biology, and Cellular and Molecular Physiology, Yale University School of
Medicine, New Haven, CT 06510, USA.
-----------------------------------------------------------
Mitochondrial biogenesis is a critical adaptation to chronic energy deprivation,
yet the signaling mechanisms responsible for this response are poorly
understood. To examine the role of AMP-activated protein kinase (AMPK), an
evolutionarily conserved fuel sensor, in mitochondrial biogenesis we studied
transgenic mice expressing a dominant-negative mutant of AMPK in muscle
(DN-AMPK). Both DN-AMPK and WT mice were treated with beta-guanidinopropionic
acid (GPA), a creatine analog, which led to similar reductions in the
intramuscular ATPAMP ratio and phosphocreatine concentrations. In WT mice, GPA
treatment resulted in activation of muscle AMPK and mitochondrial biogenesis.
However, the same GPA treatment in DN-AMPK mice had no effect on AMPK activity
or mitochondrial content. Furthermore, AMPK inactivation abrogated GPA-induced
increases in the expression of peroxisome proliferator-activated receptor gamma
coactivator 1alpha and calciumcalmodulin-dependent protein kinase IV (both
master regulators of mitochondrial biogenesis). These data demonstrate that by
sensing the energy status of the muscle cell, AMPK is a critical regulator
involved in initiating mitochondrial biogenesis.
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Old 04-24-2003, 02:58 PM   #27
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“The body is strong but the mind is weak.”

Eric- Certainly psychology is a factor, but the body and mind are one in the same, no? Both a product of environment and genetics.
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Old 04-25-2003, 04:13 AM   #28
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Hello Tara,

Yes they are one and the same, but they seem to have opposing needs.

Peace

Eric.
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