Quantifying geroelasticity through transcriptomic aging clocks during infectious stress

Abstract

This dissertation advances the perspective that aging is dynamic and reversible rather than strictly unidirectional. Biologically meaningful age (or transcriptomic age) is measured here using RNA sequencing data from whole blood of human individuals. Transcriptomic age is far more flexible than chronological age, as shown by reversible age shifts observed during infection. To establish the primary objective of managing aging within theoretical multiomic domains, this work reconceptualizes the reversibility of aging by introducing two new terms: geroelasticity, which draws biophysical analogies from elasticity and plasticity to describe the adaptive properties of multiomic aging against stress, and gerostasis, which models aging as an information-driven process in which entropy accumulation can be computationally minimized and actively maintained via multiomic control. In summary, this dissertation reframes aging as a modifiable process, offering both methodological and conceptual foundations for future research aimed at extending both healthspan and lifespan.