Physiologic Changes of the

Musculoskeletal System
w i t h A g i n g : A Brief Review
a,b,
Walter R. Frontera, MD, PhD *

KEYWORDS
 Older adults  Skeletal muscle  Weakness  Sarcopenia

KEY POINTS
 The number and percentage of people in older age groups is increasing significantly in
most countries of the world resulting in important socioeconomic and health challenges.
 Many components of the musculoskeletal system, including skeletal muscle, tendons, lig-
aments, bone, and articular cartilage, show significant losses of structural and functional
properties.
 Age-associated changes in musculoskeletal tissues compromised an individuals capac-
ity to perform many activities of daily living as well as more demanding tasks.
 Many of the age-associated changes seen in the musculoskeletal system can be partially
modified with an active lifestyle and appropriate exercise training.

INTRODUCTION

The World Health Organization has recognized the aging of the population in many
countries around the world as one of the most significant challenges of the twenty-
first century.1 In several countries in Asia and Europe, the average life expectancy
has already exceeded 80 years, particularly among women. In fact, the fastest
growing age group in the United States is the oldest-old (>85 years) group. It has
been estimated that by the year 2025, the number of people older than 60 years in
the planet will exceed 1 billion and 2 billion by the year 2050.1,2 Although there are sig-
nificant differences between countries associated with sociopolitical conditions and
the level of income, the increase in life expectancy and in the number of people in
this age group has been documented in low-, middle-, and high-income countries.3

Disclosure: The author has nothing to disclose.

a
Departments of Physical Medicine, Rehabilitation, and Sports Medicine, School of Medicine,
University of Puerto Rico, PO Box 365067, San Juan, PR 00936-5067, USA; b Department of Phys-
iology, School of Medicine, University of Puerto Rico, PO Box 365067, San Juan, PR 00936-
5067, USA
* Departments of Physical Medicine, Rehabilitation, and Sports Medicine, School of Medicine,
University of Puerto Rico, PO Box 365067, San Juan, PR 00936-5067.
E-mail address: walter.frontera@upr.edu

Phys Med Rehabil Clin N Am 28 (2017) 705711

http://dx.doi.org/10.1016/j.pmr.2017.06.004 pmr.theclinics.com
1047-9651/17/ 2017 Elsevier Inc. All rights reserved.
706 Frontera

It should not come as a surprise that these changes in the age-group composition of
the population have significant social, economic, political, and health implications.4
Thus, understanding age-related changes in human physiology and their conse-
quences is of significant interest and relevance and has been identified as a research
priority by the US National Institutes of Health.5
The main challenge associated with advanced adult age is the relationship between
significant alterations in many physiologic functions, the development of multiple im-
pairments, the decline in overall functional capacity, the associated morbidity and
mortality, and the resulting loss of independence that most older adults fear more
than death. For example, because maximal physiologic capacities are greatly dimin-
ished with age, the ability to perform physical tasks at the same absolute level of en-
ergy expenditure or muscular force becomes limited. In other words, activities such as
rising from a chair or crossing a city street intersection that usually represent submax-
imal demands can become, in old age, maximal or impossible efforts (Fig. 1). It should
also be noted that physical or architectural obstacles may contribute to this problem
by making the environment less friendly.
Some of the most important contributors to the functional loss leading to impair-
ment and disability are the multiple changes in structure and function of the musculo-
skeletal system. Left unchecked, life-threatening complications, such as falls and
bone fractures associated with muscle weakness, can occur. In fact, mortality after
a fall resulting in a fracture is higher in those with a lower level of muscle strength
before the fall. The biological changes resulting from aging contribute to a decline in
skeletal muscle strength and mass, alterations in muscle contractile properties,
impaired motor performance, a reduction in bone mass and strength, a decrease in
flexibility and joint range of motion, and the loss of the capacity of soft tissues to sus-
tain and recover from injury. It is interesting that the qualitative nature of these changes
is very similar to those experienced during the inactivity that follows injury or hospital-
ization underlining the contribution of a sedentary life, inactivity, and immobilization to
the age-associated loss of function and independence.

