# Skeletal Muscle and Circulating microRNAs Adaptations to 12-Week HIIT With or Without L-Citrulline in Obese Older Adults

PMID: 41933456
Journal: Journal of cachexia, sarcopenia and muscle
Published: 2026 Apr
Authors: Mercier-Guery A, Millet M, Croset M, Marcangeli V, Dulac M, Carvalho LP, Hajj-Boutros G, Gaudreau P, Morais JA, Gouspillou G, Noirez P, Rousseau JC, Chapurlat R, Aubertin-Leheudre M

## Question

Does 12 weeks of supervised HIIT, with or without L-citrulline supplementation, change muscle and circulating microRNA expression in older adults with obesity, and are those microRNA changes associated with clinical and biological adaptations?

## Summary

In older adults with obesity who completed supervised elliptical HIIT, adding daily L-citrulline altered some muscle and blood microRNAs and those changes were linked with body composition, functional, muscle-power, IGF-1, leptin, adiponectin, and insulin-sensitivity changes. The paper is mechanistic and exploratory, so it is more useful for internal adaptation context than for making direct user-facing workout claims.

## Population

- Older men and women with obesity and/or dynapenia in a supervised HIIT trial subset
- Sample size: 68
- Age: 67.2 +/- 5.2 years
- Sex: 36 women, 32 men
- Fitness level: Older, obese/dynapenic, completing supervised HIIT
- Health status: Relatively healthy older adults with obesity or dynapenia

## Methodology

- Secondary exploratory analysis of a double-blind randomized interventional trial
- 12 weeks
- Supervised exercise sessions with pre/post blood, adipose, and muscle biopsy sampling
- Randomized and controlled study design.

## Protocol

- Elliptical HIIT.
- Modality: Elliptical.
- Work intervals: 30 seconds.
- Recovery: 90 seconds.
- Sets or repetitions: About 10 repeated bouts.
- Intensity: 80%-85% HRmax or Borg >17.
- Session duration: 30 minutes.
- Frequency: 3 times/week.
- Program length: 12 weeks.
- Progression: Speed and resistance adjusted to maintain target HR/RPE.
- Same HIIT plus placebo.
- Modality: Elliptical.
- Work intervals: 30 seconds.
- Recovery: 90 seconds.
- Sets or repetitions: About 10 repeated bouts.
- Intensity: 80%-85% HRmax or Borg >17.
- Session duration: 30 minutes.
- Frequency: 3 times/week.
- Program length: 12 weeks.
- Progression: Same supervised adjustment; supplement differed.

## Outcomes

### Myo-microRNAs
Status: no clear change
Myo-microRNAs and muscle-related microRNAs were not altered by HIIT with or without citrulline.

### miR-504-5p
Status: improved
HIIT plus citrulline decreased muscle miR-504-5p compared with placebo and this correlated with lower body fat, better functional capacities, muscle power, and higher IGF-1.

p=0.022 for decrease; correlations around r=-0.6, p<0.05

### Response biomarkers
Status: mixed
Several muscle and serum microRNA changes were associated with favorable body composition, functional, metabolic, or hormone changes, but mostly in subgroup or association analyses.

Selected subgroup p values <=0.05

## Practical Insights

- For internal generation, 30-second hard efforts with 90-second recoveries are a documented older-adult elliptical structure when supervised.
- The response to HIIT may vary by sex, age, BMI, dynapenic status, and supplement context; avoid one-size-fits-all claims.
- This paper supports biomarker and adaptation context, not direct frontend promises.

## Limitations

- Secondary exploratory analysis
- No nonexercise control or citrulline-only group
- Small NGS and biopsy subsets
- Multiple subgroup and association analyses
- Device-logged work/power dose not available

## Safety And Adherence

- No adverse event detail was reported in this secondary analysis.
- Authors caution that external validity is limited to relatively healthy older adults with obesity and limited comorbidities.

## Original Sources

- [PubMed](https://pubmed.ncbi.nlm.nih.gov/41933456/) (pubmed)
- [DOI](https://doi.org/10.1002/jcsm.70267) (doi)
- [PMC full text](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13051928/) (full text)

## Agent Guidance

Preserve the paper-level scope of this note. Do not generalize beyond the population, protocol, measured outcomes, and limitations above.