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Siglec receptors impact mammalian lifespan by modulating oxidative stress.

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 - Elife (2015)

Bottom Line: In this study, we 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.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.Taken together, 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.

View Article: PubMed Central - PubMed

Affiliation: Glycobiology Research and Training Center, University of California, San Diego, San Diego, United States.

ABSTRACT
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 this study, we 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, we 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. 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. Taken together, 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.

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Data of 14 mammalian species used for analysis of correlation.Maximum lifespan and average adult body weight were retrieved from the AnAge database. The number of genes of each family was either found in the literature or searched following the methodology described in the ‘Materials and methods’.DOI:http://dx.doi.org/10.7554/eLife.06184.004
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fig1s1: Data of 14 mammalian species used for analysis of correlation.Maximum lifespan and average adult body weight were retrieved from the AnAge database. The number of genes of each family was either found in the literature or searched following the methodology described in the ‘Materials and methods’.DOI:http://dx.doi.org/10.7554/eLife.06184.004

Mentions: Numbers of CD33rSiglecs (A), KLK (B), IgG Fc receptors (C), and TLRs genes (D) and maximum lifespan in 14 mammalian species listed in Figure 1—figure supplement 1. (E and F) Correlation of CD33rSIGLECs and maximum lifespan after correction for average adult body weight and phylogeny. PGLS: λ = 1, phylogenetic tree I (E) or tree II (F) were used. The Pearson's correlation coefficient (R2) for each plot is indicated.


Siglec receptors impact mammalian lifespan by modulating oxidative stress.

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 - Elife (2015)

Data of 14 mammalian species used for analysis of correlation.Maximum lifespan and average adult body weight were retrieved from the AnAge database. The number of genes of each family was either found in the literature or searched following the methodology described in the ‘Materials and methods’.DOI:http://dx.doi.org/10.7554/eLife.06184.004
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4384638&req=5

fig1s1: Data of 14 mammalian species used for analysis of correlation.Maximum lifespan and average adult body weight were retrieved from the AnAge database. The number of genes of each family was either found in the literature or searched following the methodology described in the ‘Materials and methods’.DOI:http://dx.doi.org/10.7554/eLife.06184.004
Mentions: Numbers of CD33rSiglecs (A), KLK (B), IgG Fc receptors (C), and TLRs genes (D) and maximum lifespan in 14 mammalian species listed in Figure 1—figure supplement 1. (E and F) Correlation of CD33rSIGLECs and maximum lifespan after correction for average adult body weight and phylogeny. PGLS: λ = 1, phylogenetic tree I (E) or tree II (F) were used. The Pearson's correlation coefficient (R2) for each plot is indicated.

Bottom Line: In this study, we 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.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.Taken together, 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.

View Article: PubMed Central - PubMed

Affiliation: Glycobiology Research and Training Center, University of California, San Diego, San Diego, United States.

ABSTRACT
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 this study, we 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, we 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. 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. Taken together, 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.

Show MeSH
Related in: MedlinePlus