MUSCLE STRENGTH

Skeletal muscle strength is one of the fundamental physiologic capacities that

contribute to functional capacity. Muscle strength alone is a strong predictor of severe
mobility limitation, slow gait speed, increased fall risk, risk of hospitalization, and high
mortality rate. For example, older adults with poor muscle strength have a 2.6-fold

Fig. 1. Force required to rise from a chair relative to the strength of a person. At 20 years of
age, the maximal voluntary contraction (MVC) is much higher than the force required to
perform a simple task, such as rising from a chair. Because of the reduction in muscle strength
with aging, the same task may represent a maximal effort in an 80-year-old person.
 Aging of the Musculoskeletal System 707

greater risk of severe mobility limitation, a 4.3-fold greater risk for slow gait speed, and a
2.1-fold greater risk of mortality compared with older adults with high muscle strength.6
Aging is associated with a significant reduction in muscle strength, defined as the
capacity to generate maximal force at a specified velocity (zero in the case of isomet-
ric/static muscle actions). Cross-sectional studies have shown that both older men
and women have lower strength in multiple upper and lower limb muscle groups
when compared with their younger counterparts. Furthermore, longitudinal studies
have shown that this reduction in muscle strength is approximately 1.0% to 1.5%
per year7 and it is more noticeable in the lower limbs (knee extensors and flexors) of
men and women and almost nonexistent in the upper limbs in women. Equally rele-
vant, and perhaps more significant from a functional point of view, is the reduction
in muscle power or the product of force times velocity.8 This reduction has been esti-
mated to be approximately 2.9% per year and is very important because the success-
ful performance of many activities of daily living depends more on the generation of a
certain level of force quickly than in maximal levels of force that are almost never
required during daily life.
One factor that may contribute to a decline in muscle strength and power is the
reduction in the ability to activate motor units. This point is particularly true in healthy
older humans who are not mobility impaired.8 Both central and peripheral factors may
contribute to this reduction in neuromuscular activation, including a decline in central
nervous system drive, changes at the level of the spinal cord, and alterations of the
peripheral nerve and neuromuscular junction. On the other hand, in the case of
mobility-impaired patients, the loss of muscle power is due to a combination of deficits
in muscle strength and contraction velocity.

MUSCLE SIZE

Skeletal muscle comprises approximately 40% of the human body weight and con-
tains between 50% and 70% of all proteins in the human body. Therefore, muscle at-
rophy is an important determinant of muscle dysfunction in elderly. The correlation
between muscle strength and muscle size is positive but not perfect, and the age-
associated reduction in strength is only partially due to the loss of muscle mass.
This loss of muscle mass together with changes in function (walking speed) and
strength is known as sarcopenia.9 It has been known for several years that both a
decline in the number of muscle fibers (mainly those expressing type II myosin heavy
chain isoform) and a reduction in muscle fiber size contribute to muscle atrophy in
older men and women.10 Sarcopenia affects muscles of both upper and lower limbs
as well as the paraspinal muscle group.11 It must be noted that these changes in mus-
cle mass seen on imaging studies are accompanied by increases in fat and changes in
muscle density that correlate well with changes in muscle function.

MUSCLE QUALITY AND ALTERATIONS IN SINGLE MUSCLE FIBERS

The concept of muscle quality has been developed to indicate alterations in muscle
function that are independent of changes in muscle mass or size (cross-sectional
area). At the macroscopic level, these changes are reflected in reductions in muscle
density as measured with MRI studies and increases in intermuscular fat.11 At the sin-
gle fiber level, older people have lower specific force or force adjusted for differences
in muscle fiber size (a physiologic index of muscle quality).12 It is interesting that lon-
gitudinal studies show that surviving fibers may maintain normal strength and short-
ening velocity in an attempt to compensate for the fibers that have been lost as a
result of the aging process.13
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DETERMINANTS OF FORCE, POWER, MOVEMENT, AND FUNCTION

