Role of Inflammation in Lifespan

Mammalian species with greater copy numbers of anti-inflammatory genes have longer maximum lifespans.

A major contributor in the process of aging is lifelong accumulation of molecular damage resultant from inflammation and free radical damage.  In that the CD33rSiglec family of proteins are known to help protect our cells from becoming inflammatory collateral damage, a team from the University of California/San Diego School of Medicine (California, USA) investigated the role of CD33rSiglecs in lifespan extension.   The CD33rSIGLEC genes encode siglec receptors that bind sialic acids -- sugar molecules found on many cells. These siglec receptors stick out like antennae on the outer surface of immune cells, probing the surface of other "self" cells in the body. When sialic acids bind siglec receptors, they transmit the message to the inside of the cell. This signal relay puts a brake on immune cell activation. In this way, the CD33rSiglec receptors help dampen chronic inflammation and reactive oxygen species in the body.  Ajit Varki and colleagues report a correlation between CD33rSIGLEC gene copy number and maximum lifespan across 14 mammalian species. In addition, they found that mice lacking one CD33rSIGLEC gene copy don't live as long as normal mice, have higher levels of reactive oxygen species and experience more molecular damage. Observing that: “Removal of Siglec-E causes the development of exaggerated signs of aging at the molecular, structural, and cognitive level. We found that accelerated aging was related both to an unbalanced ROS metabolism, and to a secondary impairment in detoxification of reactive molecules, ultimately leading to increased damage to cellular DNA, proteins, and lipids,: the study authors submit that: “our data suggest that CD33rSiglecs co-evolved in mammals to achieve a better management of oxidative stress during inflammation, which in turn reduces molecular damage and extends lifespan.”

Schwarz F, Pearce OM, Wang X, Samraj AN, Läubli H, Garcia JO, Lin H, Fu X, Garcia-Bingman A, Secrest P, Romanoski CE, Heyser C, Glass CK, Hazen SL, Varki N, Varki A, Gagneux P. “Siglec receptors impact mammalian lifespan by modulating oxidative stress.”  Elife. 2015 Apr 7;4.