Aging is universally accompanied by a decline in cognitive domains such as executive function and memory, but the trajectory of this decline is highly variable. The search for peripheral biomarkers that dictate central nervous system preservation has largely focused on classical neurotrophic factors and inflammatory cytokines. However, recent data highlights the muscle-brain axis, specifically exercise-induced metabolites, as critical mediators of cognitive longevity.
This cross-sectional study investigated the relationship between physical fitness, body composition, systemic inflammation, and circulating neuroproteins with cognitive function in an aging cohort. The most significant finding is the identification of N-lactoyl-phenylalanine (Lac-Phe) as a potential biomarker for cognitive preservation. Lac-Phe, a metabolite formed from lactate and phenylalanine during physical exertion, was significantly associated with enhanced psychomotor speed. Conversely, systemic low-grade inflammation driven by excess adiposity—marked by elevated interleukins (IL-6, IL-8, IL-12) and the neuroprotein clusterin (Clu)—correlated with worsened inhibitory control and memory deficits.
The data reinforces a divergence in tissue-specific aging priorities: adipose tissue accumulation drives neuroinflammation and executive dysfunction, whereas skeletal muscle mass and cardiorespiratory fitness (VO2peak) act as neuroprotective sinks that preserve visuospatial memory. Interestingly, established biomarkers like brain-derived neurotrophic factor (BDNF) and cortisol failed to show significant correlations with cognitive performance in this cohort. The findings strongly suggest that interventions targeting the reduction of visceral fat and the augmentation of muscle-derived metabolites like Lac-Phe could be highly actionable pathways for extending cognitive healthspan.
Context
- Paper: N‑lactoyl‑phenylalanine as a possible biomarkerof cognition? Association between neuroproteins, cytokines,body composition, physical fitness and cognitive functionin older adults
- Institution: Gdansk University of Physical Education and Sport; Medical University of Gdansk.
- Country: Poland.
- Journal: GeroScience.
- Impact Evaluation The impact score of this journal is 5.3, evaluated against a typical high-end range of 0–60+ for top general science, therefore this is a Medium impact journal.