# Chronic inflammation as a driving factor for sarcopenia: an update on pathophysiology and future therapeutic targets

**Authors:** Zihan Liang, Lin Zhang

PMC · DOI: 10.3389/fphar.2026.1733798 · Frontiers in Pharmacology · 2026-02-23

## TL;DR

Chronic inflammation plays a key role in sarcopenia, a condition causing muscle loss in older adults, and targeting it could lead to new treatments.

## Contribution

This review systematically examines how chronic inflammation drives sarcopenia and highlights potential therapeutic targets.

## Key findings

- Chronic inflammation contributes to sarcopenia through pathways like oxidative stress and mitochondrial dysfunction.
- Anti-inflammatory interventions and exercise show promise in improving muscle mass and function.
- Cytokines like IL-6 and TNF-α are key players in muscle protein metabolism and could serve as biomarkers.

## Abstract

Sarcopenia is a syndrome characterized by an age-related progressive decline in skeletal muscle mass, strength, and function. It represents a significant public health concern because of its adverse impact on the quality of life and prognosis of older adults. Chronic low-grade inflammation contributes to the pathophysiology of sarcopenia through multiple pathways, including cellular senescence, immunosenescence, oxidative stress, mitochondrial dysfunction, hormonal alterations, and gut microbiota dysbiosis. To elucidate the role of chronic inflammation in the development of sarcopenia, we systematically searched PubMed and Web of Science databases using combinations of keywords such as “sarcopenia,” “chronic inflammation,” “inflammaging,” “cytokines” and “muscle atrophy,” which specifically addressed mechanistic pathways linking inflammation to muscle loss and emerging therapeutic targets. Moreover, obesity, a chronic inflammatory condition, is associated with sarcopenia, leading to sarcopenic obesity, which further exacerbates muscle loss and functional impairment. In terms of interventions, exercise, nutritional supplementation, and combined approaches have demonstrated efficacy in improving muscle mass and function, as well as conferring demonstrable anti-inflammatory benefits. In addition to conventional hormonal therapies, pharmacological strategies, particularly anti-inflammatory agents and treatments targeting inflammatory pathways, show considerable therapeutic promise. This review systematically examines the central role of chronic inflammation in the development and progression of sarcopenia, as well as its underlying mechanistic basis. It also elaborates on the roles of key inflammatory cytokines, such as C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), in regulating muscle protein metabolic balance and their potential utility as biomarkers. A deeper understanding of the relationship between inflammation and sarcopenia will not only help elucidate its complex pathogenesis but also offer critical directions for the future development of early diagnostic tools and targeted anti-inflammatory interventions.

## Linked entities

- **Proteins:** IL6 (interleukin 6)
- **Diseases:** obesity (MONDO:0011122)

