A Little Calorie Restriction Research

A couple of calorie restriction research papers caught my eye today, and I thought I'd share. First out of the gate is a study of one of a number of gene products associated with and necessary for the benefits of calorie restriction, but whose mechanisms are still poorly understood:

NQR1 controls lifespan by regulating the promotion of respiratory metabolism in yeast

The activity and expression of plasma membrane NADH coenzyme Q reductase is increased by calorie restriction (CR) in rodents. Although this effect is well established and is necessary for CR's ability to delay aging, the mechanism is unknown.

Here we show that the Saccharomyces cerevisiae homolog, NQR1, resides at the plasma membrane and when overexpressed extends both replicative and chronological lifespan. We show that NQR1 extends replicative lifespan in a SIR2-dependent manner by shifting cells towards respiratory metabolism. Chronological lifespan extension, in contrast, occurs via a SIR2-independent decrease in ethanol production. We conclude that NQR1 is a key mediator of lifespan extension by CR through its effects on yeast metabolism.

The function of SIR2 in yeast is basically the same as SIRT1 in mammals, so it's probably the case that we can learn about the function of plasma membrane NADH coenzyme Q reductase in mammals by looking at NQR1 in yeast. As things move forward in the investigation of metabolism and calorie restriction, I wouldn't be surprised to see many different (possibly interacting) mechanisms that lead to essentially the same result, where cells are pushed towards greater levels of efficiency and recycling of damage.

But onwards to look at another study that provides confirmation of benefits resulting from the practice of calorie restriction.

The molecular architecture of myelinated peripheral nerves is supported by calorie restriction with aging

Peripheral nerves from aged animals exhibit features of degeneration, including marked fiber loss, morphological irregularities in myelinated axons and notable reduction in the expression of myelin proteins.

...

While calorie restriction (CR) is known to slow the aging process in the central nervous system, its influence on peripheral nerves has not been investigated in detail. To determine if dietary restriction is beneficial for peripheral nerve health and glial function, we studied sciatic nerves from rats of four distinct ages (8-, 18-, 29- and 38-months) kept on an ad libitum (AL) or a 40% CR diet.

Age-associated reduction in the expression of the major myelin proteins and widening of the nodes of Ranvier are attenuated by the dietary intervention

...

The improvements in nerve architecture with diet restriction, in part, are underlined by sustained expression of protein chaperones and markers of the autophagy-lysosomal pathway. Together, the in vitro and in vivo results suggest that there might be an age-limit by which dietary intervention needs to be initiated to elicit a beneficial response on peripheral nerve health.

The part about chaperones and autophagy refers to increased signs of cleanup of damaged cellular components taking place - which is thought to be one important way in which calorie restriction extends life. If you have less damage hanging around, on average, that damage will cause fewer additional problems. In this case it means nerves work better for longer.

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