Accepted Manuscript

Title: Metabolism and successful aging: polymorphic variation of syndecan-4 (SDC4) gene associate with longevity and lipid profile in healthy elderly Italian subjects.

Author: Giuseppina Rose Paolina Crocco Francesco De Rango Andrea Corsonello Fabrizia Lattanzio Maria De Luca Giuseppe Passarino

Mechanisms of Ageing and Development

Please cite this article as: Rose, Giuseppina, Crocco, Paolina, Rango, Francesco De, Corsonello, Andrea, Lattanzio, Fabrizia, Luca, Maria De, Passarino, Giuseppe, Metabolism and successful aging: polymorphic variation of syndecan-4 (SDC4) gene associate with longevity and lipid profile in healthy elderly Italian subjects.Mechanisms of Ageing and Development http://dx.doi.org/10.1016/j.mad.2015.08.003

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Metabolism and successful aging: polymorphic variation of syndecan-4 (SDC4) gene

Rose1*, Paolina Crocco1*, Francesco De Rango1, Andrea Corsonello3, Fabrizia

Maria De Luca2, Giuseppe Passarino1.

3Italian National Research Centre on Ageing, Cosenza, Italy

4Scientific Direction of the Italian National Research Centre on Ageing, Ancona,

*Giuseppina Rose and Paolina Crocco equally contributed to this study.

Corresponding Author:

SDC

links longevity and lipid profile.  SDC

variants rs

and rs

in SDC

are associated with human  SDC

variants rs

and rs

in SDC

have an effect on the lipid profile

ABSTRACT

SDC4 alleles affect lipid profile in elderly subjects and may in part mediate the link between

Keywords

Aging; Longevity; Extracellular Matrix; Metabolism; Syndecans

adhesion and behavior (Morgan et al., 2007; Xianet al., 2010).

that signaling between cells and the ECM plays a pivotal role in tissue/organ homeostasis

Sdc mutant flies also display less fat and glycogen reserves and lower metabolic activity than

invertebrates, humans contain four SDC genes. Three of them, SDC1, SDC2, and

(aged 64-107). We then determined whether the SNPs found to be associated with old

2. METHODS

2.1. Study subjects

The study was carried out in a cohort of 624 unrelated subjects (287 males and 337 females, age

of Calabria, Italy. A written informed consent was obtained from all participants before enrolling

in the study.

2.2. Phenotypic measurements

HbA1c was chosen as a clinical marker of CHD because levels of HbA1c between 6.0 and

clothes and without shoes. Blood samples were withdrawn after 12-h overnight fast and

analysis. The selected SNPs are reported in Table

and a primer extension reaction using the mass extension primer and the terminator. The

95%; however, genotyping completion rate was lower than 65% for rs6104125.

model]). For each model, a z-score was returned, representing the z-statistics for the

analyses, with a pmodel referred to the p value for the most likely genetic model.

SNPs influenced gene expression, we explored the Genotype-Tissue Expression (GTEx)



3.1. SCD4 association with longevity

longevity, however, was not significant after adjusting for multiple testing (Table 2); hence,

caution is needed in interpreting this finding. The z-statistics of these models indicated that

rs2228384. The haplotype analysis for these two polymorphic sitesrevealed that, although the

Thus, haplotype analysis confirmed association results with the single markers.

with longevity, was correlated with higher levels of LDL-C (positive score; (cid:1868)Recessive Model = 0.022).

3.2. Exploring the functional consequences of SDC4 variants

“likely to affect binding” (score 2b).

of these markers may be the actual causal variant.

4. DISCUSSION

the SDC4 gene affect human longevity. Specifically, we found that Italian elderly subjects

particularly intriguing since we previously showed that American children (age 7 to 12

disease (Miller et al., 2011), suggests that this SDC4 genetic variant might

molecular link between SDC4 and lipid profile.

strongly motivate further studies to determine how SDC4 genotypes can affect human health

Conflict of interest

ACKNOWLEDGEMENT

This work was supported by the European Union's FP7 [grant number 259679] and by

di molecole di interesse per la salute dell'uomo".

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