"The Impact of Titin on Muscle Fiber Composition during Aging" by Shannon Wong

Graduation Year

2025

Document Type

Campus Only Senior Thesis

Degree Name

Bachelor of Arts

Department

Human Biology

Reader 1

Jenna Monroy

Reader 2

Suryatapa Jha

Abstract

This study examined muscle fiber composition in the soleus muscles of young and old wild-type and TtnΔ112-158 mice to understand titin's role in age-related changes in muscle structure. Titin, a crucial protein in muscles, serves structural, mechanical, and signaling functions, contributing to muscle elasticity and stiffness. Its mechanosensitive properties regulate muscle growth and adaptation to mechanical stimuli, influencing muscle hypertrophy and function. Muscle aging, marked by sarcopenia, includes a shift toward Type I (slow-twitch) fibers, which are fatigue-resistant but contract slowly, and atrophy of Type II (fast-twitch) fibers, which are powerful but less enduring. I hypothesized that older mice would have a higher proportion of Type I fibers, reflecting typical aging changes, and that TtnΔ112-158 mice would show a more uniform fiber type distribution due to the titin deletion. Muscle samples were analyzed using immunohistochemistry to detect myosin heavy chain (MHC) isoforms in different fiber types. Results showed a non-significant predominance of Type IIa fibers across all groups, contrary to the anticipated age-related shift towards Type I fibers. In wild-type mice, both Type I and Type IIa fibers increased in size with age, while in TtnΔ112-158 mice, Type I fibers decreased and Type IIa fibers increased in size. These findings suggest that reduced titin may influence muscle structural integrity and adaptation to age-related mechanical demands, resulting in a more uniform, but not statistically significant, fiber composition in mutant mice. This study highlights titin’s importance in muscle adaptation and suggests that genetic factors, like titin size, impact age-related muscle composition changes.

This thesis is restricted to the Claremont Colleges current faculty, students, and staff.

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