Aging as a Loss of Goal-Directedness: An Evolutionary Simulation and Analysis Unifying Regeneration with Anatomical Rejuvenation

Aging is an extensive biological process characterized by morphological and functional alterations in cellular and extracellular components, resulting in a systematic decline in biological functions ultimately leading to death. Although substantial advancements have been made in manipulating lifespan in model organisms like C. elegans and mice through genetic, dietary, and pharmacological means, the fundamental mechanisms driving aging in humans remain elusive and widely debated. In addition, there is no comprehensive computational platform capable of making predictions on aging in multicellular systems and integrating the multiscale competency of lifeforms. We focus on the processes that build and maintain a complex anatomy toward a specific target morphology, and propose the hypothesis that aging arises even in the absence of accumulated cellular or genetic damage, because a homeodynamic system left without any goal in anatomical morphospace will start degrading. This can occur in biological systems because evolution typically prioritizes development over morphostasis, leaving organisms with limited reinforcement of anatomical goals after development. Using an in silico model of homeostatic morphogenesis with a multiscale competency architecture and information dynamics analysis, we find: (1) Absence of Long-Term Morphostasis: Aging emerges naturally after development due to the lack of an evolved regenerative goal, rather than just specific detrimental properties of developmental programs (e.g., antagonistic pleiotropy or hyperfunction); (2) Acceleration Factors vs. Root Cause: Cellular misdifferentiation, reduced competency, communication failures, and genetic damage all accelerate aging but are not its primary cause; (3) Information Dynamics in Aging: Aging correlates with increased active information storage and transfer entropy, while spatial entropy measures distinguish two dynamics—loss of structure and morphological noise accumulation; (4) Dormant Regenerative Potential: Despite organ loss, spatial information persists in the cybernetic tissue, indicating a memory of lost structures, which can be reactivated for organ restoration through targeted regenerative information; and (5) Optimized Regeneration Strategies: Restoration is most efficient when regenerative information includes differential patterns of affected cells and their neighboring tissue, highlighting strategies for rejuvenation. These findings provide a novel perspective on aging dynamics with significant implications for longevity research and regenerative medicine.