Re: Thoughts on Creatine -Mitochondrial Protection and thyroid

[Guest guest]

It seems that intense excercise itself is very damaging to the

mitochondria, as the following shows. Lactic acid build up is maybe a

culprit as it seriously interferes with energy production, as anyone

knows after experincing the swelling and fatigue of muscles after

exertion. The many experiments in which sodium bicarbonate was given

prior to exercise have shown that the stuff may act to constitute a

buffer delaying lactic acid formation by increasing alkalosis and

tissue carbon dioxide. Personally, I find that carbonated water is a

much better, reinvigorating sport drink than many commercially

available sport drinks.

Muscle Nerve. 1999 Feb;22(2):258-61.

Acute exercise causes mitochondrial DNA deletion in rat skeletal

muscle.

Sakai Y, Iwamura Y, Hayashi J, Yamamoto N, Ohkoshi N, Nagata H.

Department of Physical Therapy, Ibaraki Prefectural University of

Health Sciences, Japan.

The present study was conducted to determine the effects of acute

overload exercise on mitochondrial DNA and the structure of skeletal

muscles. Rats were forced to run for 20 min until reaching complete

exhaustion. We detected the large-scale deletion (7052 bp) of

mitochondrial DNA by the nested polymerase chain reaction, and also

observed mitochondrial ultrastructural changes in the soleus muscle.

PMID: 10024140 [PubMed - indexed for MEDLINE]

The articles on lactic acid, carbon dioxide and sodium bicarbonate's

effects on athletic performance are legion. People do love repeating

the same experiments over and over.

Med Sci Sports Exerc. 2005 May;37(5):759-67.

Effects of induced metabolic alkalosis on prolonged

intermittent-sprint performance.

Bishop D, Claudius B.

Team Sport Research Group, School of Human Movement and Exercise

Science, The University of Western Australia, Crawley, WA, Australia.

dbishop@...

PURPOSE: Previous studies have shown that induced metabolic

alkalosis, via sodium bicarbonate (NaHCO3) ingestion, can improve

short-term, repeated-sprint ability. The purpose of this study was to

assess the effects of NaHCO3 ingestion on a prolonged,

intermittent-sprint test (IST). METHODS: Seven female team-sport

athletes (mean +/- SD: age = 19 +/- 1 yr, VO2peak = 45.3 +/- 3.1 mL x

kg(-1) x min(-1)) volunteered for the study, which had received ethics

clearance. The athletes ingested two doses of either 0.2 g x kg(-1) of

NaHCO3 or 0.138 g x kg(-1) of NaCl (placebo), in a double-blind,

random, counterbalanced order, 90 and 20 min before performing the IST

on a cycle ergometer (two 36-min " halves " of repeated approximately

2-min blocks: all-out 4-s sprint, 100 s of active recovery at 35%

VO2peak, and 20 s of rest). Capillary blood samples were drawn from

the ear lobe before ingestion, and before, during, and after each half

of the IST. VO2 was also recorded at regular intervals throughout the

IST. RESULTS: Resting plasma bicarbonate concentration ([HCO3-])

averaged 22.6 +/- 0.9 mmol x L(-1), and at 90 min post-ingestion was

21.4 +/- 1.5 and 28.9 +/- 2.8 mmol x L-1 for the placebo and NaHCO3

conditions, respectively (P < 0.05). Plasma [HCO3-] during the NaHCO3

condition remained significantly higher throughout the IST compared

with both placebo and pre-ingestion. There was a trend toward improved

total work in the second (P = 0.08), but not first, half of the IST

after the ingestion of NaHCO3. Furthermore, subjects completed

significantly more work in 7 of 18 second-half, 4-s sprints after

NaHCO3 ingestion. CONCLUSIONS: The results of this study suggest that

NaHCO3 ingestion can improve intermittent-sprint performance and may

be a useful supplement for team-sport athletes.

PMID: 15870629

BUT the most important factor in terms of mitochondria activity

regulation seems to be THYROID HORMONE. Hypothyroidism is perhaps an

indication of mitochondrial damage and respiratory impairment.

J Mol Endocrinol. 2001 Feb;26(1):67-77.

Thyroid hormone action in mitochondria.

Wrutniak-Cabello C, Casas F, Cabello G.

UMR Differenciation Cellulaire et Croissance (INRA, Universite

Montpellier II, ENSAM), Unite d'Endocrinologie Cellulaire, INRA, 2

Place Viala, 34060 Montpellier Cedex 1, France.

Triiodothyronine (T3) is considered a major regulator of

mitochondrial activity. In this review, we show evidence of the

existence of a direct T3 mitochondrial pathway, and try to clarify the

respective importance of the nuclear and mitochondrial pathways for

organelle activity. Numerous studies have reported short-term and

delayed T3 stimulation of mitochondrial oxygen consumption. Convincing

data indicate that an early influence occurs through an extra-nuclear

mechanism insensitive to inhibitors of protein synthesis. Although it

has been shown that diiodothyronines could actually be T3 mediators of

this short-term influence, the detection of specific T3-binding sites,

probably corresponding to a 28 kDa c-Erb Aalpha1 protein of the inner

membrane, also supports a direct T3 influence. The more delayed

influence of thyroid hormone upon mitochondrial respiration probably

results from mechanisms elicited at the nuclear level, including

changes in phospholipid turnover and stimulation of uncoupling protein

expression, leading to an increased inner membrane proton leak.

