Search bioRxiv⌕ Search

Biology subjects

Acun, A.

Publications and source records attributed to Acun, A..

2 recordsLinked to original sources
bioRxiv2018

An aged human heart tissue model showing age-related molecular and functional deterioration resembling the native heart

Deaths attributed to ischemic heart disease increased by 41.7% from 1990 to 2013. This is primarily due to an increase in the aged population, however, research on cardiovascular disease (CVD) has been overlooking aging, a well-documented contributor to CVD. The field heavily depends on the use of young animals due to lower costs and ready availability, despite the prominent differences between young and aged heart structure and function. Here we present the first human induced pluripotent stem cell (hiPSC)-derived cardiomyocyte (iCM)-based, in vitro aged myocardial tissue model as an alternative research platform. Within 4 months, iCMs go through accelerated senescence and show cellular characteristics of aging. Furthermore, the model tissues fabricated using these aged iCMs, with stiffness resembling that of aged human heart, show functional and pharmacological deterioration specific to aged myocardium. Our novel tissue model with age-appropriate physiology and pathology presents a promising new platform for investigating CVD or other age-related diseases.

bioengineering↗
bioRxiv2017

Interdependence Theory of Tissue Failure: Bulk and Boundary Effects

The mortality rate of many complex multicellular organisms increase with age, which suggests that net aging damage is accumulative, despite remodeling processes. But how exactly do little mishaps in the cellular level accumulate and spread to become a systemic catastrophe? To address this question we present experiments with synthetic tissues, an analytical model consistent with experiments, and a number of implications that follow the analytical model. Our theoretical framework describes how shape, curvature and density influences the propagation of failure in a tissue subject to oxidative damage. We propose that aging is an emergent property governed by interaction between cells, and that intercellular processes play a role that are at least as important as intracellular ones.

biophysics↗