PT  - JOURNAL ARTICLE
AU  - Acun, Aylin
AU  - Nguyen, Trung Dung
AU  - Zorlutuna, Pinar
TI  - An aged human heart tissue model showing age-related molecular and functional deterioration resembling the native heart
AID  - 10.1101/287334
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 287334
4099  - http://biorxiv.org/content/early/2018/03/22/287334.short
4100  - http://biorxiv.org/content/early/2018/03/22/287334.full
AB  - 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.