Update on the PAPP-A Longevity Mutation
You'll recall that mice with the PAPP-A gene deleted live 30% longer in good health than their fellows. Following up, researchers are eliminating possibilities in the search for the mechanism of action: "We determined whether 18-month-old PAPP-A knock-out (KO) mice compared to their wild-type [WT] littermates have reduced energy expenditure and/or altered glucose-insulin sensitivity. Food intake, and total energy expenditure and resting energy expenditure as measured by calorimetry, were not different between PAPP-A KO and WT mice ... However, there was an increase in spontaneous physical activity in PAPP-A KO mice. Both WT and PAPP-A KO mice exhibited mild insulin resistance with age, as assessed by fasting glucose/insulin ratios. Oral glucose tolerance and insulin sensitivity were not significantly different between the two groups of mice ... Thus, neither reduced 'rate of living' nor altered glucose-insulin homeostasis can be considered key determinants of the enhanced longevity of PAPP-A KO mice." We'll be hearing more on this topic in the years ahead, I'm sure - more healthy life with no downside through a simple genetic manipulation is an attractive idea.