The Associative Learning Prediction Error Feedback Loop as Reversible Driving Belt of the Bioenergetics of Longevity

Leukocyte telomere shortening is a useful biomarker of biological and cellular age that occurs at an accelerated rate in anxiety disorders and posttraumatic stress disorder (PTSD). Intriguingly, inhibitory learning — the systematic exposure to noxious stimuli that serves as a basis for many treatments for anxiety, phobia, and PTSD —reduces relative telomeres attrition rates and increases protective telomerase activity in a manner predictive of treatment response. How does inhibitory learning, a behavioral strategy, modulate organismal chromosomal activity? Inhibitory learning may induce repeated mismatch between treatment expectations, intrasession states, and eventual outcome. Nevertheless, inhibitory learning can incentivize repetition of the behavior. Thus, this paper aims to conceptualize inhibitory learning as involving a ‘prediction error feedback loop’, i.e., a series of self-perpetuating prediction errors — mismatches between expectations and outcomes — that enhances neural inhibitory regulation to effectuate extinction. Inhibitory learning is necessarily predicated upon an opposing process – excitatory learning – that may be conceptualized as a prediction error feedback loop that operates in reverse to inhibitory learning and enhances neural excitability as arousal. Together, excitatory and inhibitory learning may be elements of an associative learning prediction error feedback loop responsible for modulating neural bioenergetic rates, leading to changes in downstream cellular signaling that could explain reduced or increased rates of leukocyte telomere shortening and telomerase activity from each behavioral strategy, respectively.