# Resistance-based exercise restores muscle health in dialysis patients

**Authors:** Piush Srivastava, Sunil Kumar Singh, Rakesh Sathish Nair, Saket Jha, Navin Viswakarma, Deepti Srivastava, Greg Hachaj, Stephen T. Bartlett, Ilaria Santi, Aslam Ejaz, Robert W. Motl, Enrico Benedetti, Sandeep Kumar, Ajay Rana

PMC · DOI: 10.1007/s10974-026-09727-0 · Journal of Muscle Research and Cell Motility · 2026-03-14

## TL;DR

Resistance-based exercise improves muscle health in dialysis patients by boosting genes and proteins related to muscle repair and energy production.

## Contribution

This study identifies molecular mechanisms by which resistance-based exercise restores muscle health in dialysis patients.

## Key findings

- Exercise upregulates genes linked to muscle stemness, regeneration, and differentiation.
- Exercise increases mitochondrial proteins involved in oxidation and energy production.
- Exercise enhances glucose uptake and fatty acid metabolism for energy generation.

## Abstract

Chronic kidney disease (CKD) and end-stage renal disease (ESRD) are serious health concerns worldwide that require regular dialysis before a kidney transplant for a better quality of life. Due to aging and frailty, dialysis patients are often limited in physical activity, which can lead to multiple health complications and sometimes result in patient death. Therefore, maintaining muscle health is crucial for individuals undergoing dialysis. We recently reported that personalized resistance-based exercise can improve frailty in dialysis patients; however, the molecular mechanisms underlying its effects on muscle health remain unknown. RNA-Seq analysis revealed that exercise upregulates genes associated with muscle stemness, regeneration, and differentiation. Furthermore, our study demonstrated that exercise upregulates mitochondrial proteins involved in the oxidation of organic compounds and mitochondrial function in muscle. Moreover, we observed that exercise increased energy production via glucose uptake, glycogenesis, and fatty acid metabolism. These results suggest that personalized resistance-based muscle therapy in dialysis patients restores the expression of genes and proteins associated with muscle stemness, regeneration, differentiation, and energy generation.

The online version contains supplementary material available at 10.1007/s10974-026-09727-0.

## Linked entities

- **Diseases:** chronic kidney disease (MONDO:0005300), end-stage renal disease (MONDO:0004375)

