Exercise-induced irisin-BDNF signaling in aging: implications for cognitive decline, sarcopenia, and neurodegeneration. A narrative review.

Authors

Emine Merve Ersever

Published in

European journal of translational myology. Aug 26, 2026. Epub Aug 26, 2026.

Abstract

Age-related cognitive decline is closely associated with diminished neuroplasticity and disrupted neurotrophic signaling. Exercise is a potent modulator of the irisin-BDNF axis, a molecular pathway with emerging relevance to healthy aging, neuroprotection, and the prevention of neurodegenerative diseases in older adults. Through this analysys the author aimed to review evidence on the effects of different exercise modalities - with emphasis on aging populations - on the PGC-1α-FNDC5-irisin-BDNF signaling pathway, and to examine implications for cognitive health and neuroplastic adaptations across the lifespan. A structured, reproducible search of PubMed, Scopus, Web of Science, and Google Scholar was conducted for studies published between January 1995 and September 2025, using Boolean combinations of 'irisin', 'BDNF', 'exercise', 'aging', 'neuroplasticity', and 'cognitive function'. Human and animal studies exploring the irisin-BDNF axis in the context of aging, physical activity, or immobilization were eligible. Data were extracted and synthesized qualitatively. Consistent with the narrative design, no formal risk-of-bias instrument or PRISMA systematic-review reporting framework was applied, and the review was not prospectively registered. Twenty-four studies met inclusion criteria. Resistance and High-Intensity Interval Training (HIIT) consistently increased circulating irisin and hippocampal BDNF levels. Aging-related declines in both biomarkers were attenuated by chronic resistance training, particularly in older adults. Immobilization suppressed the irisin-BDNF pathway. Epigenetic modifications at BDNF promoters represent a plausible mechanism for sustained neuroplastic adaptations. The PGC-1α-FNDC5-irisin-BDNF axis may constitute a key molecular link between skeletal muscle activity and brain health in aging populations. Resistance training and HIIT offer the most consistent evidence for attenuating age-related neurotrophic decline, although HIIT-specific data in older adults remain limited and warrant cautious interpretation. Causal conclusions remain premature given the predominantly associative and preclinical evidence base. Well-powered, longitudinal prospective trials in older adults with standardized biomarker protocols are needed.

PMID:
42644357
Bibliographic data and abstract were imported from PubMed on 26 Aug 2026.

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