Researchers are uncovering longevity mutations in mice fairly rapidly these days. The cost of genetic engineering is falling, the concept of extending longevity through altering the processes of metabolism is well established, and so much more experimentation is taking place than in past years. Here is another recent example from the open access PLoS ONE, this time with the unusual twist that it seems to work only for male mice:
Mutations that cause a reduction in protein kinase A (PKA) activity have been shown to extend lifespan in yeast. Loss of function of mammalian RIIβ, a regulatory subunit of PKA expressed in brain and adipose tissue, results in mice that are lean and insulin sensitive. It was therefore hypothesized that RIIB null (RIIβ−/−) mice would express anti-aging phenotypes.
We conducted lifespan studies using 40 mutant and 40 wild type (WT) littermates of equal gender numbers and found that both the median and maximum lifespans were significantly increased in mutant males compared to WT littermates. The median lifespan was increased from 884 days to 1005 days [and] the 80% lifespan (defined here as 80% deaths) was increased from 941 days to 1073 days. [There] was no difference in either median or 80% lifespan in female genotypes.
Protein kinase A is related, via variants of adenosine monophosphate (AMP), to the mitochondrial biochemistry that produces the fuel biochemical ATP. A lot of important metabolic signaling and regulation centers around the processing of food into energy, and altering it can change life span in either direction. See the research into calorie restriction or insulin pathways for two areas of present intense scientific interest.
The effects of altering metabolic regulation are not always clear, given the many possible confounding factors. Why does life span increase or decrease in any given case? Is it a primary effect, or resulting from something secondary to the genetic change? For example, the researchers here suggest that the PKA life extension results from males having less body fat:
Although the mechanisms for the extended lifespan are not yet known, the fact that it is observed only in males provides a uinique paradigm for further investigation of this interesting gene pathway. In this regard, we show preliminary evidence to suggest that the lifespan phenotype seen in the absence of RIIβ is directly associated with decreased body fat but not insulin sensitivity.
This seems reasonable on the face of it. As you may recall, other researchers have demonstrated that you can increase mouse life span by removing visceral fat. The benefits to longevity were somewhat less than those produced by calorie restriction, but still significant. Excess fat tissue is linked to age-related disease and degeneration, increased chronic inflammation, and various other woes. It's not something you'd want to keep.
Enns, L., Morton, J., Treuting, P., Emond, M., Wolf, N., McKnight, G., Rabinovitch, P., & Ladiges, W. (2009). Disruption of Protein Kinase A in Mice Enhances Healthy Aging PLoS ONE, 4 (6) DOI: 10.1371/journal.pone.0005963