What can 3D mitochondrial structures tell us about aging muscles?

The continued loss of skeletal muscle mass and strength is an undeniable element in aging.^1,2 Once reaching age 40, adults lose around 8 % of their muscle mass per decade. This increases to 15 % per decade following the age of 70 years.¹ This muscle loss, called sarcopenia, is the most significant cause of frailty in the elderly.³ It leads to a significant drop in the quality of life in this age group,⁴ as it is associated with a greater risk of mortality and disability caused by functional impairment, fractures, and falls.^1,2

Image Credit: rasamma/Shutterstock.com

In 2016, sarcopenia was recognized as a disease and given an ICD-10-CM code (M62.84).^3,4 However, the originating causes of sarcopenia are largely unknown and have no clinical treatments at present, with exercise being the only established therapy.^1,3

In recent years, mitochondrial dysfunction has become a possible mechanism that could explain the development of sarcopenia. Transformations in mitochondria function are seen before the loss of muscle mass and function, and experimental evidence in rodents, as well as humans, has resulted in the strong suggestion that a decrease in mitochondrial bioenergetics is the accompaniment to the muscle aging process.^1,2

However, the structural changes and mechanisms in mitochondria that result in this decline of function are not well understood.^1,2 Recently, a study by the team from Vanderbilt University in Nashville, Tennessee, involved a series of experiments to shed light on the structural changes in mitochondria that accompany sarcopenia.

Subcellular discoveries

The team started by studying skeletal muscle in the quadriceps through magnetic resonance imaging in a selection of individuals aged 18-50, who were compared against a group aged 50+. This showed that, in all genders, the muscle volume in the thigh region declines in relation to the bone area throughout aging.

To investigate what may occur at the mitochondrial level to instigate these changes, the team researched the expression of mitochondrial proteins in skeletal muscle samples derived from young (18-50 years) and old (50-90 years) people. This demonstrated that aging comes with a decrease in mitochondrial fusion and fission proteins, as seen in previous studies. These decreases would be expected to impair the structure and dynamics of the mitochondria.

3D visualization

To explore the effect of these transformations on the mitochondrial structure, the team used a serial block face–scanning electron microscope (SBF-SEM) to execute a 3D reconstruction of the mitochondria, utilizing quadriceps samples from individuals over or under 50 years of age.

Using several methods to examine the complexity of the mitochondria, the team discovered that in younger people, mitochondria had elongated structure and greater complexity. Comparatively, mitochondria from older people were typically more compact and spherical. Interestingly, researchers collected various morphometric data, including surface area, perimeter, and volume. No differences in surface area and perimeter were observed between young and old human skeletal muscle. However, mitochondrial volume increased in aged human skeletal muscle, potentially indicating swelling. Additionally, significant alterations in mitochondrial morphology were observed, which may indicate dysfunction and sarcopenia.

Therapeutic potential

Scientists have identified that the decrease of certain mitochondrial proteins, specifically MFN2, is linked to structural changes in skeletal muscle mitochondria, contributing to sarcopenia. Importantly, they found that regular exercise can restore and increase MFN2 protein levels, effectively helping to combat sarcopenia.

The authors suggest that MFN2 could serve as a potential therapy for age-related changes in skeletal muscle mitochondrial structure, indicating a future mechanistic target for addressing exercise-induced muscle atrophy.

This research clarifies the mechanisms by which exercise supports healthy muscle aging, emphasizing its role as an effective therapy.

ThermoFisher technology

The researchers employed SBF-SEM to obtain a comprehensive ultrastructure of the mitochondria. Using the stack alignment and segmentation tools in Amira software, they unveiled the mitochondria's three-dimensional structure. This 3D reconstruction in Amira allowed them to identify mitochondrial morphology and compare the differences between young and old individuals.

Amira Software provides 2D-5D image visualization and processing from various modalities, including CT, MRI, and optical and electron microscopy. Through the power of AI, Amira Software offers advanced features and automation to allow both experts and users with less experience to perform complex analyses and gain insights from the data.

Watch on-demand how to maximize your cell biology images with Amira Software

References and further reading

1. Scudese E, Vue Z, Katti P, et al. 3D Mitochondrial Structure in Aging Human Skeletal Muscle: Insights into MFN-2 Mediated Changes. bioRxiv [Preprint]. 2024 Jun 8:2023.11.13.566502. doi: 10.1101/2023.11.13.566502.
2. Leduc-Gaudet JP, Hussain SNA, Barreiro E, et al. Mitochondrial Dynamics and Mitophagy in Skeletal Muscle Health and Aging. Int J Mol Sci. 2021;22(15):8179. doi: 10.3390/ijms22158179.
3. Anker SD, Morley JE, von Haehling S. Welcome to the ICD-10 code for sarcopenia. J Cachexia Sarcopenia Muscle. 2016;7(5):512-514. doi: 10.1002/jcsm.12147.
4. Sebastián D, Zorzano A. When MFN2 (mitofusin 2) met autophagy: A new age for old muscles. Autophagy. 2016;12(11):2250-2251. doi: 10.1080/15548627.2016.1215383.

Sponsored Content Policy: News-Medical.net publishes articles and related content that may be derived from sources where we have existing commercial relationships, provided such content adds value to the core editorial ethos of News-Medical.Net which is to educate and inform site visitors interested in medical research, science, medical devices and treatments.