TFAM, Aging, and Calorie Restriction

In recent years, researchers have shown that introducing additional mitochondrial transcription factor A (TFAM) can reverse some age-related loss of mitochondrial function. Research on mitochondrial protofection seems to have been sidetracked by this finding also - the researchers were using TFAM as a part of a means to replace damaged mitochondrial DNA, but are now more focused on TFAM itself, arguably a less useful path forward.

In this research, scientists show that TFAM levels differ in old and young rats, and life-long calorie restriction eliminates that difference. Calorie restriction slows aging and improves near every measure of metabolism examined to date, so we should expect to see it reduce any given difference between old and young tissues. As for many lines of research, this points to the importance of mitochondria in aging:

Aging affects mitochondria in a tissue-specific manner. Calorie restriction (CR) is, so far, the only intervention able to delay or prevent the onset of several age-related changes also in mitochondria. Using livers from middle age (18-month-old), 28-month-old and 32-month-old ad libitum-fed and 28-month-old calorie-restricted rats we found an age-related decrease in mitochondrial DNA (mtDNA) content and mitochondrial transcription factor A (TFAM) amount, fully prevented by CR. We revealed also an age-related decrease, completely prevented by CR, for the proteins PGC-1α, NRF-1 and cytochrome c oxidase subunit IV, supporting the efficiency of CR to forestall the age-related decrease in mitochondrial biogenesis. Furthermore, CR counteracted the age-related increase in oxidative damage to proteins, represented by the increased amount of oxidized peroxiredoxins in the ad libitum-fed animals.

To investigate further the age- and CR-related effects on mitochondrial biogenesis we analyzed the in vivo binding of TFAM to specific mtDNA regions and demonstrated a marked increase in the TFAM-bound amounts of mtDNA at both origins of replication with aging, fully prevented by CR. A novel, positive correlation between the paired amounts of TFAM-bound mtDNA at these sub-regions was found in the joined middle age ad libitum-fed and 28-month-old calorie-restricted groups, but not in the 28-month-old ad libitum-fed counterpart suggesting a quite different modulation of TFAM binding at both origins of replication in aging and CR.

Considering all together the present results, we demonstrate in rat liver a very articulated age-related decrease in mitochondrial biogenesis leading to the loss of mtDNA probably also through the increase of TFAM binding to both origins of replication. [This] gives an interesting and novel clue to evaluate the preservation of mitochondrial biogenesis as very relevant in the anti-aging action of CR. Of course, future work will be necessary to further verify such hypothesis also in consideration of the therapeutic applications that might lead, through up-regulation of PGC-1α expression and maintenance of mtDNA, to a longer-lasting mitochondrial functionality.

Link: http://dx.doi.org/10.1371/journal.pone.0074644

Comments

Reason,

There was a South American man recently in the news that was reported to be 123 years old. It seems that a combination of factors influenced his longevity:

A) Genetics (I do not know this specifically, but being that old I think it is fair to say that his genes at least helped him out a little bit)

B) Exercise (He claims he was in the army when younger, and says he has made a habit of walking - for how long the article does not say, plus his memory sounded slightly erratic in the interview)

C) Minimal meat consumption (He is from an almost "favella" like area where excessive meat availability was not an option; also, said he consumed a lot of potatoes that would filling to this individual in the absence of meat consumption running parallel to his presence of modest exercise)

D) Calorie Restriction (Coca leaf chewing is a prominent recorded practice amongst many people in South America - he also admitted it in the interview)

So, my question is this. I am 21 now and have been focusing on a daily regiment of 10-30 minute exercise regiment per, day 7 days a week: the 10 minute intervals would be only jogging if I am short on time and/or want to build up endurance, but the 30 minute would at minimum a "power walk." Sometimes I do a combination of walking/jogging.

I am trying to also start a caloric restriction diet now but am having a hard time balancing the exercising with the dieting. Obviously, vigorous exercise promotes my hunger but I have now come to a weekly habit of running these two aspects of my life in an inconsistent manner. For example, one day I will practice exercise but not the caloric restriction, and another day I will successfully do the caloric restriction but not the exercise.

Can you provide insight on to whether this is the best approach? Should I focus on one at a time indefinitely and/or see if I can tackle both later on when I have had more experience with one? I have been doing the exercise since I turned 21 and have been serious with both exercise and CR for the last 1 month or so... I am in college now, as well as in a comfortable position to worry about this now than later when I begin my career...

Posted by: Donald at September 24th, 2013 5:49 PM

@Donald: The South American man is very definitely not the real thing. There's a lot of exaggeration going on, and the media credulously reports it as the truth. Any claims of age should be treated with skepticism until validated by organizations like the Gerontology Research Group.

It's perfectly possibly to practice moderate regular exercise (30 minutes a day, or 150 minutes a week, or similar) and calorie restriction concurrently.

There's little evidence that more exercise than that is very beneficial in humans, but plenty of evidence for the big difference between being sedentary and engaging in moderate regular exercise. The people who do undertake much more exercise than that and are studied are usually athletes, and it's hard to tell whether they live longer because of more exercise, or because they are more robust than the average fellow, which is why they are more likely to be athletes.

But of course you should do you own reading around the research and arrive at something that you think works for you.

Posted by: Reason at September 24th, 2013 6:10 PM

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