Sarcopenia LU

Sarcopenia is considered to be

the "age-related" loss of muscle mass

In Sarcopenia you need to realize that it is

much more complicated than "age-related loss" and there are factors other than age

Sarcopenia Age Factors

- can begin as early as the 30's - a result of 50% or more loss in muscle mass by the time one reaches their 70

There is certainly a "normal" decline in muscle mass as we age, that is not

sarcopenia

The critical distinction is that sarcopenia is an

accelerated decline in muscle mass caused by intrinsic and extrinsic factors

sarcopenia directly impacts

a person's function

Sarcopenia secondarly effects

a decrease in strength, endurance, and exercise capacity

Sarcopenia is also associated with

- increased insulin resistance

- higher fall rates

- obesity

- greater mortality risk.

as the understanding of sarcopenia improves, it is highly likely that a

large genetic predisposition or epigenetic triggers will be identified

Intrinsic causes of sarcopenia

- age-related muscular changes

- mitochondrial dysfunction

- motor axon declines

- inflammatory pathway activation

- comorbid disease triggers

- hormonal changes

- reduction in satellite cells

Extrinsic causes of Sarcopenia: Decline in physical activity

- forced secondary to disease

- change in life style

Extrinsic causes of Sarcopenia: Altered Nutrition

- decreased intake

- excessive intake

- poor food choices

- medication influences

- disease influences

The underlying causes for the lifestyle change are multifactorial and include things such as: (reduced level of PA, "use it or lose it")

- Physical limitations imposed by chronic illness

- Changes in social interests

- Changes in family responsibilities

- Physical inability to continue preferred activities

- Environmental changes that limit the availability of activities

Intrinsic Causes of Sarcopenia: Age-related molecular changes include

- changes in tissue growth factor-Beta signaling

- the up-regulation of proteins associated with apoptosis

- changes in the angiotensin system

- all leads to a reduction in muscle fibers.

Intrinsic Causes of Sarcopenia: Mitochondrial dysfunction

maintenance of muscle fibers requires normal mitochondrial function

Intrinsic Causes of Sarcopenia: Motor axon loss

aging can result in a reduction of motor axons. It appears that in sarcopenia there is a greater loss of axons innervating fast-twitch muscle fibers (Type II)

Intrinsic Causes of Sarcopenia: Inflammatory pathway activation

occurs as part of chronic diseases and is also thought to be a normal component of aging

Intrinsic Causes of Sarcopenia: Co-morbid disease triggers

- many chronic diseases (diabetes, hypertension, renal disease, CHF, COPD, etc.) are associated with increased markers of inflammation

- Obesity is also thought to be a trigger for sarcopenia and in fact, there is a form of sarcopenia is called sarcopenic obesity

Intrinsic Causes of Sarcopenia: Hormonal changes include

- inhibition of growth hormone

- a decrease in plasma insulin-like growth hormone

- insulin resistance

- a reduction in testosterone or a decrease in estrogen

- all can lead to a loss of muscle mass.

Intrinsic Causes of Sarcopenia: Reduction in satellite cells

satellite cells repair and replace damaged muscle cells. A reduction in satellite cells means a decreased capacity for repair and regeneration

sarcopenia causes a loss in muscle mass but of particular interest is

muscle power (power = force generated per unit time) seems to be more influenced by the mass reduction than muscle strength alone

So in Sarcopenia not only is the person weaker,

they are less able to rapidly generate force

the loss of muscle power is a more important predictor of

functional losses than the loss of muscle strength

Specific changes in muscle fibers include:

- A decrease in muscle fiber numbers with a greater loss of fast-twitch fibers

- A decrease in the size of the remaining muscle fibers

- there is an impairment in the excitation-coupling mechanism of many of the remaining muscle fibers

If in Sarcopenia You Add the neurologic based changes that impact muscle, motor axon loss and changes in neuromuscular junction dysfunction,

it becomes very clear why the patient experiences such a functional decline

With the reduction in muscle mass,

there is a concomitant reduction in basal metabolic rate

As a result of reduced basal metabolic demands,

- the body requires fewer baseline calories to maintain itself

- the person will gain weight.

