Fight Aging!

Aging science blog Ouroboros recently roused from its slumber for an excellent series of posts covering the Bay Area Aging Meeting held earlier this month. This is a well attended gathering of biogerontologists, who are fairly numerous in that part of the world. There are a number of important laboratories in California, such as the Kenyon Lab at UCSF and the Buck Institute for Age Research, which leads to a fair turnout at most local life science events.

Here is the coverage by session, one post for each set of presentations, with some of the highlights singled out and quoted below:

Bay Area Aging Meeting: Session I

Cognitive decline occurs with age: speed of processing, working memory, and long-term memory all decline. Presumably cell loss is partially to blame - not only loss of neurons, but also other types of cells (e.g., oligodendrocytes). Neural stem cells (NSC) can regenerate lost cells to some extent, but their ability to do so diminishes with age.

The Brunet lab is looking at the idea that pathways that control lifespan in "lower" organisms (worms; yeast) may be involved in regenerative capacity in "higher" organisms (us; mice). Rafalski's work is focusing on the now-famous SIRT1. SIRT1 is downregulated over the course of differentiation, so there's a smoking gun - but is there a causative relationship between SIRT1 downregulation and loss of regenerative capacity in NSCs?

Bay Area Aging Meeting: Session II

Furman looked at the response of 85 individual human subjects to vaccination, making a wide range of measurements (antibody titer, cytokine levels, gene expression), with the goal of creating a classifier system that can be used to predict the efficacy of the immune response. Young people tend to respond to antigens very similarly to one another (i.e., efficiently), whereas elderly subjects were split into two categories: cytokine responders and non-responders. These categories correlated with expression of genes associated with longevity, suggesting that immunosenescence and longevity represent two sides of the same coin.

Bay Area Aging Meeting: Session III

Regulatory T cells (Treg) maintain immune tolerance, i.e., they stop the rest of the immune system from attacking the body. They accomplish this by suppressing differentiation of naive cells and the activation of effector cells. This, in turn, helps to prevent autoimmune disease and graft rejection. However, Treg cells increase their activity during aging, which might make elderly people more susceptible to infection.

Treg activity is regulated by FoxP3, which is in turn modified by acetylation that is regulated by SIRT1. ... In questions, I asked whether SIRT1 inhibition could therefore be used to prevent autoimmune disease - the short answer is "yes"

Bay Area Aging Meeting: Session IV

If aging is an engineering problem, then we should be able to solve the engineering challenges more easily in simple systems. By introducing genes from a long-lived organism into the genome of a short-lived organism, it should be possible to add pro-longevity functions - in effect "upgrading" the short-lived animal so that it lives longer. Sagi has set out to do just that, by transferring genes from the long-lived zebrafish (4-year lifespan) to the short-lived worm (4-week lifespan).

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The next obvious question: Can "upgrade" genes be combined to further increase lifespan? Indeed they can: several pairwise combinations of genes combined to extend lifespan longer than either single gene alone. At some point it worked a little too well: the lifespan of the worms started getting long enough that the survival curves became unwieldy.

Evolution doesn't select for longevity - a fact amply demonstrated by how many different minor changes in metabolism can make worms, flies, and mice live longer in good health.