There are 4 general domains that contribute to the capacity of skeletal muscle to
generate force, power, and movement.14 These 4 domains are structure and
architecture, fiber type distribution, excitation-contraction coupling, and energy
release. There is very good scientific evidence in support of age-related alterations
in all 4 domains. (Table 1) For example, as mentioned earlier, the number of
muscle fibers is reduced with age, particularly fibers expressing type II myosin
heavy chain isoform. This loss of muscle fibers is accompanied by a reduction in
average muscle fiber cross-sectional area of both type I and II fibers. Skeletal mus-
cle may not be able to compensate for this loss because regeneration of muscle
fibers is limited because of a reduction in the number of satellite cells, particularly
those associated with type II fibers. Furthermore, activation of existing satellite cells
is also impaired. As a consequence of this, fiber type distribution is altered with a
small increase in the percent of type I fibers, a significant reduction in type II fibers,
and an increase in the number of hybrid fibers expressing more than one myosin
heavy chain at the same time. The functional significance of these hybrid fibers is
unknown, but some investigators considered them to be immature fibers or
fibers in transition. Further, significant alterations and fragmentation in the triad,
including the t-tubule and sarcoplasmic reticulum system, result in impaired cal-
cium release and uncoupling of the excitation-contraction processes. Finally,
some studies, but not all, demonstrate significant impairment of oxidative
pathways, including a reduction in mitochondrial volume and capacity. Various
combinations of the changes described earlier result in an impaired capacity to
perform a spectrum of activities typical of daily life that have different power
demands.
The mechanical process at the molecular level that underlies muscle weakness is a
dysfunctional formation and interaction of actin-myosin cross-bridges. The number of
cross-bridges in the strong-binding state is lower in aged muscle resulting in muscle
weakness. Similarly, the dissociation of actin and myosin that determines the short-
ening velocity of the muscle fiber is impaired. One of the explanations for these
changes is the presence of posttranslational chemical alterations of motor proteins,
such as myosin including glycation and oxidation. In other words, biochemical alter-
ations known to occur with aging can explain some of the functional alterations in
muscle force and power production.15

Table 1
Summary of age-related changes in skeletal muscle

Muscle strength Lower

Muscle mass Lower
Muscle quality Increase in fat and connective tissue
Fiber number Lower (particularly type II)
Fiber type distribution Increase type I and reduced type II
Fiber specific force Lower
Excitation-contraction coupling Impaired (uncoupling and fragmentation of
cellular elements)
Energy release Reduced oxidative capacity
Muscle proteins (myosin) Altered because of biochemical changes
Satellite cells Decline in those associated with type II fibers
 Aging of the Musculoskeletal System 709

TENDONS

Tendons are important anatomic structures because they transmit the force devel-
oped by muscle cells to bones, making movement possible. The fundamental
biochemical component of tendon is type I collagen organized in fibrils that represent
the force-transmitting unit of the tendon. These fibrils are stabilized and strengthened
by cross-links between collagen molecules and embedded in extracellular matrix
composed of cells (fibroblasts) and proteoglycans. Tendons respond to mechanical
loading and unloading and are at risk of injury during activities, such as daily house-
hold activities, work-related activities, exercise training, and sports participation.
The effect of aging on tendon structure and function has been recently
reviewed.16,17 Tendon tissue injuries seem to be more frequent with aging, including
the tendons of the rotator cuff, the patellar tendon, and the Achilles tendon. It has
been suggested that genetic factors may contribute to tendinopathy in older patients
with rotator cuff disease.18 When compared with immature tissue, the most important
effects of aging on tendons include a reduction in cell density, a decline in matrix turn-
over, an increase in cross-links particularly in nonenzymatic cross-links called
advanced glycation end products, a mild reduction in fibril diameter, and a reduction
in the elastic modulus. The importance of glycation is that it increases the distance be-
tween collagen molecules and reduces water content. These alterations change the
mechanical properties of the tissue resulting in an increased susceptibility to injury.
Finally, short-term immobilization (2 weeks) of human elderly tendon reduces collagen
protein synthesis, although no significant change in mechanical properties was
noted.19 It has been suggested that the effects of aging and exercise on tendons
are mediated via changes on tendon stem/progenitor cells. In other words, aging im-
pairs proliferation of stem cells and reduces its ability to regenerate, whereas exercise
increases proliferation of stem cells.20