## Full-text entities

- **Genes:** STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, JAK3 (Janus kinase 3) [NCBI Gene 3718] {aka JAK-3, JAK3_HUMAN, JAKL, L-JAK, LJAK}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, RB1 (RB transcriptional corepressor 1) [NCBI Gene 5925] {aka OSRC, PPP1R130, RB, p105-Rb, p110-RB1, pRb}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347] {aka GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1}, FBXO32 (F-box protein 32) [NCBI Gene 114907] {aka Fbx32, MAFbx}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, IGF1 (insulin like growth factor 1) [NCBI Gene 3479] {aka IGF, IGF-I, IGFI, MGF}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, TRIM63 (tripartite motif containing 63) [NCBI Gene 84676] {aka CMH31, IRF, MURF1, MURF2, RNF28, SMRZ}, CD163 (CD163 molecule) [NCBI Gene 9332] {aka M130, MM130, SCARI1}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, GHS (Goldenhar syndrome) [NCBI Gene 7971], CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, CASP3 (caspase 3) [NCBI Gene 836] {aka CPP32, CPP32B, SCA-1}, IL12B (interleukin 12B) [NCBI Gene 3593] {aka CLMF, CLMF2, IL-12B, IMD28, IMD29, NKSF}, TIMP2 (TIMP metallopeptidase inhibitor 2) [NCBI Gene 7077] {aka CSC-21K, DDC8}, PRKAB1 (protein kinase AMP-activated non-catalytic subunit beta 1) [NCBI Gene 5564] {aka AMPK, HAMPKb}, PPARGC1A (PPARG coactivator 1 alpha) [NCBI Gene 10891] {aka LEM6, PGC-1(alpha), PGC-1alpha, PGC-1v, PGC1, PGC1A}, MMP2 (matrix metallopeptidase 2) [NCBI Gene 4313] {aka CLG4, CLG4A, MMP-2, MMP-II, MONA, TBE-1}, MSTN (myostatin) [NCBI Gene 2660] {aka GDF8, MSLHP}, IL15 (interleukin 15) [NCBI Gene 3600] {aka IL-15}, FAP (fibroblast activation protein alpha) [NCBI Gene 2191] {aka DPPIV, FAPA, FAPalpha, SIMP}, CDKN1A (cyclin dependent kinase inhibitor 1A) [NCBI Gene 1026] {aka CAP20, CDKN1, CIP1, MDA-6, P21, SDI1}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, IRS1 (insulin receptor substrate 1) [NCBI Gene 3667] {aka HIRS-1}, CDKN2A (cyclin dependent kinase inhibitor 2A) [NCBI Gene 1029] {aka ARF, CAI2, CDK4I, CDKN2, CMM2, INK4}, GGH (gamma-glutamyl hydrolase) [NCBI Gene 8836] {aka GATD10, GH}, IL18 (interleukin 18) [NCBI Gene 3606] {aka IGIF, IL-18, IL-1g, IL1F4}, TRBV20OR9-2 (T cell receptor beta variable 20/OR9-2 (non-functional)) [NCBI Gene 6962] {aka CDR3, TCRBV20S2, TCRBV2O, TCRBV2S2O}, ADIPOQ (adiponectin, C1Q and collagen domain containing) [NCBI Gene 9370] {aka ACDC, ACRP30, ADIPQTL1, ADPN, APM-1, APM1}, CASP8 (caspase 8) [NCBI Gene 841] {aka ALPS2B, CAP4, Casp-8, FLICE, MACH, MCH5}, MAPK8 (mitogen-activated protein kinase 8) [NCBI Gene 5599] {aka JNK, JNK-46, JNK1, JNK1A2, JNK21B1/2, PRKM8}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}, GHRH (growth hormone releasing hormone) [NCBI Gene 2691] {aka GHRF, GRF, INN}, NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 114548] {aka AGTAVPRL, AII, AVP, C1orf7, CIAS1, CLR1.1}, FOXO1 (forkhead box O1) [NCBI Gene 2308] {aka FKH1, FKHR, FOXO1A}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, MRC1 (mannose receptor C-type 1) [NCBI Gene 4360] {aka CD206, CLEC13D, CLEC13DL, MMR, MRC1L1, bA541I19.1}, FCGR2B (Fc gamma receptor IIb) [NCBI Gene 2213] {aka CD32, CD32B, FCG2, FCGR2, IGFR2}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, CASP1 (caspase 1) [NCBI Gene 834] {aka ICE, IL1BC, P45}, TNFSF12 (TNF superfamily member 12) [NCBI Gene 8742] {aka APO3L, DR3LG, TNF12, TNLG4A, TWEAK}, CD28 (CD28 molecule) [NCBI Gene 940] {aka IMD123, Tp44}, SLC2A4 (solute carrier family 2 member 4) [NCBI Gene 6517] {aka GLUT4}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, IL13 (interleukin 13) [NCBI Gene 3596] {aka IL-13, P600}, FOXO3 (forkhead box O3) [NCBI Gene 2309] {aka