Does Lifelong Exercise Counteract Low-Grade Inflammation Associated with Aging? A Systematic Review and Meta-Analysis
Authors: Pérez-Castillo Iñigo M. , Rueda Ricardo , Bouzamondo Hakim , Aparicio-Pascual Diego , Valiño-Marques Alberto , López-Chicharro Jose , Segura-Ortiz Felipe 
Published: January 2025

Abstract
Background
Aging is associated with sustained low-grade inflammation, which has been linked to age-related diseases and mortality. Long-term exercise programs have been shown to be effective to for attenuating this process; however, subsequent detraining might negate some of these benefits. Master athletes, as a model of lifelong consistent exercise practice, have been suggested to present similar inflammatory profiles to untrained young adults. Nonetheless, it is unclear whether maintaining training habits throughout life can completely counteract low-grade inflammation associated with aging.

Objectives
We aimed to systematically evaluate comparisons of baseline inflammatory profiles in Master athletes, untrained middle-aged and older adults, and untrained young individuals to elucidate whether lifelong exercise can counteract low-grade inflammation associated with aging.

Methods
A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, and a protocol was prospectively registered in PROSPERO (CRD42024521339). Studies reporting baseline systemic levels of proinflammatory and anti-inflammatory markers in Master athletes and untrained controls were eligible for inclusion. A total of six databases (PubMed [MEDLINE], Embase, Cochrane Central Register of Controlled Trials [CENTRAL], Scopus, SPORTDiscus, and Web of Science [WoS]) were searched in September 2024, and studies were independently screened by two reviewers. Risk of bias was assessed using an adapted version of the Joanna Briggs Institute Critical Appraisal tool for cross-sectional trials, and random-effect meta-analyses of standardized mean differences (SMDs) of inflammatory markers were conducted to evaluate comparisons between Master athletes and age-matched untrained middle-aged and older adults as well as Master athletes and young untrained subjects. Subgroup analyses were performed based on exercise intensity and type, and participants’ sex.

Results
A total of 17 studies (n = 649 participants) were included both in qualitative and quantitative synthesis. Lifelong exercise appears to attenuate increases in baseline C-reactive protein, and to elevate anti-inflammatory interleukin (IL)-10 levels compared with untrained middle-aged and older adults (C-reactive protein: SMD − 0.71, 95% confidence interval − 0.97, − 0.45, I2 0%, p = 0.78; IL-10: SMD 1.44, 95% confidence interval 0.55, 2.32, I2 87%, p < 0.00001). Statistical significance was maintained in C-reactive protein and IL-10 sub-analyses. No difference in tumor necrosis factor-α levels was observed between Master athletes and untrained middle-aged and older adults (SMD 0.40, 95% confidence interval − 0.15, 0.96, I2 72%, p = 0.0008). A trend towards decreased IL-6 levels in Master athletes was shown in pooled analyses comparing untrained middle-aged and older adults, and rendered statistically significant in sub-analyses. However, comparisons with young untrained adults indicated that Master athletes still present with elevated levels of tumor necrosis factor-α and IL-6, along with decreased IL-10.

Conclusions
Master athletes might exhibit a more anti-inflammatory profile denoted by decreased baseline circulating levels of C-reactive protein and, potentially, IL-6, along with increased IL-10 compared with healthy age-matched untrained peers. However, lifelong exercise might still be insufficient to completely counteract age-related changes in tumor necrosis factor-α, IL-6, and IL-10, as shown in comparisons with untrained young adults.