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Modern biotechnology is capable of churning out information somewhat faster than the research community can presently make sense of it. Like armor and weapons, the technologies of organization, synthesis and management seem to be perpetually a generation behind the technologies of investigation and exploration. Along those lines, it's easier to run an experiment than to write a really good theory - but there's no shortage of theories when it comes to aging. Now that the biochemistry of metabolism as it pertains to aging is becoming clearer, the related theories are becoming more detailed, specific, localized and provable. This is a good thing.
Energy metabolism, altered proteins, sirtuins and ageing: converging mechanisms?
The predominant molecular symptom of ageing is the accumulation of altered gene products. Nutritional studies show that ageing in animals can be significantly influenced by dietary restriction. Genetics has revealed that ageing may be controlled by changes in intracellular NAD/NADH ratio regulating sirtuin activity. Physiological and other approaches indicate that mitochondria may also regulate ageing. A mechanism is proposed which links diet, exercise and mitochondria-dependent changes in NAD/NADH ratio to intracellular generation of altered proteins.
It is suggested that ad libitum feeding conditions decrease NAD availability which also decreases metabolism of the triose phosphate glycolytic intermediates [which] can spontaneously decompose into methylglyoxal (MG).
MG is a highly toxic glycating agent and a major source of protein advanced-glycosylation end-products (AGEs). MG and AGEs can induce mitochondrial dysfunction and formation of reactive oxygen species (ROS), as well as affect gene expression and intracellular signalling. In dietary restriction-induced fasting, NADH would be oxidised and NAD regenerated via mitochondrial action. This would not only activate sirtuins and extend lifespan but also suppress MG formation. This proposal can also explain the apparent paradox whereby increased aerobic activity suppresses formation of glycoxidized proteins and extends lifespan. Variation in mitochondrial DNA composition and consequent mutation rate, arising from dietary-controlled differences in DNA precursor ratios, could also contribute to tissue differences in age-related mitochondrial dysfunction.
You'll actually find most of what you need to know to understand the scientese above by reading up on introductions to calorie restriction, the contribution of mitochondrial damage to aging, and AGEs - it's nowhere near as complex a set of ideas as it might at first appear:
It is gratifying to see attempts to tie many threads of aging research together into one synthesis, and to see that synthesis be testable at many easy, specific points. That's a sign of progress.
Posted by Reason at October 15, 2007 8:24 PM
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