However, the involvement of a direct mitochondrial T3 pathway leading

to a rapid stimulation of mitochondrial protein synthesis has to be

considered. Both pathways are obviously involved in the T3 stimulation

of mitochondrial genome transcription. First, a 43 kDa c-Erb Aalpha1

protein located in the mitochondrial matrix (p43), acting as a potent

T3-dependent transcription factor of the mitochondrial genome, induces

early stimulation of organelle transcription. In addition, T3

increases mitochondrial TFA expression, a mitochondrial transcription

factor encoded by a nuclear gene. Similarly, the stimulation of

mitochondriogenesis by thyroid hormone probably involves both

pathways. In particular, the c-erb Aalpha gene simultaneously encodes

a nuclear and a mitochondrial T3 receptor (p43), thus ensuring

coordination of the expression of the mitochondrial genome and of

nuclear genes encoding mitochondrial proteins. Recent studies

concerning the physiological importance of the direct mitochondrial T3

pathway involving p43 led to the conclusion that it is not only

involved in the regulation of fuel metabolism, but also in the

regulation of cell differentiation. As the processes leading to or

resulting from differentiation are energy-consuming, p43 coordination

of metabolism and differentiation could be of significant importance

in the regulation of development.

PMID: 11174855

Exp Physiol. 2003 Jan;88(1):121-8.

Regulation of mitochondrial biogenesis by thyroid hormone.

Weitzel JM, Iwen KA, Seitz HJ.

Institut fur Medizinische Biochemie und Molekularbiologie,

Abteilung fur Biochemische Endokrinologie, Universitatsklinikum

Hamburg-Eppendorf, Hamburg, Germany. weitzel@...

Thyroid hormone (T3) has a profound effect on mitochondrial

biogenesis. T3-regulated gene expression is mediated by thyroid

hormone receptor (TR) binding to thyroid hormone response elements

(TREs). In concert with the action of various coactivators and

corepressors this interaction leads to a modulation of the chromatin

structure and subsequently to a modulation of gene expression of

adjacent target genes. However, as numerous genes are endogenously

regulated by T3, and a TRE appears to be absent in their regulatory

elements, a TR-independent pathway of T3-mediated gene regulation is

likely. In this review, we discuss the direct mechanisms of

TR-dependent regulation of gene expression on the nuclear and

mitochondrial genome by T3. We also summarise recent observations on

an indirect mechanism of T3 action via intermediate factor(s). We

discuss the regulation of nuclear respiratory factor 1 (NRF-1) and

peroxisome proliferator-activated receptor gamma coactivator 1 alpha

(PGC-1alpha) by T3, suggesting NRF-1 and PGC-1alpha as attractive

candidates for an intermediate factor of T3 action in vivo.

PMID: 12552316

Best regards,

>

> I found only this (searching creatine monhydrate and lifespan):

> Mahoney, J. a; Parise, Gianni b; Tarnopolsky, Mark A. c

Nutritional and exercise-based therapies in the treatment of

mitochondrial disease. Current Opinion in Clinical Nutrition &

Metabolic Care. 5(6):619-629, November 2002

> " Summary: There is no currently recognized treatment for

mitochondrial disease. Future clinical trials are needed, as well as

research into the potential for in-vitro screening of various

compounds within affected cells from patients. Until this time, an

accurate diagnosis will facilitate treatment on a case-by-case basis. "

>

> Regards

>

> [ ] Thoughts on Creatine

>

>

> Hi, I'm a newbie post, so I hope my post is in compliance with your

> guidelines. Thanks for your patience.

>

> I'm wondering if Creatine could be used to help anti-aging?

>

> Let's consider the mitochondria for a moment -- they are what creates

> ATP for your body in the first place. And we know that the very

> respiration process that they use to make the ATP can also fry the

> genes floating around in the mitochondria. This gradual self-damage to

> the mitochondria is considered to be a significant source of aging.

> The Reactive Oxidative Species (ROS) produced by the normal operation

> of your mitochondria gradually damage not only the mitochondria

> themselves, but as damage becomes sufficient, the ROS can even leak

> out into the rest of your cell and damage it too.

>

> But suppose you were to regularly take an external supplement of ATP,

> in the form of Creatine. Then your mitochondria might not have to work

> so hard to make it. This means less mitochondrial respiration, and

> thus likely less damage to mitochondrial genes over time.

>

> People are used to only thinking of taking Creatine for workouts,

> track meets, swim meets, sports games, dance class, etc, where sudden

> bursts of energy demand are required.

>

> But what if you were to just take small amounts of Creatine on a

> regular basis, independent of any workout considerations. Will it help

> you to make your mitochondria last longer?

>

> Wouldn't taking Creatine still be consistent with Calorie Restriction,

> since you're bypassing your whole metabolism to get your ATP directly

> from external intake? The whole point of Caloric Restriction is to

> deprive your metabolism of work, since that work causes wear and tear

> on your cells.

>

> We've all heard about the animal studies on CR and their superior

> life-extending results. What if the same tests were to be done under

> CR but also including the intake of Creatine as a supplement to the

> regular CR diet?

>

> I began thinking about this after my thoughts on Chondroitin/GAGs.

> After all, if you ingest pre-made complex/energetic molecules through

> your diet, rather than forcing your own metabolic processes to

> generate them, then you are creating less work for your metabolism.

> Less work for your metabolism means less production of ROS. And less

> production of ROS means less damage to your genome and cellular

> components.

>

> Comments, please?

>