How does the BDNF pathway work?

Brain-derived neurotrophic factor (BDNF) is the formal name of the protein; it is also written as brain derived neurotrophic factor and abbreviated BDNF. It belongs to the neurotrophin class of secreted growth factors, a family that also includes nerve growth factor, neurotrophin-3 and neurotrophin-4. The evidence block supplied for this page does not give a sequence, molecular formula or molecular weight for BDNF, so none is stated here. In the ageing literature BDNF is treated as one of the myokines and exerkines through which skeletal muscle communicates with the brain, alongside irisin/FNDC5, interleukin-6 (IL-6), insulin-like growth factor-1 (IGF-1), cathepsin B and growth differentiation factor-15 (GDF-15) [1].

The pathway centres on the tropomyosin receptor kinase (TrkB) family of receptor tyrosine kinases, which bind neurotrophins and transduce their signals; BDNF is the canonical ligand for TrkB, and the irisin-BDNF axis is the signalling route most often described in the exercise-and-ageing literature [2].

Research Studies

BDNF and the muscle-brain axis in sarcopenia and cognitive decline

A narrative review synthesising mechanistic and translational evidence described the muscle-brain axis as a shared biological substrate linking sarcopenia and cognitive decline in older adults. In that framing, skeletal muscle releases myokines and exerkines — BDNF among them — that act on the ageing brain, and progressive sarcopenia disrupts this signalling in a way that is proposed to accelerate cognitive impairment. The review drew on database searches of PubMed and Scopus, and it treats BDNF as one component of a multi-mediator system rather than as a single causal factor [1].

Irisin-BDNF signalling and neuroplasticity in ageing

A second narrative review reported that age-related cognitive decline is closely associated with diminished neuroplasticity and disrupted neurotrophic signalling, and that exercise acts as a modulator of the irisin-BDNF axis. That axis was described as having emerging relevance to healthy ageing, neuroprotection and the prevention of neurodegenerative disease in older adults [2]. The work is a review of existing literature rather than a primary experimental study, and the population in which the association is described is older adults.

BDNF compared with other myokines in the muscle-brain axis

The mediators discussed across the two reviews differ in how directly they are tied to neural tissue. The table below sets out what each source attributes to each mediator; it is a comparison of how the literature frames them, not a comparison of measured potencies.

Exercise as the modulator of the irisin-BDNF axis

Both reviews place physical exercise upstream of the pathway. The muscle-brain axis review treats muscle contraction as the event that releases myokines and exerkines into circulation, with BDNF among the released factors [1]. The irisin-BDNF review states directly that exercise is a potent modulator of the irisin-BDNF axis and links that modulation to neuroprotection and prevention of neurodegenerative disease in older adults [2]. Neither source, as summarised in the evidence block, reports a dose, a training protocol or a measured change in BDNF concentration.

Where the evidence is animal-only or in vitro

The evidence supplied for this page does not separate its findings by experimental system. Both sources are narrative reviews, and the evidence block does not state which of the mechanistic claims rest on animal models, which on cell culture, and which on human observational data. Where a claim cannot be attributed to a named species or preparation from the evidence given, it is not asserted here. Readers should treat the mechanistic statements above as review-level synthesis rather than as findings from a specified model.

Population in which the associations were observed

The population named in both sources is older adults. The muscle-brain axis review frames sarcopenia and cognitive decline as conditions that frequently co-occur in older adults and that share a common biological substrate [1]. The irisin-BDNF review frames its conclusions around healthy ageing, neuroprotection and neurodegenerative disease prevention in older adults [2]. No paediatric, clinical-trial or non-ageing population is described in the evidence block.

What the evidence does not establish

Neither source, as given, provides quantitative values — no concentrations, no effect sizes, no receptor binding affinities, no time courses. The evidence block also does not identify a specific BDNF assay, isoform, or TrkB splice variant. Claims about direction of effect in humans, about whether raising BDNF changes cognitive outcomes, or about any threshold value are outside what these sources support and are therefore omitted.

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Sources

• [1] Myokines as molecular mediators of the muscle-brain axis: Mechanisms linking sarcopenia to cognitive decline and implications for preventive strategies in ageing — A narrative review. https://pubmed.ncbi.nlm.nih.gov/42520997/
• [2] Exercise-induced irisin-BDNF signaling in aging: implications for cognitive decline, sarcopenia, and neurodegeneration. A narrative review. https://pubmed.ncbi.nlm.nih.gov/42644357/