Trajectory-Dependent Systemic Adaptation (TDSA) Model

Abstract This document presents a mathematical hypothesis for systemic biological changes during spaceflight, focusing on reversible dynamics such as telomere length. The model posits a trajectory-dependent biomechano-chemical response, where changes in gravitational acceleration (∇g) act as a primary driver, triggering adaptive cascades via mechanotransduction. Gravity is framed as an inertial compressional load, equivalent in free fall scenarios (e. g. , orbit or accelerating frames like elevators). The equation integrates non-linear adaptation to a new equilibrium, baseline aging, gravitational stress, and radiation damage, providing a unified, testable framework for space medicine. Aligned with NASA Twins Study data, it offers predictions for multi-transition missions like Artemis or Mars voyages, including applications to lunar environments. 1. The Foundational Concept: Gravity as an Inertial Compressional Load Gravity imparts a constant, background compressional load on biological structures through inertial forces, manifesting as weight (mass × g). On Earth (1g), cells and their components experience a static preload due to this mass-dependent force, creating mechanical pre-stress in the cytoskeleton, nuclear matrix, and other structures. This baseline tension is essential for homeostasis, with mechanosensing pathways (e. g. , integrins, YAP/TAZ) converting physical loads into biochemical signals. Entry into microgravity (0g) or equivalent free fall (e. g. , orbital flight or a plummeting elevator) removes this inertial load, leading to a "relaxation" or "loosening" of cellular structures. This perturbation is detected as a primary signal, initiating systemic adaptive responses to re-establish equilibrium. The equivalence of free fall scenarios underscores that the response is driven by the effective absence of weight, not gravity per se, aligning with general relativity's principles and short-term analogs like parabolic flights. This framework explains spaceflight phenomena as an adaptive biomechano-chemical cascade: load changes trigger mechanotransduction, altering gene expression, telomere maintenance, immune function, and more. 2. The Mathematical Model: A Unified Framework The dynamics of a biological state variable S (t) (e. g. , telomere length, gene expression, muscle mass) in response to environmental trajectory changes are described by: lnS_ (t) /S₀ =-alpha-beta. neblag-lamda. R. (1- e^ (-t/T) ) perturbation is detected as a primary signal, initiating systemic adaptive responses to re-establish equilibrium. The equivalence of free fall scenarios underscores that the response is driven by the effective absence of weight, not gravity per sec, aligning with general relativity's principles and short-term analogs like parabolic flight