- The primary tissue added in the associated weight gain is fat, which further perpetuates sarcopenia.

A reduction in muscle mass also can lead to

a decrease in bone density and thus a decrease in bone strength

Muscle forces applied to the bone, assist in

the maintenance of bone mass as does weight-bearing physical activity

the loss of muscle mass also can lead to

impaired reflexes and coordination

Beyond reduced strength and mobility, sarcopenia leads to:

- Decreased metabolic rate- contributes to weight gain

- Impaired reflexes and coordination - affects overall function and fall risk

- Increased insulin resistance - contributes to the development of metabolic disorders

- Higher mortality risk - makes sarcopenia a significant health concern

Sarcopenia typically presents as

a greater than expected decrease in muscle strength, muscle mass, and physical function/performance

Sarcopenia Clinical Presentation features

- The loss of strength is enough to negatively impact normal ADLs

- People with sarcopenia are often sedentary and most are over 60 years old

- Many will have comorbid disorders

The medical diagnosis of sarcopenia relies on

a number of functional performance measures as well as measures to quantify muscle mass

Sarcopenia, patient self-report scale

- SARC-F

- Scores greater than or equal to 4 suggest need of other tests

Techniques for measuring a patients muscle mass in sarcopenia

- CT

- MRI

- DEXA

- bioimpedance

- diagnostic ultrasound

Generally speaking the goal of body composition measurement is to

identify fat-free mass vs body fat

Skeletal muscle is a component of the fat-free mass so by changing the algorithms,

an estimate of muscle mass can be separated out

The results of these tests (physical performance and muscle mass) are used to

classify patients as not sarcopenic, probable sarcopenia, sarcopenia, and severe sarcopenia

Biomarkers in Sarcopenia: Myokines

Proteins like myostatin (promoting muscle breakdown) and follistatin (inhibiting myostatin) are being studied for diagnostic and therapeutic potential

Biomarkers in Sarcopenia: Growth Differentiation Factor-15 (GDF-15)

Elevated levels correlate with lower muscle mass and strength, as well as age-related anorexia

Biomarkers in Sarcopenia: Inflammatory biomarkers

IL-6, TNF-α, and CRP reflect the "inflammation" process contributing to sarcopenia

Biomarkers in Sarcopenia: MicroRNAs

Particularly miR-133a, miR-206, and miR-499, which reflect muscle tissue damage and regenerative capacity

Biomarkers in Sarcopenia: Metabolomic profiles

These comprehensive signatures may better capture the multifactorial nature of sarcopenia

Medication treatment for sarcopenia,

There are currently no medications approved for the treatment of sarcopenia so medical intervention focuses on treating the comorbid diseases that are associated with sarcopenia

There is evidence that substantially increasing dietary protein intake coupled with an appropriately prescribed resistance exercise training program can

reverse at least some of the muscle loss and related functional declines

in addition to dietary protein intake other nutritional factors under investigation in the treatment of sarcopenia: Vitamin D supplementation

thought to be necessary for optimal muscle function

in addition to dietary protein intake other nutritional factors under investigation in the treatment of sarcopenia: Omega-3 fatty acids

might enhance anabolic response to training and reduce inflammation

in addition to dietary protein intake other nutritional factors under investigation in the treatment of sarcopenia: Creatine

there is a need to study this form of supplementation for safety and effectiveness in the sarcopenic population

Appropriately prescribed exercise training programs can

reduce, slow, and reverse sarcopenia at least to a limited extent

To address sarcopenia, the exercise program must include

resistance exercise

Sarcopenia: Aerobic exercise

- dont ignore it

- not enough to address loss in muscle mass