Calorie restriction slows immune system aging

Chalk up one more point for calorie restriction (CR). Limiting the dietary intake of monkeys slows the age-related decline in the immune system. Specifically, CR delays the phenomenon known as T cell senescence, which is characterized by a slower rate of T cell production and a failure to maintain memory cells that have responded to past infections. From Messaoudi et al.:

Caloric restriction (CR) has long been known to increase median and maximal lifespans and to decreases mortality and morbidity in short-lived animal models, likely by altering fundamental biological processes that regulate aging and longevity. In rodents, CR was reported to delay the aging of the immune system (immune senescence), which is believed to be largely responsible for a dramatic increase in age-related susceptibility to infectious diseases. However, it is unclear whether CR can exert similar effects in long-lived organisms. Previous studies involving 2- to 4-year CR treatment of long-lived primates failed to find a CR effect or reported effects on the immune system opposite to those seen in CR-treated rodents. Here we show that long-term CR delays the adverse effects of aging on nonhuman primate T cells. CR effected a marked improvement in the maintenance and/or production of naïve T cells and the consequent preservation of T cell receptor repertoire diversity. Furthermore, CR also improved T cell function and reduced production of inflammatory cytokines by memory T cells. Our results provide evidence that CR can delay immune senescence in nonhuman primates, potentially contributing to an extended lifespan by reducing susceptibility to infectious disease.

It’s not clear whether one or several mechanisms are at work here. Levels of both naïve and memory T cells are increased under CR, both of which could be ascribed to an increase in cellular lifespan (i.e., a decrease in the rate of disappearance in both types of cells) without invoking a further increase in the rate of new T cell production.

But it seems that the cells are not merely more numerous but also more effective, able to mount more efficient specific immune responses without producing large quantities of sometimes counterproductive inflammatory cytokines. So the effect observed is not a simple matter of keeping cells around for longer.

These findings have significant clinical ramifications: Resistance to infection decreases over the lifespan, especially among the frail elderly (many of whom exhibit a dramatic increase in circulating levels of inflammatory cytokines, possibly originating in part from senescent memory T cells). Finding a means of boosting immune function in these individuals — e.g. by finding a CR mimetic compound that could trigger the T cell improvements observed in this primate study — could help turn decades of decrepitude and chronic illness into more robust “golden years” for millions of human beings.

Infection isn’t the only thing that specific immunity combats in the body. Cancers, whose cells often present unusual peptides on MHC as well as express inappropriate cell-surface proteins, is also detected and attacked by a combination of T and B cell action. Declining immune function represents another manner in which aging facilitates cancer.

Improving the maintenance and effectiveness of T cells by delaying senescence could therefore defend the body not only against infection, but also the ravages of late-life cancer. Hence, while CR isn’t all wine and roses, this is one more reason to study the phenomenon carefully in the search for clinical benefits.

(An excellent discussion of topics in immunological aging can be found at Fight Aging!)

(Hat tip to reader Attila of PImmBlog for sending in a link to this article.)

One comment

  1. The reason calorie restriction slows down aging is because it cuts off the food supply to Lyme and other parasitic infections. Also, the less we eat the more the immune system can focus on killing parasites and detoxifying, without the added burden of more food to assimilate.

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