AF6q21, FKHRL1, FKHRL1P2, FOXO2, FOXO3A}, FNDC5 (fibronectin type III domain containing 5) [NCBI Gene 252995] {aka FRCP2, irisin}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, TRAF6 (TNF receptor associated factor 6) [NCBI Gene 7189] {aka MGC:3310, RNF85}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, MYH14 (myosin heavy chain 14) [NCBI Gene 79784] {aka DFNA4, DFNA4A, FP17425, MHC16, MYH17, NMHC II-C}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, IGFBP3 (insulin like growth factor binding protein 3) [NCBI Gene 3486] {aka BP-53, IBP-3, IBP3, IGFBP-3}
- **Diseases:** Sarcopenia (MESH:D055948), SMA (MESH:D009133), Chronic inflammation (MESH:D007249), trauma (MESH:D014947), disease (MESH:D004194), T-cell dysfunction (MESH:C536780), IR (MESH:C537629), prostate cancer (MESH:D011471), loss (MESH:D016388), fibrosis (MESH:D005355), impaired physical function (MESH:D059445), fractures (MESH:D050723), Mitochondrial injury (MESH:D028361), geriatric syndrome (MESH:D013577), MPS (MESH:D019042), nonalcoholic fatty liver disease (MESH:D065626), AD (MESH:D000544), functional decline (MESH:D060825), diminished muscle strength (MESH:D015354), fibrosarcoma (MESH:D005354), reduced (MESH:D001523), cancer (MESH:D009369), diabetes (MESH:D003920), weakness (MESH:D018908), gut dysbiosis (MESH:D064806), ICD-10-CM (OMIM:252500), atrophy (MESH:D001284), disuse atrophy (MESH:D020966), weight gain (MESH:D015430), Obesity (MESH:D009765), loss of independence (MESH:D064129), cachexia (MESH:D002100), fatigue resistance (MESH:D005221), COPD (MESH:D029424), polycythemia (MESH:D011086), type II fiber atrophy (MESH:D014897), vitamin D deficiency (MESH:D014808), overweight (MESH:D050177), stroke (MESH:D020521), metabolic dysfunction (MESH:D008659), hypogonadism (MESH:D007006), muscle fiber damage (MESH:C563545), inactivity (MESH:C564765), metabolic dysregulation (MESH:D021081), muscle mass (MESH:C536030), skeletal muscle disorder (MESH:D005207), visceral adiposity (MESH:D007418), Frailty (MESH:D000073496), arthritis (MESH:D001168), rheumatoid arthritis (MESH:D001172), death (MESH:D003643), Malnutrition (MESH:D044342), hyperinsulinemia (MESH:D006946), SASP (MESH:D008579), muscle hypertrophy (MESH:C536106), infection (MESH:D007239), leptin resistance (OMIM:614962), cardiovascular disease (MESH:D002318), Crohn's disease (MESH:D003424), colitis (MESH:D003092)
- **Chemicals:** fats (MESH:D005223), Vitamin D (MESH:D014807), phosphorus (MESH:D010758), TCZ (MESH:C502936), methylxanthine (MESH:C008514), Theophylline (MESH:D013806), SB203580 (MESH:C093642), EPA (MESH:D015118), leucine (MESH:D007930), Testosterone (MESH:D013739), FFA (MESH:D005230), catechins (MESH:D002392), CLA (MESH:D044243), 8-OHdG (MESH:D000080242), ceramides (MESH:D002518), IFX (MESH:D000069285), superoxide (MESH:D013481), -blockers (-), PUFAs (MESH:D005231), amino acid (MESH:D000596), cholecalciferol (MESH:D002762), 8-isoprostane (MESH:C075750), carbohydrates (MESH:D002241), fatty acid (MESH:D005227), ATP (MESH:D000255), lipid (MESH:D008055), HMB (MESH:C004961), DHEA (MESH:D003687), LPS (MESH:D008070), DHA (MESH:D004281), p-cresol (MESH:C032538), hs (MESH:D006859), flavonoids (MESH:D005419), glucose (MESH:D005947), calcium (MESH:D002118), sulfuric acid (MESH:C033158), ROS (MESH:D017382)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Rattus norvegicus (brown rat, species) [taxon 10116], Rodentia (rodent, order) [taxon 9989], Homo sapiens (human, species) [taxon 9606]

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## References

235 references — full list in the complete paper: https://tomesphere.com/paper/PMC12968189/full.md

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Source: https://tomesphere.com/paper/PMC12968189