Non-Equilibrium Thermodynamics and Entropy Regulation in Living Systems

Abstract

This thesis explores the fundamental role of entropy production and entropy export as constructive properties of complex living systems, thus arguing for a paradigm shift in how we view biological systems through the lens of the Second Law of Thermodynamics. Our investigation is driven by the hypothesis that non-equilibrium thermodynamics can provide insights in understanding the physiological adaptability and resilience of the human body. The rationale is that complex living systems, such as humans, are characterized by self-organized and dissipative behaviors, necessitating the continuous internal production of entropy and its subsequent export to the environment.

Addressing directly the lack of empirical work in the application of entropy principles to humans, we first build the methodological foundation by introducing an experimental approach for the continuous measurement of entropy production and export in humans exercising under heat stress. We develop a two-compartment entropy flow model and, leveraging existing calorimetric data in humans, detail the use of direct and indirect calorimetry to quantify internal metabolic heat production (related to entropy production) and external heat dissipation (related to entropy export). Most importantly, we provide a thorough discussion on the challenges associated with the measurement of entropy rates in humans, both from a technical and conceptual perspective.

Building upon our validated methodology, we explore the biophysical, physiological and clinical relevance of entropy flow regulation in humans exercising under heat stress. By analyzing retrospective calorimetry data on heat fluxes and body temperature, we investigate how the rates of entropy production, export and overall accumulation are affected by key physiological factors such as age, fitness-level and the presence of a chronic disease (type-2 diabetes). We uncover significant impairments in entropy export, leading to increased entropy accumulation, in association with increased age, decreased fitness level, and the presence of a chronic disease (type-2 diabetes). Our findings suggest that the balance of entropy production and export is a critical factor in maintaining physiological stability and can serve as a potential indicator of health status, while potentially allowing the development of the novel therapeutic approaches in clinical settings.

Finally, we explore the underlying mechanisms of entropy dynamics by introducing a new stochastic model of entropy regulation in humans. Our model, which posits that the entropy export rate is dynamically adjusted in the body in response to the rate of internal entropy accumulation, is represented by a stochastic differential equation that coincidently has the form of a Ornstein-Uhlenbeck process for humans in a resting state, and a time-driven Ornstein-Uhlenbeck process in the regime of alternating periods of exercise and recovery. By fitting our model to the experimental data for young, middle-aged and older participants, we quantify the state-dependent adaptation coefficients (i.e. the ability to respond quickly to a perturbation) and the stochasticity (i.e. noise strength) in the entropy export responses. Our approach thus provides a mechanistic framework for interpreting the dynamic interplay between entropy production and export.

This thesis provides crucial experimental and modeling steps towards a rigorous integration of non-equilibrium thermodynamics into human physiology and health. By establishing experimental feasibility, providing compelling empirical support for the physiological and clinical relevance of entropy balance, and proposing a quantitative modeling framework for entropy regulation, this work contributes to bridging the long-standing gap between fundamental physics and practical applications in human health.