I also speculated that resveratrol might make the muscles burn oxygen more efficiently, as opposed to increasing the blood's capacity to carry it or making the heart pump it more powerfully with each beat. It's like trying to measure the size of your car's gas tank (or how much the gas pump filled it with in one minute of pumping) by seeing how far it can go. If resveratrol gives us more or cleaner-burning mitochondria that do more work for a given amount of oxygen, that would also look to the test like they're getting more oxygen. Not that the exact mechanism matters, practically speaking.
Yes, I believe the mice tests (and human for that matter) show bigger mitochondria, more mitochondria, and more efficient mitochondria that spew out fewer free radicals and live longer. Feel free to correct me, anyone, if I'm wrong that they showed all these things. It is possible that some were theorized, but not proven.
Mice, yes. Men, not formally shown. No biopsies I am aware of. Sirtris may know.
This
study on caloric restriction and caloric restriction plus exercise in humans was the the one I was thinking of. There is so much overlap between caloric restriction and resveratrol, that it got filed away in the same folder in my brain.
It didn't show bigger mitochondria, but it did show more mitochondrial mass and more efficient mitochondria that also result in less DNA damage.
I vaguely remember reading that heart muscle cells were not given this mitochondrial boost -- that it was only the skeletal muscles. If so, then it would be mostly the receiving end that is making the difference, not the sending end (heart).
Worth looking up. Heart tissue is pretty tough to begin with, in terms of energy metabolism. However, Sirt7 activation prevents excessive collagen from forming in heart tissue, preventing heart enlargement in mice, and resveratrol activates Sirt7. So it is possible resveratrol use will prevent congestive heart failure ...
Circ Res. 2008 Mar 28;102(6):703-10. Epub 2008 Jan 31. Links
Sirt7 increases stress resistance of cardiomyocytes and prevents
apoptosis and inflammatory cardiomyopathy in mice.Vakhrusheva O,
Smolka C, Gajawada P, Kostin S, Boettger T, Kubin T, Braun T, Bober E.
Nice. I found this other
study on CR and resveratrol in mice.
...
Resveratrol in high doses has been shown to extend lifespan in some studies in invertebrates and to prevent early mortality in mice fed a high-fat diet. We fed mice from middle age (14-months) to old age (30-months) either a control diet, a low dose of resveratrol (4.9 mg kg(-1) day(-1)), or a calorie restricted (CR) diet and examined genome-wide transcriptional profiles. We report a striking transcriptional overlap of CR and resveratrol in heart, skeletal muscle and brain.
Both dietary interventions inhibit gene expression profiles associated with cardiac and skeletal muscle aging, and prevent age-related cardiac dysfunction. Dietary resveratrol also mimics the effects of CR in insulin mediated glucose uptake in muscle. Gene expression profiling suggests that both CR and resveratrol may retard some aspects of aging through alterations in chromatin structure and transcription. Resveratrol, at doses that can be readily achieved in humans, fulfills the definition of a dietary compound that mimics some aspects of CR.
...
I looked, but could not find where I saw that heart mitchondria density was not increased through resveratrol (or CR). I may have dreamed it up all by myself. Of course, I couldn't find any studies showing that it was increased in the heart either. Just studies stating overlap in gene expression in heart muscles by CR and resveratrol and general heart health.
Just pondering some of this... I wonder if some of the anti-cancer properties have anything to do with the number of mitochondria present in the cells? If there are more mitochondria, is there a greater chance of some of them "realizing" that the cell is damaged and that can initiate apoptosis? Or at a minimum, play a larger role in bringing the cell down than they otherwise would have, even if they aren't the initators?
Obviously, if they spew out fewer free radicals, then cancer might not start in the first place, but I'm just wondering if they help regulate it better when it does start if there are more of them?
Restoring mitochondrial function to cancer cells results in apoptosis, death of the cancer cell. It does seem logical that healthier mitochondria will prevent cancer from getting established in tissue.
Some Guru once explained to me that: Mitochondria deteriorate with age; when a cell divides, the healthy mitochondia are not distributed evenly in the daughter cells, and with age defective mitochondria are preferentially proliferated. With age, muscles become replete with cells whose mitochondria are non functioning or poorly functioning.
I just found this
study, discussing situations where mitochondrial density may *increase* aging.
...
Problems and paradigms
Mitochondria and ageing: winning and losing in the numbers game
AbstractMitochondrial dysfunction has long been considered a key mechanism in the ageing process but surprisingly little attention has been paid to the impact of mitochondrial number or density within cells. Recent reports suggest a positive association between mitochondrial density, energy homeostasis and longevity. However, mitochondrial number also determines the number of sites generating reactive oxygen species (ROS) and we suggest that the links between mitochondrial density and ageing are more complex, potentially acting in both directions. The idea that increased density, especially when combined with mitochondrial dysfunction, might accelerate ageing is supported by a negative correlation between mitochondrial density and maximum longevity in an interspecies comparison in mammals, and by evidence for an intimate interconnection between cellular ROS levels, mitochondrial density and cellular ageing. Recent data suggest that retrograde response, which activates mitochondrial biogenesis, accompanies cellular ageing processes.
We hypothesise that increased mitochondrial biogenesis, and possibly also impaired degradation and segregation of mitochondria, if occurring as adaptation to pre-existing mitochondrial dysfunction, might aggravate ROS production and thus actively contribute to ageing....
That seems to correlate with what the guru told you, if I am reading correctly?
Seems to me that we want to keep our mitochondria as healthy as possible to prevent this type of cascade and to prevent filling up the cell with dysfunctional mitochondria.
Another thing to ponder.... If we get a bunch of healthy mitochondria from resveratrol supplementation (or CR), what happens to those mitochondria if we remove the resveratrol? Do they continue being healthy, or do we risk them degrading to dsyfunctional mitochondria, thus effectively aging us?
Can we turn dysfunctional mitochondria into healthy mitochondria by adding resveratrol? Or will it simply cause the dysfunctional mitochondria to die off? And if they die off, will they take the cell with them?
I understand that mitochondria can increase in numbers in a cell, but I don't understand yet whether mitochondria can decrease in numbers, without taking the cell with them?
Have there been any studies on CR, where an animal was subjected to CR for the first half of life and then fed a normal diet for the rest of their life? If so, did they still live longer than those fed a regular diet their whole life, or did they live shorter lives?
Lastly, I wonder what benefits a *larger* mitochondria provides over a smaller one??
Larger mitochondria produce more energy.
Let me rephrase that. I wonder what benefits a larger mitochondrion provides over multiple, smaller ones that equal the mass of the larger one? Is there strength in numbers, or strength in being the 800 pound gorilla?
David
