Study of sarcopenia in skeletal muscle fibers through Raman spectroscopy and chemometrics

• Grant number: 25/16558-8
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: April 01, 2026
• End date: March 31, 2029
• Field of knowledge: Physical Sciences and Mathematics - Physics - Condensed Matter Physics
• Principal Investigator: Anderson Zanardi de Freitas
• Grantee: André Mourão Batista
• Host Institution: Instituto de Pesquisas Energéticas e Nucleares (IPEN). São Paulo , SP, Brazil
• Associated research grant: 23/04564-8 - PHENOTYPIC CHARACTERIZATION BY RAMAN MICROSCOPY, TERS AND SNOM IN SKELETAL MUSCLE FIBERS OF MICE, AP.R

Abstract

Aging is a progressive and multifactorial process that affects several systems of the body, including the musculoskeletal system. Among the most striking changes associated with advancing age is the deterioration of muscle structure and function,which contributes substantially to the loss of mobility, increased functional dependence, and reduced quality of life. From a tissue perspective, aging causes changes in specific types of muscle fibers, especially the most glycolytic fibers, such as type IIx, which are particularly sensitive to aging. However, oxidative fibers (type I) can also suffer deleterious effects later in life. These fibers play distinct and complementary roles in muscle function and are essential for adequate skeletal movement and maintenance of posture. Our research group has recently developed an alternative method for characterizing muscle fibers, utilizing Raman spectroscopy in conjunction with chemometric techniques. This approach represents a breakthrough because it allows for faster and more detailed analysis, with virtually no sample preparation (only tissue fixation). In addition to identifying specific types of muscle fibers, this technology can also reveal chemical signatures specific to a type of muscle fiber that do not depend on the expression of a specific type of heavy myosin. This method can also be useful to evaluate the behavior of muscle fibers in altered situations, such as immobilization, denervation, injury, and aging, the latter being our focus in this proposal. In this sense, the present project aims to utilize Raman microscopy and chemometrics to identify and characterize specific types of skeletal muscle fibers (I, IIa, IIx, and IIb) in mice throughout aging, thereby generating new insights into the condition of sarcopenia. To execute the proposed project, mice (n = 6) at different periods of life (3, 6, 12, and 18months) will be used, with the soleus (oxidative) and extensor digitorum longus (glycolytic) muscles removed, cryoprotected, and kept at -80°C. Subsequently, fixed tissue sections will be used for RAMAN analysis and chemometrics. In parallel, classical identification of muscle fibers will be performed by immunodetection of specific heavy myosins. We will also measure the expression of MuRF1 and Atrogin1, and the tissue localization of collagen and fat deposits using "oil red" staining. This project has the potential to deepen the understanding of the molecular mechanisms involved in aging and also open the possibility of new ways of characterizing skeletal muscle fibers.