Monday, April 14, 2008

Metabolism; mitochondria and uncoupling

Just a final couple of aspects of Nick Lane's ideas about mitochondria, diet and aging before I finally leave them alone. There are some factors which he suggests might be associated with longevity.

The first is high numbers of mitochondria per unit basal metabolism. This is the approach taken by birds and bats (which live far longer than similar sized non flight mammals). The metabolic rate needed for flight is such that resting metabolic rate can be met by the copious mitochondria running at tickover. This is effective at supplying energy without free radical leakage, especially with factor two taken on board. I don't think we'll ever get near to bird numbers of mitochondria, but upping the numbers doesn't seem like a bad idea. How about a few ketones to help?

The second is uncoupling proteins. These allow the hydrogen ion gradient in the mitochondria to be dissipated as heat. This in turn allows through flow of electrons down the electron transport chain, even if there are buckets of unused ATP hanging around. Through flow without obstruction means minimal sewer leakage, less free radicals, less apoptosis...

From this abstract, note that:

"Fatty acids are known to enhance mitochondrial uncoupling protein (UCP) activity"

No mention of glucose doing this! The point of the paper is that ketones do exactly the same thing. I don't see the need for frank ketonuria, but I do like to have ketones on tap for whenever they might be needed!

Peter

11 comments:

Stephan said...

speaking of uncoupling proteins, it looks like adult humans can uncouple muscle mitochondria for non-shivering thermogenesis:

http://www.ncbi.nlm.nih.gov/pubmed/18335051?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

Peter said...

Cool link. More interesting than brown adipose tissue in mice! And BAT is not without interest...

Peter

Paul said...

Interesting to see this mention of cold-induced physiological change. I read a paper abstract a few years ago where winter swimmers had higher levels of immune system cells (sorry I cannot google that one up right now). It's easy to overlook such things when focusing on food, I wonder how much of the big picture we are missing that we don't even know we're missing. I doubt many epidemiological studies have 'cold exposure' as a parameter!

Stephan said...

When I started eating LC, I noticed I became more cold-tolerant. I haven't turned the heat on in my room all winter, and it has gotten down to 46 F. More typically it's 50-55 F at night.

JohnN said...

This is an interesting subject. I suspect thermogenesis generated during low-carbing may come from processing the excess protein into glucose - it takes 10 ATP units to convert protein into a glucose unit; the ineffficiency shows up as heat.
In preserving the mitochondria function, could it be that slow-twitch muscle fiber having up to ten times more mitochondria per cell compared to fast-twitch fiber each one operating at lower RPM results in lower oxidative stress?

Peter said...

Intermittent, high intensity, short duration exercise would appear to increase your numbers of mitochondria then... Now where did I leave my pushbike when I got side tracked with my paving slabs?

supramaximal cycling

Peter

Paul said...

Good stuff. I'm not sure quite how this might fit in, but I have a colleague whose wife is Chinese and a biotech PhD. She was complaining about life in Utah, because neither of them seem to have had winter infections in several years since moving there. And she believes that occasionally getting a high temperature is good for health - it knocks out bacteria. (No idea if that was based in her biology background or is something from Chinese medicine),

Paul.

Peter said...

Hormesis, benefits of occasional stressors???? I've heard the benefits of some free radicals as an argument against mega dosing ascorbate.....

Me thinks most likely Chinese derivation, but non the less interesting for all that.

I'm just happy I missed the last two bugs out of nursery!

Peter

Stephan said...

Peter,

Thought you might be interested in this recent paper in Aging Cell. Apparently MnSOD levels regulate proliferation in mouse embryonic fibroblasts. It implies that mitochondrial ROS levels may affect cellular proliferation.

http://www.blackwell-synergy.com/doi/abs/10.1111/j.1474-9726.2008.00384.x

donny said...

Would living on a mountainside increase your slow twitch muscle, and therefor increase your mitochondrial population? A lot of the longevity myths involve mountains. Vilacamba, Hunza. Sixty minutes did a story years ago on a family in italy that seemed genetically immune to the dangers of a high-fat diet (lol), and they lived in a mountain village.
According to this article, "Way up high in Colorado, where tourists get nauseous, the locals live and keep on living - longer than virtually any other place in the United States.

A new Harvard University longevity study puts seven high-country Colorado counties in the top 10 in the nation, with an average lifespan of 81.3 years."

http://www.rockymountainnews.com/drmn/local/article/0,1299,DRMN_15_4985878,00.html

Peter said...

Hi donny,

There's a lot of epidemiology there, but maybe hills and cold.......... Sounds like Edinburgh to me!

Peter