## Full-text entities

- **Genes:** PRKAG3 (protein kinase AMP-activated non-catalytic subunit gamma 3) [NCBI Gene 53632] {aka AMPKG3, SMGMQTL}, GYS1 (glycogen synthase 1) [NCBI Gene 2997] {aka GSY, GYS}, VCAM1 (vascular cell adhesion molecule 1) [NCBI Gene 7412] {aka CD106, INCAM-100}, SLC2A4 (solute carrier family 2 member 4) [NCBI Gene 6517] {aka GLUT4}, NR1D1 (nuclear receptor subfamily 1 group D member 1) [NCBI Gene 9572] {aka EAR1, REVERBA, REVERBalpha, THRA1, THRAL, ear-1}, CPT1A (carnitine palmitoyltransferase 1A) [NCBI Gene 1374] {aka CPT I, CPT1, CPT1-L, CPTI-L, L-CPT1}, ACO2 (aconitase 2) [NCBI Gene 50] {aka ACONM, HEL-S-284, ICRD, OCA8, OPA9}, PRKAB1 (protein kinase AMP-activated non-catalytic subunit beta 1) [NCBI Gene 5564] {aka AMPK, HAMPKb}, PAX7 (paired box 7) [NCBI Gene 5081] {aka CMYO19, CMYP19, HUP1, MYOSCO, PAX7B, RMS2}, DES (desmin) [NCBI Gene 1674] {aka CDCD3, CSM1, CSM2, LGMD1D, LGMD1E, LGMD2R}, PPP1R3D (protein phosphatase 1 regulatory subunit 3D) [NCBI Gene 5509] {aka PPP1R6}, GBE1 (1,4-alpha-glucan branching enzyme 1) [NCBI Gene 2632] {aka APBD, GBE, GSD4}, CYTB (cytochrome b) [NCBI Gene 4519] {aka MTCYB}, COX2 (cytochrome c oxidase subunit II) [NCBI Gene 4513] {aka COII, MTCO2}, PINK1 (PTEN induced kinase 1) [NCBI Gene 65018] {aka BRPK, PARK6}, NR4A3 (nuclear receptor subfamily 4 group A member 3) [NCBI Gene 8013] {aka CHN, CSMF, MINOR, NOR1}, ETFRF1 (electron transfer flavoprotein regulatory factor 1) [NCBI Gene 144363] {aka LYRM5}, ENO3 (enolase 3) [NCBI Gene 2027] {aka GSD13, MSE}, FABP1 (fatty acid binding protein 1) [NCBI Gene 2168] {aka FABPL, L-FABP}, DMD (dystrophin) [NCBI Gene 1756] {aka BMD, CMD3B, DXS142, DXS164, DXS206, DXS230}, ND5 (NADH dehydrogenase subunit 5) [NCBI Gene 4540] {aka MTND5}, COX3 (cytochrome c oxidase subunit III) [NCBI Gene 4514] {aka COIII, MTCO3}, MYH6 (myosin heavy chain 6) [NCBI Gene 4624] {aka ASD3, CMD1EE, CMH14, MYHC, MYHCA, SSS3}, ND4 (NADH dehydrogenase subunit 4) [NCBI Gene 4538] {aka MTND4}, GYS2 (glycogen synthase 2) [NCBI Gene 2998], METTL3 (methyltransferase 3, N6-adenosine-methyltransferase complex catalytic subunit) [NCBI Gene 56339] {aka IME4, M6A, MT-A70, Spo8, hMETTL3}, ATP5ME (ATP synthase membrane subunit e) [NCBI Gene 521] {aka ATP5I, ATP5K}, ND4L (NADH dehydrogenase subunit 4L) [NCBI Gene 4539] {aka MTND4L}, LMNA (lamin A/C) [NCBI Gene 4000] {aka CDCD1, CDDC, CMD1A, CMT2B1, EMD2, FPL}, ND2 (NADH dehydrogenase subunit 2) [NCBI Gene 4536] {aka MTND2}, TRAP1 (TNF receptor associated protein 1) [NCBI Gene 10131] {aka HSP 75, HSP75, HSP90L, TRAP-1}, MYOD1 (myogenic differentiation 1) [NCBI Gene 4654] {aka CMYO17, CMYP17, MYF3, MYOD, MYODRIF, PUM}, EMD (emerin) [NCBI Gene 2010] {aka CMD3C, EDMD, LEMD5, STA}, COX4I1 (cytochrome c oxidase subunit 4I1) [NCBI Gene 1327] {aka COX IV-1, COX4, COX4-1, COXIV, COXIV-1, MC4DN16}, SLC25A25 (solute carrier family 25 member 25) [NCBI Gene 114789] {aka MCSC, PCSCL, SCAMC-2, SCAMC2}, SLC2A1 (solute carrier family 2 member 1) [NCBI Gene 6513] {aka CSE, DYT17, DYT18, DYT9, EIG12, GLUT}, CBFA2T3 (CBFA2/RUNX1 partner transcriptional co-repressor 3) [NCBI Gene 863] {aka ETO2, MTG16, MTGR2, RUNX1T3, ZMYND4}, UGP2 (UDP-glucose pyrophosphorylase 2) [NCBI Gene 7360] {aka DEE83, EIEE83, SVUGP2, UDPG, UDPGP, UDPGP2}, ND1 (NADH dehydrogenase subunit 1) [NCBI Gene 4535] {aka MTND1}, ACTN3 (actinin alpha 3) [NCBI Gene 89] {aka ACTN3D}, ND6 (NADH dehydrogenase subunit 6) [NCBI Gene 4541] {aka MTND6}
- **Diseases:** ETC (MESH:D028361), anxiety (MESH:D001007), Muscle frailty (MESH:D000073496), CKD (MESH:D051436), kidney failure (MESH:D051437), ESRD (MESH:D007676), bodily pain (MESH:D010146), fatigue (MESH:D005221), sleep disturbance (MESH:D012893), loss of lean mass (MESH:D013851), cardiac or pulmonary disease (MESH:D006331), death (MESH:D003643), disability in movement (MESH:D009069), depression (MESH:D003866), Loss of muscle mass and strength (MESH:C536030), musculoskeletal disorders (MESH:D009140)
- **Chemicals:** TCA (MESH:D014238), TRIzol (MESH:C411644), xylene (MESH:D014992), lipids (MESH:D008055), glucose (MESH:D005947), gold (MESH:D006046), alcohol (MESH:D000438), DAPI (MESH:C007293), sodium citrate (MESH:D000077559), ATP (MESH:D000255), hematoxylin (MESH:D006416), carbohydrates (MESH:D002241), m6A (MESH:C005955), fatty acid (MESH:D005227), isocitrate (MESH:C034219), organic compounds (MESH:D009930), AMP (MESH:D000249), Triton X (MESH:D017830), PBS (MESH:D007854), 3,3'-Diaminobenzidine (MESH:D015100), Glycogen (MESH:D006003), formalin (MESH:D005557), citrate (MESH:D019343), paraffin (MESH:D010232), 3'-Diaminobenzidine (-)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]
- **Mutations:** T94A

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12989000/full.md

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Source: https://tomesphere.com/paper/PMC12989000