Associations Between Klotho/FGF-Related Protein Expression in Peripheral Blood Mononuclear Cells, Inflammation, and Muscle Function in Middle-Aged Adults with Obesity: A Pilot Study.
Ariadel-Cobo D, Estébanez B, et al. • International journal of molecular sciences • 2026
Obese middle-aged adults exhibited lower Klotho and higher TNF-α levels in PBMCs compared to healthy controls, with PCA revealing that higher Klotho levels were positively associated with better muscle function and lower inflammatory markers, suggesting Klotho/FGF system alterations may reflect biological pathways associated with aging-related phenotypes in obesity.
Key Findings
Results
Obese individuals exhibited significantly lower levels of Klotho protein expression in PBMCs compared to healthy controls.
Study enrolled 45 participants aged 50-60 years: 30 patients with obesity (22F/8M) and 15 healthy controls (11F/4M)
Protein expression was assessed in peripheral blood mononuclear cells (PBMCs)
This was identified as a significant difference between the obese and control groups
The finding suggests Klotho alterations may reflect biological processes linked to obesity-associated premature aging
Results
Obese individuals exhibited significantly higher levels of TNF-α protein expression in PBMCs compared to healthy controls.
TNF-α was assessed alongside Klotho, β-Klotho, FGF19, FGF21, FGF23, and IL-10 in PBMCs
Higher TNF-α in obese participants is consistent with the known pro-inflammatory state of obesity
This difference was identified as a significant finding between obese and control groups
The inverse relationship between Klotho and TNF-α suggests potential anti-inflammatory roles of Klotho
Results
Principal Component Analysis revealed that higher Klotho levels were positively associated with better muscle function and lower inflammatory markers.
PCA was carried out to explore the relationships among variables including body composition, muscle function, and protein expression data
Higher Klotho levels clustered with better muscle function outcomes in the PCA
Higher Klotho levels also clustered with lower inflammatory marker levels in the PCA
These associations suggest Klotho-related alterations may reflect biological processes linked to inflammation and muscle dysfunction in obesity
Methods
Comprehensive body composition and muscle function assessments were conducted alongside PBMC protein expression evaluations.
Assessments included body composition analysis and muscle function tests
Protein expression of Klotho, β-Klotho, FGF19, FGF21, FGF23, TNF-α, and IL-10 were evaluated in PBMCs
The study focused on middle-aged adults (50-60 years) to examine premature aging phenotypes
This was described as a pilot study with an exploratory design, and findings are intended as hypothesis-generating
Conclusions
Alterations in the Klotho/FGF system may reflect biological pathways associated with aging-related phenotypes in obesity rather than direct measures of chronological aging.
The authors caution that findings should be interpreted as hypothesis-generating rather than evidence of causal mechanisms
The exploratory design and limited sample size (n=45) are noted as key limitations
The Klotho/FGF system alterations observed are framed as reflecting 'biological processes linked to inflammation and muscle dysfunction in obesity'
The study specifically investigated premature aging features in middle-aged adults with obesity aged 50-60 years
Ariadel-Cobo D, Estébanez B, González-Arnáiz E, García-Pérez M, Viloria M, Santos A, et al.. (2026). Associations Between Klotho/FGF-Related Protein Expression in Peripheral Blood Mononuclear Cells, Inflammation, and Muscle Function in Middle-Aged Adults with Obesity: A Pilot Study.. International journal of molecular sciences. https://doi.org/10.3390/ijms27041983