Grant: Operating Grant

We are studying a strain of mouse mutants (Mclk1+/-) that live longer than normal mice. We have found that when we compare aged mutants to normal mice of the same age, the mutants appear physiologically younger, that is, they are healthier and more youthful. We have also found that these mutants have a stronger than normal immune reactivity against infectious agents, which seems to allow them to recover more completely from infection. Finally, we have found that these mutants might live longer than normal mice only under conditions that are not completely aseptic, as if their enhanced longevity was mostly due to their more efficient immune system. Our hypothesis is that sustaining infections throughout life, repeatedly or chronically, participates in creating the damage to tissues and organs that is central to aging. In the project that we are proposing we seek to test this hypothesis and to understand in detail the biological mechanisms that allow Mclk1+/- mice to have a particularly robust immune system. Understanding these mechanisms might allow us to learn how to strengthen the immune system of people as well.