LIGAMENTS

Ligaments provide important joint support and stability. From biochemical and biome-
chanical points of view, the changes in ligaments seen with aging are similar to those
described earlier for tendons.16,21 These changes include decreases in collagen syn-
thesis and concentration, elastic modulus (an indication of accumulated damage and
risk for further damage), and ultimate force. Similarly, there is an increase in failure
strain. Further, the expression of some proteoglycans that serve as lubricants on
the surface of the ligament and between collagen fiber bundles is increased. It has
been suggested that these changes taken together explain the higher incidence of
ligamentous injuries in older people.22

BONE

A well-known change in bone health with advanced adult age is a reduction in bone
mineral content and density. In the United States, recent data from the National Health
and Nutrition Examination Survey show that the prevalence of osteoporosis in adult
(aged 501 years) women was 9.8% (femur), 11.6% (lumbar spine), and 16.5% (either
femur neck or lumbar spine) depending on the anatomic area studied.23 In general, this
study suggests a higher prevalence in osteoporosis compared with 2007 to 2008.
Further, the prevalence of low bone mass ranged from 36% to 53%, also in women.
Both conditions were found in men, but the prevalence was significantly higher in
women. In addition, non-Hispanic blacks showed a lower prevalence of osteoporosis
and low bone mass.
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The presence of osteoporosis and/or low bone mass contributes to the high risk for
fractures in the elderly because it increases bone fragility. This risk is complicated by
the fact that mechanical loading in the form of physical activity is reduced in older peo-
ple.24 It has been proposed that dynamic mechanical loading, and not only weight-
bearing activities, is required to strengthen bone architecture. There is good scientific
evidence from clinical trials of the benefits of exercise training on bone mineral density
in older adults.25
The various components of the musculoskeletal system interact with each other and
influence their individual response to the aging process. Changes in both muscle and
bone tissues can result in significant impairment and disability. Thus, it is important to
note that components of sarcopenia (reduced muscle strength, mass, and perfor-
mance) are significantly associated with osteoporosis.26

ARTICULAR CARTILAGE

The effects of aging on articular cartilage and related tissues has been recently
reviewed.27 Aging is associated with a higher prevalence of chondrocytes that have
lost their ability to divide (diminished mitotic activity). The loss of chondrocytes is facil-
itated by trauma and excessive mechanical loading and may be mediated by
increased oxidative stress associated with loading. In addition, older chondrocytes
have reduced ability to synthesize components of the extracellular matrix, such as
collagen and ground substance.
Stiffness of the collagen network in many tissues, including articular cartilage, in-
creases with age because of an increase in cross-links by advanced glycation end
products. The functional consequence of these changes is a reduction in the capacity
for deformation that may lead to injury. Finally, the synthesis of proteoglycans, an
important component of the ground substance, is decreased with advanced adult age.
It is interesting to note that lack of mechanical stimulation, typical of bed rest and
immobilization prevalent in old age, results in thinner and softer articular cartilage.
Some studies have suggested that exercise training has the opposite effect.

SUMMARY

The musculoskeletal system undergoes significant changes with advanced adult age.
The structural and functional properties of all the tissue elements of the system change
reducing their capacity to enhance mobility and withstand injury. More research is
needed to understand the mechanisms underlying these losses and the potential of
physical activity and exercise to preserve more normal tissue characteristics.

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