Date of Defense

4-20-2023

Date of Graduation

4-2023

Department

Biological Sciences

First Advisor

John Spitsbergen

Second Advisor

John Geiser

Abstract

By 2060, the average life expectancy in the United State is projected to be above 85. With a fourth of the population expected to be of retirement age, these estimates prompt further consideration of how humans can live not only live longer, but healthier, higher quality lives. In the population, no person is immune to the effects of aging. Within in our neuromuscular system, there is an age-related atrophy of skeletal muscle fibers resulting from a reduced connection with their innervating neurons. This is termed sarcopenia. It leads to increased risks of injury, reduced quality of life, and a subsequent strain on the national healthcare system. One potential candidate to combat sarcopenia is Glial Cell Line-Derived Neurotrophic Factor (GDNF). This protein is produced by skeletal muscle and maintains the health of the Neuromuscular Junction and innervating motor neuron. Exogenous GDNF is challenging to deliver; however, exercise has been shown to increase GDNF and thus promote neuromuscular health with a reduction in the rate of sarcopenia. Muscles composed of Type I, Type IIa, and Type IIb are affected differently by aging. Likewise, exercise effects GDNF production differently across fiber type. Most human muscles have a mix of the three fiber types, but past studies of exercise and GDNF have generalized Type I and Type IIb fibers to whole muscles. Therefore, it is currently unclear how GDNF in muscles of a mixed composition is affected by exercise and aging. There is also less detail about the longitudinal changes in GDNF throughout the entire lifespan. The aim of this study was to bridge these gaps by monitoring the changes in GDNF with aging alongside how exercise may differently affect primarily fast, slow and mixed fiber type muscles. This was tested by using the fast-type Plantaris, slow-type Soleus, and mixed-type Gastrocnemius of 1-month to 24-month-old Sprague Dawley rats. Rats were equally divided into a sedentary or voluntary exercise group (n=6). Enzyme Linked Immunosorbent Assay (ELISA) was used to find GDNF protein concentration in each muscle. Immunohistochemistry was performed to observe fiber-type in the Gastroc. The results of this study indicate that in adult and late adult ages, exercise significantly increased [GDNF] when compared to sedentary age-matched counterparts in all muscles. Exercise had the greatest influence on [GDNF] in the fast-type Plantaris by relatively increasing [GDNF] at 12, 18, and 24-months. In the mixed-type Gastroc, exercise significantly increased GDNF at 12 and 18 months displaying a trend intermediate to the fast and slow type muscles. This indicates that in muscles of a mixed composition, exercise likely effects GDNF in an intermediate fashion. Overall, this study shows how exercise effects different types of skeletal muscle and offers a potential preventative mechanism to combat sarcopenia through its ability to increase GDNF and promote neuromuscular health with aging.

Access Setting

Honors Thesis-Restricted

Restricted to Campus until

6-20-2024

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