Research Article: Physical decline and survival in the elderly are affected by the genetic variability of amino acid transporter genes

Date Published: April 18, 2018

Publisher: Impact Journals

Author(s): Paolina Crocco, Eneida Hoxha, Serena Dato, Francesco De Rango, Alberto Montesanto, Giuseppina Rose, Giuseppe Passarino.

http://doi.org/10.18632/aging.101420

Abstract

Amino acid (AA) availability is a rate-limiting factor in the regulation of muscle protein metabolism and, consequently, a risk factor for age-related decline in muscle performance. AA transporters are emerging as sensors of AA availability and activators of mTORC1 signalling, acting as transceptors. Here, we evaluated the association of 58 single nucleotide polymorphisms (SNPs) in 10 selected AA transporter genes with parameters of physical performance (Hand Grip, Activity of Daily Living, Walking time). By analysing a sample of 475 subjects aged 50-89 years, we found significant associations with SLC7A5/LAT1, SLC7A8/LAT2, SLC36A1/PAT1, SLC38A2/SNAT2, SLC3A2/CD98, SLC38A7/SNAT7 genes. Further investigation of the SNPs in a cross-sectional study including 290 subjects aged 90-107 years revealed associations of SLC3A2/CD98, SLC38A2/SNAT2, SLC38A3/SNAT3, SLC38A9/SNAT9 variability with longevity. Finally, a longitudinal study examining the survival rate over 10 years showed age-dependent complexity due to possible antagonistic pleiotropic effects for a SNP in SLC38A9/SNAT9, conferring a survival advantage before 90 years of age and a disadvantage later, probably due to the remodelling of AA metabolism. On the whole, our findings support the hypothesis that AA transporters may impact on the age-related physical decline and survival at old age in a complex way, likely through a mechanism involving mTORC1 signalling.

Partial Text

One of the most dramatic modifications associated with human aging is the progressive decline in skeletal muscle mass and function, known as sarcopenia. Sarcopenia causes physical function impairment, leading to a loss of functional independence and to an increased incidence of adverse health outcomes [1,2]. The prevalence of this condition, which is progressively increasing due to the prolonged life expectancy, has led in the recent decades to increased needs for health care services and resources to support older people [3]. The rate of skeletal muscle loss is estimated at 8% per decade from the 4th until 7th decade, with about 15% lost each decade after 70 years of age and loss of strength is estimated to be even longer [4].

Demographic, clinical, and anthropometric characteristics of the analysed sample are presented in Table 1. Among the selected SNPs, 10 did not pass the QC phase. In particular, four SNPs were excluded due to a MAF (Minor Allele Frequency) lower than ten percent per locus (rs17112008, rs7968173, rs1175, rs7735053), while six were excluded because they showed a significant deviation from HWE in control subjects (rs11749532, rs7736177, rs2897968, rs17794251, rs7193392, rs8058969).

The goal of the current study was to investigate the impact of SNPs in selected AA transporters genes on physical performance and survival at old age.

 

Source:

http://doi.org/10.18632/aging.101420

 

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