Transcript Aging of Cardiac Muscle and Cardiac Failure

Aging of Skeletal Muscle
Dr. Franco Navazio
Muscles
There are 660 skeletal muscles in adult humans
These constitute 45% to 50% of the normal body weight
Their primary purpose is to provide “MOTILITY”
In addition, they represent the major site for:
- energy transduction
- energy storage
- primary support system
Anatomy
Skeletal muscle is composed of
Muscle fascicles are composed of
Muscle fibers
(multinucleated cells, the longest in the body)
Each fiber is composed of MYOFIBRILS and, within the
myofibril structure, the contracting machinery is the
SARCOMERE
Sarcomeres are composed of digital thin filaments, the
“ACTINS,” and interdigitated thick filaments: the
MYOSINS
Anatomy
• 2 membranes surround the muscles:
– outer membrane: the basement membrane (very permeable to
solutes and proteins or to other metabolites)
– inner membrane: SARCOLEMMA is located just beneath the
plasma membrane (a true cell boundary)
• An intact sarcolemma is critically important:
– it maintains a proper acid-base balance of the fibers
– propagates the action potential (starting at the neuromuscular
plaque leading to the muscle contraction)
Contraction
The actors:
• Ca++ passes through the sarcolemma; in its presence there is
hydrolysis of ATP (ADP+P) which releases energy
• ADP binds to ACTIN: meanwhile, a regulatory protein (enzyme)
TROPONIN (activated by this energy) binds to MYOSIN
forming TROPOMYOSIN--shifting the ACTIN helix and
leading to CONTRACTION
End result: the ACTOMYOSIN complex
• Contraction could involve lengthening or shortening
mechanisms, depending on the movement pattern
• MEMO the TETANIC contraction
GENDER EFFECT
In both sexes, strength & power can only be obtained after
myelination of the afferent nerves, reached at maturity.
Maximum gain in muscle strength is reached in boys by
testosterone & in girls by estrogens, all of these stimulated
by gonadotropins.
Low levels of testosterone and other androgens (e.g.
androstenedione) are also present in girls. The higher fat
percentage induced in girls by estrogens should be
considered. Female swimmers with higher body fat
percentage have a significant advantage.
Growth hormone has lesser effect in both sexes (a
regulator of protein synthesis).
Satellite Cells
Peripheral location
and activated by traumatic stress.
They may provide
compensatory growth of existing fibers
or growth of regenerating fibers
SARCOPENIA:
Loss of muscle tissue
Most significant physiological change in muscle is with AGE
Looking at muscles, fat and bones, we see that:
At age 20, muscles are 45%, fat 20% and bones 12% of
the total weight
At age 75, muscles are 15%, fat 40% and bones 8%
After age 49, there is a loss of 1.2 kg (3lbs) of muscle per
decade
DURING SARCOPENIA:
The loss appears to be more significant for the FAST
FIBERS type 1 and 2 (or FO and FOG) while the SLOW
FIBERS (or SO) are more stable.
This fact clarifies at least in part why a 9-year-old
grandson can beat grandpa easily in a 100m run but
will tire much sooner in a 10km hike.
Reminder: The fast fibers (normally more pale) fatigue
more easily while the slow (more red) are more resistant
to FATIGUE.
THE ETIOLOGY of SARCOPENIA due to
a) inactivity
b) decreased protein synthesis
c) plus neural, hormonal and nutritional factors
SARCOPENIA is aggravated:
by the relative deficiency of the anabolic hormones (GH, Insulin-like
GH, DHEA)
BUT and AGAIN
of greater importance is the DECREASE of VIGOROUS MUSCULAR
WORK
Any acute illness forcing elderly persons to bed rest is provoking a
loss of muscle mass of about 1.5% per day
Hence for 1 day of bed rest, up to 2 weeks of intense reconditioning
is necessary.
Sarcopenia harder for the FAST PALE FIBERS,
but why?
WE DO NOT KNOW
but…
fiber characteristics can be modified by different
modalities like hormonal administration and/or by specific
exercises or activities
The change in the fiber characteristic is defined as
MYOPLASTICITY
MYOPLASTICITY
May occur with different clinical effects,
namely:
-muscles enlarge with resistance type of exercise
-increase their contractility (and the number of
mitochondria) with endurance type of exercises
-all these changes are due to stimulations and variations in
the characteristics of the MYOSINS (protein isoforms)
CLINICAL significance of Myoplasticity:
RESISTANCE training: increases amount of contractile
proteins permitting increasing efforts.
As a consequence, muscles do ENLARGE (a decrease in Ca++
concentration is needed to elicit 50% of maximal tension).
ENDURANCE training: increases the velocity of contraction,
increases the number of mitochondria, and increases the capacity to
oxidize substrate
•Increase the Vmax (velocity of contraction) of the SO (slow) fibers
•Decreases the Vmax of the FO (fast) fibers
•Vmax = velocity of shortening of a fiber
BENEFITS OF EXERCISE TRAINING
(see lecture by Prof. Brooks)
• Prevention of bone loss
• Improvement of postural stability
• Psychological benefits are to be added like preservation of
cognitive functions, reduced incidence of depression and enhanced
self-efficacy.
• Prevention of colonic cancer possibly due to increased GI transit time
and stimulation by GH and IGF-1.
CLEAR BENEFITS OBTAINED WITH EXERCISE:
• Metabolic: increased insulin sensitivity and glucose tolerance.
• Cardiovascular: reduces blood pressure, helps vasodilation,
reduces incidence of arrythmias
•Cerebral: enhanced brain blood supply and reduced episodes of
thrombosis
• Improved equilibrium hence fewer falls
• Lower mortality rate
• Higher HDL/LDL ratio
HOWEVER
PROLONGED AND SEVERE EXERCISE MAY
HAVE DELETERIOUS EFFECTS
NOTES OF ALERT
The Menstrual Cycle
• Should not be disrupted
• Excessive training stress and poor diet, all increase the
incidence of amenorrhea.
• The consequences are: infertility, premature bone loss,
muscolo-skeletal injuries and scoliosis
• ALL OF THESE PROBLEMS are totally preventable
with planned and supervised type of exercise
TO BE AVOIDED: THE ERGOGENIC AIDS
or the dreams, the failures, the tragedies
THE BANNED SUBSTANCES: the DOPING CLASS
1) Stimulants like amphetamines, efedrine and even caffeine if
reaching a high blood concentration
2) Beta-2-agonists like the inhalers (ventolin, albuterol and
terbutaline)
3) Narcotic analgesics (or pain killers) like derivatives of
morphine or codeine
4) Diuretics
5) Hormones like gonadotropin, corticotropin and
erythropoietin (EPO)
6) And certain restrictions for alcohol, marijuana and
corticosteroids
ALSO TO BE AVOIDED:
THE ANABOLIC STEROIDS: namely testosterone but especially
its derivatives manufactured to:
a) minimize the sexual properties
b) maximize the anabolic properties
POSITIVE EFFECTS:
a) increase the rate of protein synthesis
b) increase strength, power and muscle size
c) improve endurance capacity
MAJOR SIDE EFFECTS:
a) serious liver toxicity
b) elevation of blood pressure
c) increase levels of LDL decrease levels of HDL
d) increase of the blood sugar level and in addition masculinization,
increased or decreased libido, acne, depressed immune function and
even psychosis