What You Need to Know about Cellular Health to Prevent Muscle Aging

Posted on Mon, 28 Jan 2019  Comments: 1

By Davide D’Amico, Ph.D., Scientist at Amazentis courtesty of abouturolithina.com

Thirty to forty percent of the total mass of a human body, on average, is skeletal muscle (1). It’s the most abundant tissue. Muscle function is critical not only for locomotion, but also for breathing and other critical body functions. As we age muscle mass and function declines and this starts within our cells. Let’s understand how aging affects cellular health and how to improve it to age better.

Muscle aging can culminate with sarcopenia, a medical condition that represents the extreme of muscle loss with aging, whereby individuals suffer from a loss of muscle mass and accompanying muscle weakness (2). This can make daily activities as basic as going up stairs or getting up from a chair difficult. While this is most frequent in older individuals, the first signs of muscle aging appear earlier than you might think, already starting during our 30s.

Cells are the building blocks of our muscles and numerous biological processes control cellular health, some of which decline over time and prime muscle aging. Several key underlying factors of muscle cell aging include mitochondrial function, protein quality control, oxidative status, muscle cell renewal, insulin sensitivity and circulation factors.

Research Program - Energy, Endurance & Stamina

Key regulators of cellular health

1. Mitochondria: Mitochondria are the organelles found inside our cells that produce the required energy (ATP) for cellular function. Mitochondrial health inevitably declines over time and is affected by several diseases and lifestyle factors (3). Old mitochondria have reduced respiratory capacity, which means they are less able to produce energy in the form of ATP molecules. Also, they tend to produce more toxic metabolites (3). Mitochondria are dynamic organelles and cells can build up new, healthier mitochondria in a process called mitochondrial biogenesis. These mitochondria get interconnected in mitochondrial networks to optimize their functioning and when they are exhausted or damaged, are broken down in smaller organelles and selectively removed through a process called mitophagy (4). Healthy muscles require that these mitochondrial dynamics are always well functioning (5). A deficit in mitochondrial biogenesis and mitophagy are well-known hallmarks of aging (6) and cause abnormalities in mitochondria number, morphology and function. As a consequence, mitochondrial dysfunctions all lead to a loss of muscle mass.

2. Protein quality and autophagy: Damaged or aggregated protein inside our cells leads to cellular stress. Indeed, protein homeostasis (or proteostasis), the natural process of controlling the production and removal of proteins in cells, is crucial to maintaining healthy cells (7). Cells recognize and fix misfolded or damaged proteins and when there is no way to repair them, they get rid of them. Cells have their own cleaning system and they can remove proteins as well as other damaged cell structures by a process called autophagy. Mitophagy, that we discussed above, is indeed the specific autophagy of mitochondria. When proteostasis and autophagy don’t work properly, and this is the case upon aging, cells accumulate damaged elements. Over time, this intracellular garbage can become toxic, damage our cells and cause the reduction of muscle size and function.

3. Oxidative status: Metabolic reactions can generate byproducts called ROS, which stands for “reactive oxygen species”. While low levels of ROS have normal physiological functions, an excess of these molecules becomes detrimental, since they can easily react with and damage proteins, lipids, and DNA (6). Oxidative stress is often the prelude to tissue inflammation, another key feature of muscle aging. Of note, dysfunctional mitochondria are a major source of ROS and oxidative stress.

4. Regenerative ability: The large majority of our skeletal muscle cells, which make up muscle tissue, are mature and do not divide anymore, meaning they cannot regenerate the tissue. However, the muscles host a small number of stem cells – which keep the ability to reproduce and are also called “satellite cells”. They are responsible for the growth and repair of muscle tissue. Research has demonstrated that the ability of these muscle stem cells to repair does not decrease over time. However, aging clearly reduces the number of stem cells and, therefore, has an impact on the body’s capacity to grow and repair muscle (8).

5. Insulin sensitivity: muscle cells respond to insulin thereby contributing to the uptake of blood glucose. However, upon aging, muscle cells become resistant to insulin with a negative effect on energy metabolism (9).

6. Circulating factors: Hormones and growth factors that circulate in the blood have an effect on nearby tissues as well as on distant organs. Myokines are small proteins produced by muscle cells and released into the blood when muscles contract. They can act locally on the nearby muscle and immune cells or have effects in distant organs (such as the brain). Myokines can play an important role in muscle maintenance, or trigger muscle fiber swelling after exercise. However, myokines tend to decrease with age (10).

Conclusion

Muscle aging is a complex process, but science is starting to understand how it works. Having a sense of how cellular health declines with aging is important to define effective prevention and interventional strategies. So far, we know that two lifestyle changes can combat muscle aging: regular exercise and optimal nutrition. However, this does not mean merely abiding by the classic “five fruits and veggies a day” rule, but refers to smart nutrition, tailored to impact these key biological processes described above that impact muscle health with age.

