Aging is a multifactorial process that includes the lifelong accumulation of molecular damage, leading to age-related frailty, disability and disease, and eventually death. In a study called, “Siglec receptors impact mammalian lifespan by modulating oxidative stress” on elifesciences.org, researchers from University of California, San Diego and Cleveland Clinic Lerner Research Institute examine how oxidative stress effects lifespan.
In the study, authors Schwarz, Pearce et al report evidence of a significant correlation between the number of genes encoding the immunomodulatory CD33-related sialic acid-binding immunoglobulin-like receptors (CD33rSiglecs) and maximum lifespan in mammals. In keeping with this, they show that mice lacking Siglec-E, the main member of the CD33rSiglec family, exhibit reduced survival. Removal of Siglec-E causes the development of exaggerated signs of aging at the molecular, structural, and cognitive level. They found that accelerated aging was related both to an unbalanced ROS (Reactive oxygen species – chemically reactive molecules containing oxygen) metabolism, and to a secondary impairment in detoxification of reactive molecules, ultimately leading to increased damage to cellular DNA, proteins, and lipids. Taken together, their 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.
These data indicate that the number of CD33rSIGLEC genes correlates to lifespan in mammals. This correlation appears independent from phylogenetic constraints, from effects of genomic location, from a generally observed rapid evolution of receptors involved in immune responses and from body mass.
The researchers used a mouse model to seek experimental evidence for the observed correlation, as mice have a simplified CD33rSiglec profile compared to other mammalian model systems, in terms of number of genes and expression patterns. Results indicated that elimination of Siglec-E leads to accelerated oxidative modification of DNA, proteins and lipids at the systemic level, via elevated ROS and reactive nitrogen species (RNS) production – resulting in a faster progression of aging and, consequently, to increased frailty leading to an earlier death.
The findings of the study also support the concept that alteration of the ROS homeostasis accelerates aging. Access the full study here: http://elifesciences.org/content/4/e06184
