Bioengineered skeletal muscle as a model of muscle aging and regeneration

Nika Rajabian

Nika Rajabian presenting her research at a poster presentation.

Nika Rajabian presenting her research at a poster presentation.

Graduate Student Project

Introduction

Do you know about the aging and how it effects on skeletal muscle?

My name is Nika Rajabian, a PhD candidate in the Department of Chemical and Biological Engineering. I conducted my research in tissue engineering lab under Dr. Andreadis as my mentor. I am working on a senescent model of bioengineered skeletal muscle that can be used to investigate the biological impact of aging on metabolic or genetic diseases.

Skeletal muscle comprises 45-55% of body mass and plays important physiological roles in the body, such as enabling skeletal movements and regulating metabolism. One of the major medical problems facing the elderly is the loss of muscle mass and force-generating capacity, which is known as sarcopenia. I developed  a 3D model of skeletal muscle tissue to study the effects of stem cell senescence (aging) on tissue function and how reversing the stem cell senescence may restore it. The in vitro 3D bioengineered senescent skeletal muscle tissue using primary human myoblasts exhibited significantly reduced ability to generate contractile force and to regenerate in response to injury, similar to in vivo skeletal muscle from aged individuals. Therefore, my work may provide a powerful model for studying aging. In particular, it can be a platform for genetic or pharmacological testing to facilitate drug discoveries to lessen the impact of sarcopenia and restore muscle function.

Abstract

With age, adult skeletal muscle (SkM) is known to decrease in muscle mass, strength and functional capacity, a state known as sarcopenia. Here we developed an in vitro three-dimensional (3D) bioengineered senescent skeletal muscle (SkM) tissue using primary human myoblasts. These tissues exhibited the characteristics of atrophied muscle, including expression of senescent genes, decreased number of satellite cells, reduced number and size of myofibers and compromised metabolism and calcium flux. As a result, senescent SkM tissues showed impaired ability to generate force in response to electrical stimulation as compared to young tissues. Furthermore, in contrast to young SkM tissues, senescent tissues failed to regenerate in response to injury, possibly as a result of persistent apoptosis and failure to initiate a proliferation program. Our findings suggest that 3D senescent SkM may provide a powerful model for studying aging and a platform for drug testing and discovery of therapeutic compounds to improve the function of sarcopenic muscle. Do you know about the aging and how it effects on skeletal muscle?

My name is Nika Rajabian, a PhD candidate in the Department of Chemical and Biological Engineering. I conducted my research in tissue engineering lab under Dr. Andreadis as my mentor. I am working on a senescent model of bioengineered skeletal muscle that can be used to investigate the biological impact of aging on metabolic or genetic diseases.

Skeletal muscle comprises 45-55% of body mass and plays important physiological roles in the body, such as enabling skeletal movements and regulating metabolism. One of the major medical problems facing the elderly is the loss of muscle mass and force-generating capacity, which is known as sarcopenia. I developed  a 3D model of skeletal muscle tissue to study the effects of stem cell senescence (aging) on tissue function and how reversing the stem cell senescence may restore it. The in vitro 3D bioengineered senescent skeletal muscle tissue using primary human myoblasts exhibited significantly reduced ability to generate contractile force and to regenerate in response to injury, similar to in vivo skeletal muscle from aged individuals. Therefore, my work may provide a powerful model for studying aging. In particular, it can be a platform for genetic or pharmacological testing to facilitate drug discoveries to lessen the impact of sarcopenia and restore muscle function.

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