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1. Cellular & Molecular Mechanisms of Cardiac Aging Aging is a process whereby progressive decline of tissue homeostasis reduces system function and elevates risk of death. Age itself is a major risk factor for a range of human diseases, such as cancer, diabetes, neurodegeneration and heart disease. Specifically, aging is associated with an 8-fold increase of the incidence of sudden cardiac death (SCD), the leading cause of death in western countries. Resolving the contributing mechanisms of heart disease in any of its forms is a pressing goal of basic and translational aging research.
We have recently identified Activin signaling, a member of the TGF-beta superfamily, as a regulator for longevity and autophagy of flight muscle in Drosophila. Very little is known whether and how Activin signaling might influence cardiomyopathy or its progression with age. In this project, we will investigate how Activin signaling regulates autophagy and proteostasis in aging cardiac muscle. We aim to address two fundamental questions:
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Immunostaining of insulin-like peptides (DILP2 and DILP5) in flies with fat body-specific Dilp6 expression
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2. Inter-Organ Communication via Systemic Signals
The tissue-specific roles of known longevity pathways in the regulation of lifespan have been reported from several studies. However, it is unclear how genetic manipulation of these pathways within certain tissue can result in a systemic effect on organism’s fitness and survival. It has been proposed that secretory signal molecules are the mediators for such systemic effects. In the past decade, skeletal muscle has been recognized as a key endocrine organ that can produce and release myokines (muscle-derived hormonal factors) for the communication between muscle and other organs (e.g. adipose tissue, pancreas and brain).
Recent studies from our laboratory and others have shown that there is a strong connection between muscle function and organismal aging. Muscle functions and muscle protein homeostasis decline with age, whereas well-preserved muscle homeostasis leads to improved organism-wide performance, altered systemic insulin/IGF signal (IIS) and extended lifespan. In this project, we aim to identify a set of myokines, which are the downstream targets of longevity assurance pathways, are mediating inter-tissue communication and involved in the regulation of lifespan and health-span. |
Activin signaling-mediated autophagosome formation (indicated by Atg8a puncta) in flight muscle
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3. Stress and Tissue Homeostasis
Over the past few years, my research interests have focused on autophagy/lysosome, protein homeostasis and their roles in muscle aging. Autophagy/lysosome system provides proteolytic mechanisms to regulate protein turnover and degradation. Accumulated evidence suggests that the effective removal of protein aggregates and damaged mitochondria via autophagy contributes to the crucial mechanism for the maintenance of tissue homeostasis and tissue functions. In this project, we aim to elucidate the genetic and molecular pathways that modulate autophagy/lysosome system, especially in the context of stress conditions (e.g. elevated temperature, environmental toxins, imbalance diet, or sleep deprivation).
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