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Physical decline and survival in the elderly are affected by the genetic variability of amino acid transporter genes
- Source :
- Aging (Albany NY)
- Publication Year :
- 2018
-
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.
- Subjects :
- 0301 basic medicine
Male
medicine.medical_specialty
Amino Acid Transport Systems
Genotype
ADL
media_common.quotation_subject
Longevity
Single-nucleotide polymorphism
Biology
Polymorphism, Single Nucleotide
sarcopenia
Hand grip
03 medical and health sciences
0302 clinical medicine
Internal medicine
Activities of Daily Living
medicine
SNP
Humans
Amino acid transporter
Genetic variability
Longitudinal Studies
Survival rate
Gene
mTORC1
media_common
Aged
Aged, 80 and over
muscle decline
Hand Strength
aging
Cell Biology
Middle Aged
medicine.disease
Survival Analysis
amino acid transporter genes
030104 developmental biology
Endocrinology
Cross-Sectional Studies
Sarcopenia
Female
030217 neurology & neurosurgery
Research Paper
Subjects
Details
- ISSN :
- 19454589
- Volume :
- 10
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Aging
- Accession number :
- edsair.doi.dedup.....eca9d1f0fefa5c6d2580d53a491023d5