References

  1. Janssen, I., et al. Skeletal muscle mass and distribution in 468 men and women aged 18–88 yr. J. Appl. Physiol., 89, 81–88 (2000).
  2. Beaudart, C., et al. Sarcopenia: burden and challenges for public health. Arch. Public Health, 72, (2014).
  3. Youle, R. J. & Narendra, D. P. Mechanisms of mitophagy. Nat. Rev. Mol. Cell Biol., 12, 9–14 (2011).
  4. Sun, N., et al. The Mitochondrial Basis of Aging. Mol. Cell, 61, 654–666 (2016).
  5. Ploumi, C., et al. Mitochondrial biogenesis and clearance: a balancing act. FEBS J., 284, 183–195 (2017).
  6. López-Otín, C., et al. The Hallmarks of Aging. Cell, 153, 1194–1217 (2013).
  7. Klaips, C. L., et al. Pathways of cellular proteostasis in aging and disease. J. Cell Biol., 217, 51–63 (2018).
  8. Hwang, A. B. & Brack, A. S. Muscle Stem Cells and Aging. Curr. Top. Dev. Biol., 126, 299–322 (2018).
  9. Distefano, G. & Goodpaster, B. H. Effects of Exercise and Aging on Skeletal Muscle. Cold Spring Harb. Perspect. Med., 8, a029785 (2018).
  10. Schnyder, S. & Handschin, C. Skeletal muscle as an endocrine organ: PGC-1α, myokines and exercise. Bone, 80, 115–125 (2015).

Published with permission from Amazentis SA

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Comments

  • Eileen Harrison

    By Eileen Harrison Thu, 14 Feb 2019

    KGK MUSCLE MASS STUDY - Comments from a Participant!

    Ever since I was accepted last December, 2018 for the KGK Science, London, Ontario study regarding the loss of muscle mass or density, with age, I have done a lot of research on this issue, not only for myself, but for older friends and family. I am particularly interested in how this affects women after menopause. The staff at KGK are amazing to work with, as was the Surgeon who did the muscle biopsy!

    I’ve learned that people who are physically inactive can lose between 3 – 5 % of their muscle mass, each decade after the age of 30. This is apparently caused by age-related sarcopenia. This is scary, as that means people lose their strength, endurance and mobility over time. Even our posture, gait and joints are affected! Our muscles provide the force and strength to move our bodies, which is affected by the changes in our muscles and joints. This can result in weakness and a slowing down in our movement, especially as the vertebrae in our spines lose fluid and become thinner.

    Because our bones in our arms and legs can become more brittle, due to mineral loss and can break more easily, Joints become stiffer and less flexible as the fluid in the joints decreases. Hip and knee joints may begin to lose cartilage (degenerative changes). Finger joints lose cartilage and the bones thicken slightly, which is common in women. Our lean body mass decreases with age and inactivity too. This decrease is partly caused by a loss of muscle tissue known as atrophy. Muscle changes can begin in the 20s in men, and in the 40s in women. Muscles are less toned and less able to contract because of changes in the muscle tissue and normal change in the nervous system. Muscles may become rigid with age and may lose tone, even with regular exercise.

    EFFECTS OF CHANGES
    Breakdown of the joints may lead to inflammation, pain, stiffness, and deformity. Joint changes can affect almost all older people. These changes range from minor stiffness to severe arthritis or debilitating osteoporosis. The posture may become more stooped (bent). Movement slows down and may become limited. Walking may become unsteady, and there is less arm swinging. Older people get tired more easily and have less energy.
    COMMON PROBLEMS
    The risk of injury increases because of unsteady gait changes, instability, and of course, loss of balance, which leads to falls. People who are unable to move on their own, or who do not stretch their muscles with exercise, may get muscle contractures. I cannot imagine how this could make one feel!

    PREVENTION
    I know that exercise and even just daily walking are the best ways to slow down or even prevent problems with the muscles, joints, and bones. Doing this can help us maintain strength, balance, and flexibility. Regular exercise will help our bones stay strong! I just need to kick my New Year’s resolution into gear so that I can follow through with getting out there and doing this at the gym - tomorrow!!
    I also know, as most of us do, that eating a well-balanced diet with plenty of calcium is especially important for women! We need to be particularly careful to get enough calcium and vitamin D as we age. It is recommended that postmenopausal women, and men over age 70, should get at least 1,200 mg of calcium per day and should have 800 international units (IU) of vitamin D daily. I am trying to do this for myself this year too. I am making a concerted effort towards eating more healthily. After learning about how being sedentary can completely adversely affect everything about our lives as we get older, I am now determined not to allow these things to happen to me! Because I work in healthcare, and because I know that getting involved in medical research such as KGK offers, this can lead to the opportunity to make a difference in people’s lives! I completely believe in this study, and would recommend anyone moving toward their senior years to consider participating in this very worthwhile and exciting study!

    Eileen Harrison