Resistance Exercise Intervention Restores Functional Capacity and Improves Frailty Biomarkers in Centenarians

Abstract

Background: Centenarians comprise an age group characterized by exceptional longevity and low age-associated pathologies. However, they still experience physiological decline, and different studies have linked frailty to this population. Exercise interventions reverse frailty and improve functional capacity, but no studies have addressed the effect of an intervention in centenarians. In this study, we assessed the impact of a 12-week resistance exercise intervention in a group of centenarians and characterized their functional capacity as well as the expression of several molecular biomarkers associated with frailty.

Methods: A total of 19 centenarians were enrolled, but 7 of them did not complete the study. The remaining 12 centenarians were randomly assigned to the control or intervention group, which was a 12-week resistance exercise intervention. Molecular biomarkers were measured by qRT-PCR and ELISA.

Results: The intervention group improved their functional capacity measured by Short Physical Performance Battery (SPPB) (post 5.0 vs 2.3 in pre) and Physical Performance and Mobility Examination (PPME) (6.5 vs 3.8), as well as in frailty status studied by Fried Frailty Phenotype (3.0 vs 3.8) and Frailty Trait Scale 5 (FTS5) (post 30.7 vs 34.0 in pre) scales. ANCOVA revealed that the resistance training led to significant improvements in functional capacity scales SPPB (p = 0.01) and PPME (p < 0.001), as well as Fried Frailty Phenotype (p = 0.001) and FTS5 (p = 0.05). Biomarkers related to frailty (EGR1, miR194-5p, miR125b-5p and miR454-3p) and inflammation (IL-6 and IL-1β) showed different expression patterns in centenarians (n = 19) compared to both old (n = 44, average of 79 years old) and young adults (n = 34, average of 29 years old) groups. Notably, the intervention was associated with improvements in frailty and inflammation biomarkers expression. Finally, correlation analyses showed significant associations between all functional and frailty variables, with SPPB correlating with miR454-3p (ρ = 0.73) and FTS5 correlating with miR454-3p (ρ = -0.83), IL-6 (ρ = 0.60) and miR125b-5p (ρ = -0.55).

Conclusions: Our results revealed that resistance exercise intervention enhances functional status and reduces frailty in centenarians, and this is associated with improvements in frailty and inflammation biomarkers.

Keywords: centenarians; frailty; molecular biomarkers; resistance exercise.

FIGURE 1

Description of populations of the study and the impact of the intervention (A) Description of centenarians (n = 19), old (n = 44) and young adults (n = 34) populations. (B) Table with functional and frailty scales in control and intervention groups before and after 12‐week resistance exercise intervention. ANCOVA analysis of clinical data. (C, D) Individual graphs and results in functional and frailty scales in control and intervention group pre and post intervention (E, F) mRNA expression of EGR1, miR194‐5p, miR125‐5p and miR454‐3p levels in young (n = 34) old (n = 44) and centenarians (n = 19) groups. (F) expression of IL‐6 and IL‐1β in same groups.

FIGURE 2

Frailty biomarkers in intervention. (A, B) Expression levels of markers in entire pre/post centenarian cohort (n = 19). (C, D) mRNA expression of indicated biomarkers in pre and post exercise in intervention group (n = 6). (E, F) mRNA expression levels of markers in pre and post condition in control group (n = 6). (G) EGR1 protein expression by ELISA in pre/post samples of control and exercise group (n = 6 each). (H) Spearman's correlations between clinical variables and markers expression.