# The Muscle Function Deficit Concept and Inflammaging

**Authors:** Giada Mariano, Matteo Candeloro, Raffaello Pellegrino, Roberto Paganelli, Angelo Di Iorio

PMC · DOI: 10.3390/biomedicines14020383 · Biomedicines · 2026-02-06

## TL;DR

This paper introduces a new concept called Skeletal Muscle Function Deficit (SMFD) to better understand muscle aging and its link to inflammation.

## Contribution

The novel contribution is the SMFD concept, which unifies muscle quality and mass into a single functional definition linked to inflammaging.

## Key findings

- SMFD is associated with geriatric outcomes like disability risk and falls.
- Inflammaging connects muscle and neural aging through inflammatory mediators.
- SMFD enables early detection and risk stratification for muscle deterioration.

## Abstract

Aging-related muscle dysfunction has been conceptualized through the model of sarcopenia, but it embraces several other characteristics, e.g., dynapenia, myosteatosis, and powerpenia. Our perspective reframes muscle aging from a different point of view, the Skeletal Muscle Function Deficit (SMFD), a unifying approach that integrates muscle quality and mass into a single functional definition. An SMFD score has been adopted in the InCHIANTI study against many geriatric outcomes, such as risk of disability, physical performance, hospitalizations and falls, and incidence of major diseases, highlighting its potential value as a primary indicator of muscle failure and/or of healthy aging. At the core of SMFD lies inflammaging, the chronic, low-grade, age-related inflammation, linking functional outcomes to muscular and neural aging. Inflammatory mediators alter the anabolic/catabolic balance, accelerate myosteatosis, impair neuromuscular junction, and influence denervation. These findings support the idea of a common pathway that links neuro-muscular deficit and inflammation, which simultaneously targets cortical motor circuits, spinal motor neurons, peripheral nerves, and muscle fibers. The SMFD approach facilitates early detection, risk stratification, and possible intervention for muscle deterioration with aging.

## Full-text entities

- **Genes:** IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 114548] {aka AGTAVPRL, AII, AVP, C1orf7, CIAS1, CLR1.1}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, ADIPOQ (adiponectin, C1Q and collagen domain containing) [NCBI Gene 9370] {aka ACDC, ACRP30, ADIPQTL1, ADPN, APM-1, APM1}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}
- **Diseases:** muscle weakness (MESH:D018908), reduced quality of life (MESH:D001523), muscle failure (MESH:D051437), impairments (MESH:D060825), age (MESH:D019588), injury to (MESH:D014947), neurodegenerative (MESH:D019636), clinical disease (MESH:D004194), Inflammation (MESH:D007249), Sarcopenia (MESH:D055948), decline of mobility (MESH:D014086), hip osteoarthritis (MESH:D015207), muscle regeneration (MESH:D019042), Parkinson's disease (MESH:D010300), mitochondrial dysfunction (MESH:D028361), neuromuscular decline (MESH:D009468), neuro-muscular deficit (MESH:D009461), fat (MESH:D004620), neuromuscular junction deterioration (MESH:D020511), chronic (MESH:D002908), mobility limitation (MESH:D051346), neuromuscular deterioration (MESH:D020879), Frail (MESH:D000073496), decline of skeletal muscle (MESH:D005207), damage (MESH:D020263), cognitive deterioration (MESH:D003072), disability (MESH:D009069), muscle mass and strength loss (MESH:C536030), loss of muscle power and explosiveness (MESH:D007174), heart failure (MESH:D006333), falls (MESH:C537863), loss of independence (MESH:D064129), excess adiposity (MESH:D018205), sarcopenic obesity (MESH:D009765), stroke (MESH:D020521), dementia (MESH:D003704), dysfunction (MESH:D006331), impaired self-sufficiency (MESH:D012652), fatigability (MESH:D009759), peripheral nerve deterioration (MESH:D010523), loss of muscle strength (MESH:D009135)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12938328/full.md

## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC12938328/full.md

## References

67 references — full list in the complete paper: https://tomesphere.com/paper/PMC12938328/full.md

---
Source: https://tomesphere.com/paper/PMC12938328