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Mitochondrial Dysfunction

Linking Type 1 Diabetes and Sarcopenia

Alway, Stephen E.

Exercise and Sport Sciences Reviews: April 2019 - Volume 47 - Issue 2 - p 63
doi: 10.1249/JES.0000000000000186
Commentaries to Accompany

Laboratory of Muscle Biology and Sarcopenia Department of Physical Therapy University of Tennessee Health College of Health Professions and Department of Physiology, College of Medicine University of Tennessee Health Science Center College of Medicine, Memphis, TN

Authors for this section are recruited by Commentary Editor: Russell R. Pate, Ph.D., FACSM, Department of Exercise Science, University of South Carolina, Columbia, SC 29208 (E-mail:

The loss of insulin production by the β-cells in the pancreas leads to type 1 diabetes mellitus (T1D). Although adding exogenous insulin is the primary strategy for treating T1D, it does not cure the disease, resulting in a deterioration of muscle function and the quality of life in persons with T1D. In the current issue of Exercise and Sport Sciences Reviews, Monaco et al. (1) propose a novel hypothesis that the loss of muscle function and mass in T1D is really an accelerated form of the aging-associated decrease of muscle strength and mass, which we call sarcopenia. Although sarcopenia begins slowly and occurs over several decades, Monaco et al. (1) argue that muscle dysfunction occurs more rapidly in T1D than normal aging, and this metabolic disease results in a sarcopenic-like phenotype that is seen in young persons with T1D.

These investigators (1) propose that mitochondrial dysfunction is the common link that regulates muscle deterioration in both aging and T1D. In their model (1), loss of mitochondrial function in T1D (2,3) is similar to that which occurs in aging (4). The similarities in mitochondrial dysfunction between T1D and sarcopenia are striking and include increased mitochondrial reactive oxygen species production/elevated oxidative stress, reduced mitochondrial respiration and oxidative capacity, and increased opening of the mitochondrial permeability pore that leads to mitochondrial-induced signaling for cell death including apoptosis (3,5). However, muscle loss occurs more rapidly in T1D, providing an aging-like muscle phenotype at young ages (6). This consists of a loss of muscle mass and strength, as well as metabolic dysregulation in T1D all of which parallels an aged phenotype.

Exercise is the most effective intervention to slow sarcopenia in aging. Exercise may provide similar improvements in muscles from T1D persons by increasing mitochondrial biogenesis and removing damaged mitochondria via mitophagy. If T1D muscles are like elderly muscles, exercise prescription for persons with T1D cannot be simply mirror images of nondiseased and age-matched populations. Rather, exercise prescription should be planned carefully and should include resistance exercise to maintain or improve muscle mass for persons with T1D, in the same way that resistance training is used for elderly subjects to minimize or slow the manifestation of sarcopenia.

If T1D is shown to be an accelerated form of muscle aging, and if mitochondrial dysfunction is the primary culprit in regulating muscle losses as predicted (1), the importance of this paper will be to advance the mitochondria hypothesis as a means to explain the uniqueness of disease progression and as a point for identifying potential molecular targets in mitochondria for intervention in T1D muscle. Furthermore, the paper should provide a catalyst for future investigations toward treatments for T1D that include not only insulin injection/insulin pump but also properly prescribed and delivered exercise (volume, frequency, etc.), in a manner which takes advantage of what we know about exercise for the elderly. Specifically, the exercise intervention should be designed in a fashion that enhances muscle protein accumulation (to reduce the effects of T1D-induced muscle wasting) and improves mitochondrial health.

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1. Monaco CMF, Gingrich MA, Hawke TJ. Considering type 1 diabetes as a form of accelerated muscle aging. Exerc. Sport Sci. Rev. 2019; 47(2):98–107.
2. Baseler WA, Dabkowski ER, Williamson CL, et al. Proteomic alterations of distinct mitochondrial subpopulations in the type 1 diabetic heart: contribution of protein import dysfunction. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2011; 300(2):R186–200.
3. Monaco CMF, Hughes MC, Ramos SV, et al. Altered mitochondrial bioenergetics and ultrastructure in the skeletal muscle of young adults with type 1 diabetes. Diabetologia. 2018; 61(6):1411–23.
4. Alway SE, Mohamed JS, Myers MJ. Mitochondria initiate and regulate sarcopenia. Exerc. Sport Sci. Rev. 2017; 45(2):58–69.
5. Pottecher J, Adamopoulos C, Lejay A, et al. Diabetes worsens skeletal muscle mitochondrial function, oxidative stress, and apoptosis after lower-limb ischemia-reperfusion: implication of the RISK and SAFE pathways? Front. Physiol. 2018; 9:579.
6. Krause MP, Riddell MC, Hawke TJ. Effects of type 1 diabetes mellitus on skeletal muscle: clinical observations and physiological mechanisms. Pediatr. Diabetes. 2011; 12(4 Pt 1):345–64.
© 2019 American College of Sports Medicine