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

• SDC4 links longevity and lipid profile.
• SDC4 variants rs1981429 and rs2251252 in SDC4 are associated with human longevity.
• SDC4 variants rs1981429 and rs2251252 in SDC4 have an effect on the lipid profile in elderly subjects.

Evidences from model systems and humans have suggested that genetic alterations in cell–ECM interactions and matrix-mediated cellular signaling cascades impact different aspects of metabolism and thereby life span. In this frame, a genetic variant (rs1981429) in the SDC4 gene encoding for syndecan-4, a central mediator of cell adhesion, has been associated with body composition in children and coronary artery disease in middle-age subjects. In order to test the hypothesis that syndecans might affect life span by affecting metabolic endophenotypes, 11 SNPs within the SDC4 gene were tested for association with longevity in a cohort of 64–107 aged individuals. We then determined whether the longevity-associated SNPs were correlated with metabolic parameters in the age group 64–85 years. RobustSNP association tests showed that rs1981429 was negatively associated with longevity (Theop = 0.028), but also with high levels of triglyceride (Theop = 0.028) and low levels of low-density lipoprotein-cholesterol (LDL-C) (Theop = 0.009). On the other hand, rs2251252 was found to be positively correlated with longevity (Theop = 0.018) and high LDL-C (Theop = 0.022). On the whole, our results suggest that SDC4 alleles affect lipid profile in elderly subjects and may in part mediate the link between LDL-C and longevity.