Analysis of the potential association between physical activity and skin autofluorescence: a systematic review.
Clinical Snapshot
PICO Framework
| P — Population | General adult population (all ages, both sexes, with and without chronic disease) |
| I — Intervention | Physical activity (PA) or exercise of any type, frequency, intensity, or duration |
| C — Comparator | Lower levels of physical activity, sedentary behaviour, or no exercise |
| O — Outcomes | Skin autofluorescence (SAF) as a surrogate marker of advanced glycation end-product (AGE) accumulation, with downstream relevance to cardiovascular disease (CVD) risk |
Bottom Line
This systematic review of 17 studies examines whether physical activity (PA) is associated with lower skin autofluorescence (SAF), a non-invasive proxy for advanced glycation end-product (AGE) tissue accumulation and an emerging cardiovascular risk biomarker. Using vote counting by direction of effect — the appropriate synthesis method when meta-analysis is not feasible — the review finds that 58.8% of studies reported a statistically significant inverse association between PA and SAF, with no study reporting a harmful association. This directional consistency is biologically plausible: exercise may reduce AGE accumulation through improved glycaemic control, reduced oxidative stress, and enhanced AGE clearance mechanisms. However, the GRADE certainty of evidence is rated low, no pooled effect size is available, and 41.2% of studies showed non-significant results. Predominantly observational study designs preclude causal inference, and residual confounding — particularly from diet, BMI, and metabolic health — cannot be excluded. For Australian clinicians, this review reinforces existing RACGP-endorsed PA promotion for cardiovascular risk reduction but does not provide sufficient evidence to introduce SAF monitoring as a routine clinical tool or to modify current practice beyond established guidelines. Well-designed randomised controlled trials with SAF as a pre-specified outcome are needed to establish causality and quantify effect magnitude.
Key Findings
P Value: Not reported at the review level; individual study significance thresholds not detailed in abstract
Effect Size: No pooled effect size calculated. Vote counting: 58.8% of studies (approximately 10 of 17) reported a statistically significant inverse association between higher PA levels and lower SAF; 41.2% (approximately 7 of 17) reported non-significant results. No study reported a positive association.
Primary Outcome: Skin autofluorescence (SAF) as a non-invasive measure of advanced glycation end-product (AGE) tissue accumulation
Nnt Or Sensitivity: Not applicable; no quantitative synthesis performed. The review is prognostic/associative in nature. SAF is a surrogate biomarker, not a clinical endpoint, so NNT cannot be derived from this evidence base.
Confidence Interval: Not calculable; no meta-analysis performed
Clinical Application
SAF measurement via AGE Reader (Diagnoptics Technologies) or equivalent devices is non-invasive, rapid (approximately 1 minute), and reproducible, but devices are not universally available in primary care settings. PA promotion is universally feasible and low-cost. The review supports existing PA promotion strategies but does not provide sufficient evidence to introduce SAF monitoring as a PA response biomarker in routine clinical workflows. In Australia, PA promotion aligns with RACGP guidelines for preventive care and the Australian Physical Activity and Sedentary Behaviour Guidelines (150–300 minutes of moderate-intensity PA per week for adults). SAF devices are not currently listed on the Medicare Benefits Schedule (MBS) for routine cardiovascular risk assessment, and AGE-lowering pharmacotherapy is not a PBS-listed indication. The TGA has not approved SAF-based devices for specific diagnostic indications beyond research contexts. This review provides mechanistic support for existing RACGP-endorsed PA counselling in cardiovascular risk reduction but does not justify new clinical pathways or funding submissions at this evidence level. Australian clinicians working in diabetes, nephrology, and preventive cardiology may find SAF a useful research-grade biomarker for monitoring lifestyle intervention responses in trial settings. General adult population across the lifespan. Most directly applicable to adults at elevated cardiovascular risk, those with metabolic syndrome, type 2 diabetes, or chronic kidney disease — populations in whom SAF has established prognostic utility. Findings are less directly actionable for healthy low-risk adults where SAF monitoring is not routine clinical practice.
Abstract
INTRODUCTION: Accumulation of advanced glycation end products, measured by skin autofluorescence (SAF), has been shown to be associated with several chronic non-communicable diseases, particularly cardiovascular diseases (CVDs). The promotion of physical activity (PA) as a strategy for the prevention of CVD by modifying healthy habits has been widely studied. AIM: To assess the evidence for the association between PA and SAF in the general adult population. METHODS: A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and the Synthesis Without Meta-analysis framework. A search was performed in MEDLINE (via PubMed), Web of Science, Scopus, Cochrane Library and SportDiscuss (via EBSCOhost), from inception to September 2024. Study quality was assessed using the National Heart, Lung and Blood Institute tools and the certainty of evidence was evaluated with Grading of Recommendations, Assessment Development and Evaluation. Vote counting based on the direction of effect was used as the standardised synthesis metric. RESULTS: In the systematic review, 17 studies were included. The qualitative synthesis showed a predominant consistency in favour of a beneficial association. Specifically, 58.8% of the studies reported a statistically significant inverse association, indicating that higher levels of PA or exercise frequency are correlated with lower SAF levels. The remaining studies (41.2%) reported non-significant results, though several showed favourable trends. No studies reported a positive association between PA and SAF. The quality of the studies was generally fair, and the certainty of evidence low. CONCLUSIONS: PA is inversely associated with SAF. Therefore, while causality cannot be proven, it is hypothesised that PA may reduce SAF and thus have a positive impact on health.
References
- 1.Martínez-García, I., Saz-Lara, A., Pascual-Morena, C., Lever-Megina, C. G., Patiño-Cardona, S., Ribeiro, F., & Cavero-Redondo, I. (2026). Analysis of the potential association between physical activity and skin autofluorescence: a systematic review. Journal of Epidemiology and Community Health. Advance online publication. https://doi.org/10.1136/jech-2025-224810
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