Unraveling the Relationship Between the Inflammaging Phenomenon and Telomere Length, Associated with Obesity and Dynapenia in Older Men: Pilot Study

This study aimed to evaluate the relationship between telomere length and systemic inflammatory profiles in older man individuals with different body compositions and the presence or absence of dynapenia, focusing on elucidating how inflammatory cytokines influence telomere shortening.

A total of 66 older men aged between 60 and 85 years were recruited from a community-dwelling cohort and stratified into four groups based on body mass index (BMI) and the presence of dynapenia, defined as reduced grip strength below the cut-off established for age and sex: non-dynapenic eutrophic (ND-E, n=21), non-dynapenic obese (ND-O, n=21), dynapenic eutrophic (D-E, n=13), and dynapenic obese (D-O, n=11). BMI was calculated according to the WHO classification, and dynapenia was assessed using a digital handgrip dynamometer. Blood samples were collected from fasting participants, and plasma levels of inflammatory cytokines, including IL-6, IL-10, IFN-γ, TNF-α, and IL-12p70, were quantified using a BioLegend™ multiplex kit. Telomere length was measured from peripheral blood leukocytes using a monochrome multiplex quantitative PCR technique, which provides relative telomere length normalized to a single-copy reference gene. The results were analyzed using multiple regression models to determine the association between telomere length and cytokine concentrations. 

The ND-E group showed a pronounced negative correlation between telomere length and pro-inflammatory cytokines IL-6 and IFN-γ (r²=0.610; p0.0001). In the D-E group, IL-12p70 emerged as the primary cytokine associated with shorter telomeres (r²=0.483; p=0.025), highlighting a distinct inflammatory profile compared to non-dynapenic groups. Conversely, in the D-O group, the relationship was more complex, with telomere length being inversely correlated with TNF-α (r²=0.932; p=0.014) and positively correlated with IL-10 levels (r²=0.932; p0.0001). No significant correlations were found in the ND-O group.

Telomere shortening in elderly individuals is influenced by pro-inflammatory cytokines, particularly IL-6 and IFN-γ, in eutrophic non-dynapenic individuals. The distinct cytokine profiles observed in dynapenic groups suggest adaptive inflammatory responses in the context of muscle loss, which are further modulated by obesity. 

These findings highlight the role of the systemic inflammatory milieu in determining telomere dynamics and suggest that targeting specific cytokine pathways could provide therapeutic strategies for preserving telomere integrity and mitigating frailty in aging populations.