Is stretching an appropriate control for studies on exercise immunology in older adults? A systematic review

Active muscle contraction is assumed to be essential in the anti-inflammatory effect of physical exercise, also in older adults. Although stretching does not involve active muscle contractions, its (anti)inflammatory effects remain unclear. This systematic review aims to determine whether stretching affects the inflammatory profile of older adults and if it can be considered as an appropriate control intervention for exercise immunology studies.

This systematic review was registered in PROSPERO (CRD42023388920) and conducted in accordance with PRISMA guidelines. PubMed and Web of Science were systematically screened for articles describing the effect of muscle stretching on the inflammatory profile (immune cell proportions, cytokines, oxidative markers, and inflammatory gene expression in muscle/immune cells) in older adults. A methodological quality assessment was performed using the ROB2 tool and effect sizes (ES) were calculated.

Nine randomized controlled trials were included, all showing sufficient methodological quality and reporting effects on basal levels of inflammation. Muscle stretching had no effect on the number of naïve, memory, and senescence-prone T-cells or circulating inflammatory markers CRP and IL-6 neither on most studied oxidative stress markers (SOD, NO, VCAM, ICAM, PTX3, OX-LDL, MDA, HNE, nitrotyrosine, ox-LDL, and protein carbonyls). However, the oxidative stress marker LPO increased (ES=0.76) while CAT, ROS, fibrinogen, and MDA-LDL decreased (ES between -0.50 and -0.63) after stretching in older persons with chronic diseases. Contradictory results were found for TNF-alpha and gene expression levels. One study observed no changes in circulating TNF-alpha after stretching in healthy women, while another study showed an increase in muscle gene expression of TNF-alpha (ES=1.60) as well as circulating TNF-alpha (ES=0.64) in men with peripheral arterial disease. Regarding gene expression changes in pro/anti-inflammatory related genes, one study analysing RNA extracted from peripheral blood mononuclear cells showed stretching-induced increases (fold change≥1.5) or decreases (fold change≤0.67), while another study using RNA from buffy coat samples demonstrated no effect on gene expression.

Passive or active types of muscle stretching appears to be a suitable active control for exercise immunology studies in older populations. However, in populations with peripheral artery disease with stretching may affect the inflammatory profile, possibly due to a higher overall inflammatory status.