How the BDNF Pathway Changes with Age

Brain-derived neurotrophic factor (BDNF) is a secreted neurotrophic protein of the neurotrophin family, acting through the tropomyosin receptor kinase B (TrkB) receptor and the p75 neurotrophin receptor. It is the principal ligand in the BDNF-TrkB signalling axis, the pathway most frequently implicated in activity-dependent neuroplasticity. The evidence reviewed here does not supply a sequence, molecular formula or molecular weight for BDNF, and none is asserted.

The work summarised below centres on the BDNF pathway as it intersects with the muscle-brain axis — the signalling route by which skeletal muscle communicates with the ageing central nervous system — and on the irisin-BDNF axis as a modulator of neurotrophic signalling in older adults [1][2].

Research Studies

BDNF and the muscle-brain axis in ageing

A narrative review synthesised mechanistic and translational evidence on how skeletal muscle communicates with the ageing brain through myokines and exerkines, and how progressive sarcopenia disrupts that signalling to accelerate cognitive impairment [1]. BDNF was named among the mediators examined, 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 review's framing is that sarcopenia and cognitive decline frequently co-occur in older adults and appear to share a common biological substrate centred on the muscle-brain axis [1].

BDNF and irisin-BDNF signalling in older adults

A second narrative review reported that age-related cognitive decline is closely associated with diminished neuroplasticity and disrupted neurotrophic signalling, and that exercise is a potent modulator of the irisin-BDNF axis [2]. That axis was described as having emerging relevance to healthy ageing, neuroprotection and the prevention of neurodegenerative disease in older adults [2]. This source is reference-only material and is reported here as background rather than as the basis of a dedicated section.

BDNF and the mediators compared across the muscle-brain axis

The mediators named in the muscle-brain axis review are set out below as the review presented them. The table records which mediators the review named; it does not record effect sizes, because the evidence block does not supply them.

BDNF and sarcopenia as a shared substrate

The muscle-brain axis review treated sarcopenia and cognitive decline as conditions that frequently co-occur in older adults, and proposed a shared biological substrate rather than two independent processes [1]. Within that model, progressive loss of skeletal muscle mass disrupts myokine and exerkine signalling, and BDNF is one of the signalling components carried in that disrupted traffic [1].

BDNF and exercise as a modulator of the axis

The irisin-BDNF review characterised exercise as a potent modulator of the irisin-BDNF axis in the context of ageing [2]. The same review linked age-related cognitive decline to diminished neuroplasticity and disrupted neurotrophic signalling [2]. No exercise protocol, intensity, duration or measured BDNF change is given in the evidence block, and none is stated here.

BDNF and neuroprotection in older adults

The irisin-BDNF axis was described as having emerging relevance to neuroprotection and to the prevention of neurodegenerative disease specifically in older adults [2]. The word used in that source is emerging; the evidence block does not contain a trial result, a biomarker threshold or a clinical endpoint supporting a stronger claim.

BDNF and the limits of the current evidence

Both sources in the evidence block are narrative reviews rather than primary experimental reports [1][2]. The evidence block does not specify whether the underlying findings were obtained in animal models, in vitro preparations or human cohorts, and it does not supply species, sample sizes or effect estimates. Where the evidence block is silent on model system, this page is silent too.

BDNF and what the reviews do not establish

Neither review, as represented in the evidence block, reports a dose, a threshold, a time course or a direction of change in BDNF concentration with age [1][2]. The muscle-brain axis review describes a mechanistic framework linking sarcopenia to cognitive decline and discusses implications for preventive strategies in ageing [1]. The irisin-BDNF review describes a pathway with emerging relevance to healthy ageing [2]. Neither is presented here as establishing causation.

If you are reading this for personal health reasons

The materials described on this page are sold for laboratory research use only, and we do not provide dosing information or medical guidance of any kind. Nothing here is a recommendation to take any compound, and no outcome is promised or implied. Anyone considering a compound for themselves should speak to a licensed clinician.

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/