# Resistance training partially restores age-related differences in skeletal muscle amino acid transporters - secondary analysis from two randomized controlled trials

**Authors:** E. Lander, H. Hamarsland, M.J. Lees, D. Moore, T. Raastad

PMC · DOI: 10.1016/j.jnha.2026.100808 · The Journal of Nutrition, Health & Aging · 2026-02-21

## TL;DR

Resistance training with protein helps older adults improve muscle mass and strength by partially reversing age-related changes in amino acid transporters.

## Contribution

This study shows resistance training modifies amino acid transporter profiles in older adults, partially restoring age-related differences.

## Key findings

- Resistance training increased lean leg mass and leg press strength in both young and older adults.
- Older adults had higher membrane LAT1 and SNAT9 at baseline, but training reduced some age-related differences.
- Training produced age-dependent changes in LAT3 and CD98, with distinct effects in young and older participants.

## Abstract

Postprandial stimulation of muscle protein synthesis depends on intracellular amino acid (AA) availability and effective transmembrane AA transporters (AATs). AA transport may be impaired in sedentary and older adults. We compared skeletal muscle AATs between young and older adults and examined effects of resistance training combined with increased protein intake.

Secondary analysis from two randomized controlled trials

Participants were enrolled in trials comparing milk and native whey effects on anabolic signaling, muscle mass, and strength.

Healthy young (n = 32; 14♀/18♂, 20–45 yrs) and older (n = 28; ♀/17♂, 70–80 yrs) adults

Whole-body progressive resistance training 3×/week for 11–12 weeks with protein supplementation.

Pre- and post-intervention assessments included lean leg mass (LLM), one-repetition maximum (1RM) leg press, and AAT protein levels in m. vastus lateralis biopsies. Western blots quantified L-Type Amino Acid Transporter 1 (LAT1) and 3 (LAT3), 4 F2 heavy chain (CD98) and solute carrier 38 member 9 (SNAT9) in cytosol (C), membrane (M) and nuclear (N) fractions. LAT1 membrane (IF-M) and intracellular (IF-IC) distribution were assessed by immunofluorescence.

Training increased LLM by ∼1 kg and 1RM leg press by ∼31% in both groups (p < 0.001). At baseline, older adults showed higher SNAT9M and IF-M LAT1 and lower LAT1C versus young (p < 0.05). Training produced age-dependent changes: LAT3C increased in young (p = 0.39) and CD98M increased in old (p = 0.26) yielding significant time × age interactions (p < 0.05). Across groups, training reduced LAT1 intensity and SNAT9M and increased CD98N (p < 0.01−05). In young participants, IF-IC LAT1 decreased 9 ± 14% (p < 0.05) and CD98N increased 59 ± 97%(p < 0.01). Posttraining, older adults displayed higher IF-M LAT1 and lower CD98M than young (p < 0.05).

Resistance training with protein supplementation improved muscle mass and strength and modified AAT profiles. Age was associated with higher membrane LAT1 and SNAT9, while training attenuated some age-related differences and produced distinct effects on LAT3 and CD98 by age. Exercise may partially counteract age-related alterations in muscle AA transport, with implications for muscle health in aging.

## Linked entities

- **Genes:** SLC7A5 (solute carrier family 7 member 5) [NCBI Gene 8140], SLC43A1 (solute carrier family 43 member 1) [NCBI Gene 8501], SLC3A2 (solute carrier family 3 member 2) [NCBI Gene 6520], SLC38A9 (solute carrier family 38 member 9) [NCBI Gene 153129]

## Full-text entities

- **Genes:** LAT2 (linker for activation of T cells family member 2) [NCBI Gene 7462] {aka HSPC046, LAB, NTAL, WBSCR15, WBSCR5, WSCR5}, SLC43A1 (solute carrier family 43 member 1) [NCBI Gene 8501] {aka LAT3, PB39, POV1, R00504}, EIF2A (eukaryotic translation initiation factor 2A) [NCBI Gene 83939] {aka CDA02, EIF-2A, MST089, MSTP004, MSTP089}, GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 2597] {aka G3PD, GAPD, HEL-S-162eP}, ATF4P3 (activating transcription factor 4 pseudogene 3) [NCBI Gene 643159] {aka ATF4C}, RPS6KB1 (ribosomal protein S6 kinase B1) [NCBI Gene 6198] {aka PS6K, S6K, S6K-beta-1, S6K1, STK14A, p70 S6KA}, SLC7A5 (solute carrier family 7 member 5) [NCBI Gene 8140] {aka 4F2LC, CD98, D16S469E, E16, LAT1, MPE16}, SERPINA1 (serpin family A member 1) [NCBI Gene 5265] {aka A1A, A1AT, AAT, PI, PI1, PRO2275}, SLC38A2 (solute carrier family 38 member 2) [NCBI Gene 54407] {aka ATA2, PRO1068, SAT2, SNAT2}, SLC3A2 (solute carrier family 3 member 2) [NCBI Gene 6520] {aka 4F2, 4F2HC, 4T2HC, CD98, CD98HC, MDU1}, ELP1 (elongator acetyltransferase complex subunit 1) [NCBI Gene 8518] {aka DYS, FD, IKAP, IKBKAP, IKI3, TOT1}, ATF4 (activating transcription factor 4) [NCBI Gene 468] {aka CREB-2, CREB2, TAXREB67, TXREB}, SLC7A8 (solute carrier family 7 member 8) [NCBI Gene 23428] {aka LAT2, LPI-PC1}, SLC36A1 (solute carrier family 36 member 1) [NCBI Gene 206358] {aka Dct1, LYAAT1, PAT1, TRAMD3}, MYH1 (myosin heavy chain 1) [NCBI Gene 4619] {aka HEL71, MYHSA1, MYHa, MyHC-2X/D, MyHC-2x}, DMD (dystrophin) [NCBI Gene 1756] {aka BMD, CMD3B, DXS142, DXS164, DXS206, DXS230}, PARP1 (poly(ADP-ribose) polymerase 1) [NCBI Gene 142] {aka ADPRT, ADPRT 1, ADPRT1, ARTD1, PARP, PARP-1}, PTGS2 (prostaglandin-endoperoxide synthase 2) [NCBI Gene 5743] {aka COX-2, COX2, GRIPGHS, PGG/HS, PGHS-2, PHS-2}
- **Diseases:** Lean leg mass (MESH:D013851), hypertrophy (MESH:D006984), loss in skeletal muscle mass and function (MESH:C536030), inactivity (MESH:C564765), cancer (MESH:D009369), sarcopenia (MESH:D055948), prostate cancer (MESH:D011471)
- **Chemicals:** TBS-T (MESH:C027647), Tween (MESH:D011136), PBS (MESH:D007854), tryptophan (MESH:D014364), PVDF (MESH:C024865), glutamine (MESH:D005973), AA (MESH:D000596), DAKO (-), Glycine (MESH:D005998), Dithiothreitol (MESH:D004229), SDS (MESH:D012967), TBS (MESH:D013725), water (MESH:D014867), Leucine (MESH:D007930), acids (MESH:D000143), OCT (MESH:C051883), methanol (MESH:D000432)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** S2 — Drosophila melanogaster (Fruit fly), Spontaneously immortalized cell line (CVCL_Z232)

## Full text

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## Figures

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## References

43 references — full list in the complete paper: https://tomesphere.com/paper/PMC12945623/full.md

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Source: https://tomesphere.com/paper/PMC12945623