What I didn’t do over my Thanksgiving vacation

Like most Americans (and anyone else lucky enough to be residing in the US over the Thanksgiving holiday), the farthest thing from my mind this past Thursday (and Friday, and Saturday, and Sunday) was limiting my caloric intake.

Quite to the contrary, my countryfolk and I pushed the envelope of ad libitum consumption. If there’s any good news from the field of biogerontology that’s relevant to the past weekend, it’s the recent findings that a red wine-derived compound rescues the health of mice eating a high-calorie diet. (Let’s hope it works in humans; sign this lab rat up for the study. High doses required? It’s a sacrifice I’m willing to make…for science.)

But now it’s back to work, and for biogerontologists that includes cataloging and understanding the ways in which life-extending regimens like calorie restriction change gene expression. From Fu et al., a cross-organ microarray study:

Aging alters the expression of a variety of genes. Calorie restriction (CR), which extends life span in laboratory rodents, also changes gene expression. This study investigated changes in gene expression across three different tissues from the same mouse to examine how aging and early stage CR influence gene expression in different tissues of an organism. Expression profiling of heart, liver, and hypothalamus tissues was done in young (4–6 months) ad libitum fed (AL), young CR (2.5–4.5 months of CR), and old (26–28 months) AL male C57BL/6 mice. Aging significantly altered the expressions of 309, 1819, and 1085 genes in heart, liver, and hypothalamus tissues, respectively. In nine genes, aging altered expression across all three tissues although the regulation directions did not agree across all three tissues for some genes. Early stage CR in young mice significantly changed the expressions of 192, 839, and 100 genes in heart, liver, and hypothalamus tissues, respectively, and seven genes altered expression across all three tissues; three were up regulated and four were down regulated. The results of Gene Ontology (GO) Biological Process analysis indicated up regulation of antigen processing/presentation genes by aging and down regulation of stress response genes by early stage CR in all three tissues. The comparison of the results of aging and short term CR studies showed there were 389 genes, 18 GO biological processes, and 20 GO molecular functions in common.

I was surprised that stress response genes were downregulated by early-stage CR, since one of my favorite theories to explain the life extension value of CR involves hormesis — the idea that exposing oneself to low-grade stress (like fasting, which does induce a stress response) will protect the body against high-grade stress it encounters later on, a sort of molecular was nicht umbringt macht stärker.

But Fu et al. see quite the opposite, an overall downregulation of the stress response early in CR. The clearest interpretation is that CR isn’t protective in a hormetic way, but rather extends life via another mechanism. One wonders if the upregulation of antigen presentation that they observe could be involved in improved immune surveillance and removal of transformed or senescent cells over the lifespan.

Regardless, I’m thankful for their work.