title: Association of Klotho polymorphisms with healthy aging: a systematic review and meta-analysis.
abstract: Today it is clearly evident that genetic background constitutes an integral part of aging and longevity. Many studies on long-lived people have been conducted emphasizing the role of certain genes in long life. Classic case-control studies, genome-wide association studies, and high-throughput sequencing have permitted identification of a variety of genetic variants seemingly associated with longevity. Over the years, aging research has focused on the insulin/insulin-like growth factor-1 (IGF-1) signaling pathway because of its evolutionarily conserved correlation with life-span extension in model animals. Indeed, many single-nucleotide polymorphisms (SNPs) associated with longevity were identified in genes encoding proteins that take part in this metabolic pathway. Closely related to this pathway is the Klotho gene. It encodes a type-I membrane protein expressed in two forms, membrane and secreted. The latter form suppresses oxidative stress and growth factor signaling and regulates ion channels and transporters. In particular, its over-expression seems to be able to suppress insulin/IGF-1 signaling extending life span. Thus, our aim was to assemble the results in the literature concerning the association between the functional variant of the Klotho "KL-VS" stretch, which contains six polymorphisms in linkage disequilibrium, and successful aging to quantify the possible effect of the variants. The results of our systematic review indicate that the Klotho KL-VS variant is associated with healthy aging.
authors.affiliation: 1 Immunosenescence Unit, Department of Pathobiology and Medical and Forensic Biotechnologies, University Hospital, University of Palermo , Palermo, Italy .
authors.forename: Danilo
authors.initials: D
authors.lastname: Di Bona
authors.forename: Giulia
authors.initials: G
authors.lastname: Accardi
authors.forename: Claudia
authors.initials: C
authors.lastname: Virruso
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Candore
authors.forename: Calogero
authors.initials: C
authors.lastname: Caruso
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005966:Glucuronidase / Q000235:genetics*; D006262:Health; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D000090265:Klotho Proteins; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D055815:Young Adult
chemical_list: D005966:Glucuronidase; D000090265:Klotho Proteins