Transcript Biological Theories of Aging

Physiology of Aging
Min H. Huang, PT, PhD, NCS
Reading assignments
• Guccione: Ch 3, Ch 7 (pp. 104-113 only),
(Ch 15, pp. 272-278 prn)
Learning objectives
• Identify and interpret physiologic changes
that occur with aging.
• Adapt physical therapy management to
address age-related and life-style related
declines in physiological systems.
A geriatric client at ICU
73-year-old, active woman with a past
history of hypertension and atrial fibrillation.
She underwent a routine cardioversion for
atrial fibrillation but developed multiple
complications, including sepsis and
respiratory failure.
The patient spent 3 weeks of limited
activity in the ICU and was transferred to
long-term acute care hospital.
4
Questions to consider
• What is your assumption about this patient’s
expected outcomes?
• How might your personal biases/assumptions
affect your interview with this patient?
• How might your knowledge of age-related
declines in physiological systems affect your
clinical decision making?
OVERVIEW OF AGEDRELATED PHYSIOLOGICAL
CHANGES
Ropper 2009 (in Adams and Victor’s)
Age-Related Changes in Body
Composition/Metabolism
Age-Related Changes in Body
Composition/Metabolism
• Most of the fat increase occurs inside the
peritoneum
• Fat significantly contribute to increased
whole body inflammation, age-related
declines, and diseases
• Exercise increases metabolic rate and can
burn fat as energy sources
Age-Related Changes in Body
composition/Metabolism
• Decreases
―Lean body mass
―Strength ↓ about 8% per decade after 30 y.o, not
linear but slow in the beginning and accelerates as
age
―Healthy 80-90 y.o. have shown 20-40% ↓ n in max
isometric force
• Increases
―Fat Mass (contributes to strength and mobility
limitations)
―LDL cholesterol
Sarcopenia vs. Cachexia
Sarcopenia
Cachexia
• Age-related loss of
muscle mass; decreased
muscle strength and rate
of force production
• Amenable to change
• Strengthening exercise
can significantly ↑ muscle
mass and strength
• Contribute to the decline
in functional ability and
frailty
• Muscles will NOT
respond to exercises
• Complex pathophysiology
including changes in body
metabolism
• Ongoing loss of muscle
loss, loss of nutrition,
caused by negative
balance between protein
and energy.
Cachexia
“… a multifactorial syndrome defined by an
ongoing loss of skeletal muscle mass (with or
without loss of fat mass) that cannot be fully
reversed by conventional nutritional support
and lead to progressive functional
impairment..………. pathophysiology is
characterized by a negative protein and energy
balance driven by ↓food intake and abnormal
metabolism.”
Fearon, 2011
Stage of Cachexia
Fearon, 2011
Age-Related Changes in Skeletal
Tissue
• Basic metabolic unit (BMU)
―Osteoclast, osteoblast, osteocyte
• Aging
―↑ bone breakdown rate (osteoclast activity)
―↓ bone accretion rate (osteoblast activity)
• Decline in bone mineral with age
―Begins in the 3rd decade at a rate 0.5% to 1%
yearly
―~ 2% yearly for the 5-year peri- and
menopausal era
• Non-modifiable risk factors for bone loss
• Modifiable risk factors for bone loss
Hip Fracture: How big is the problem
in people age 65+ years?
• In 2007, 281,000 hospital admissions for hip
fractures
• Over 90% of hip fractures are caused by
falling, most often by falling sideways
• In 1990, it was estimated that by 2040, the
number of hip fractures would exceed
500,000, although the rate of hip fracture has
in fact, declined in recent years.
• In 1991, Medicare costs for hip fractures
were estimated to be $2.9 billion.
Age-Related Changes in Collagenous
Tissues and Clinical Consequences
Age-Related Changes in Cardiovascular
Tissues and Clinical Consequences
Age-Related Changes in Nervous
System and Clinical Consequences
Age-Related Changes in Immune
System and Clinical Consequences
Age-related changes
Clinical Consequence
Increase in proinflammatory
cytokines (e.g. interleukin 1 and
10, tumor necrosis factor-α)
Increase in systemic inflammation,
leading to Alzheimer’s disease,
atherosclerosis, cancer, diabetes
Metabolic syndrome
Fat mass, an inflammatory organ,
shift from the periphery to the
abdomen; an increase in intraabdominal fat
Muscle wasting
Affect function of body systems
(reducing the window of
homeostasis)
Age-Related Changes in Hormonal
Axis
• Loss of sex hormones with age ↓ muscle
mass and muscle strength
• Testosterone levels gradually decline at ~ 1%
a year after age 30. By about age 70, the
decrease can be as much as 50%.
• Testosterone replacement in men ↑ lean
muscle mass, but resistance exercise +
testosterone replacement is required to ↑
muscle strength
Age-Related Changes in Hormonal
Axis
• Estrogen replacement in women ↑ in strength
and lean mass in postmenopausal women
• Findings from the Women’s Health Initiative
(WHI), a 15-year study launched in 1991
―Hormone medication (whether estrogen + progestin
or estrogen only) resulted in an increased risk of
stroke and blood clots
―Estrogen + progestin resulted in an increased risk of
heart attack and breast cancer
http://nccam.nih.gov/health/menopause/menopausesymptoms#hed1
Estrogen Loss and Manifestations
of Health Risks Over Time
Menopause Is Associated With an
Accelerated Loss of Bone Mass
• Decreased cortical thickness is associated
with hip fracture
After adjustment for age and race, the women not
using Hormone Therapy in the previous year had a
55% increased risk of hip fracture
http://www.medscape.com/viewarticle/752892_3
AGE-RELATED CHANGES IN
SENSORIMOTOR AND
NERVOUS SYSTEM
http://www.youtube.com/watch?v=HmuBnYVh6xE
Neuro-ophthalmologic Signs
• Progressive smallness of pupils
• Decreased reactions to light and
accommodation
• Far-sightedness (hyperopia or presbyopia)
• Insufficiency of convergence (problem with
focus and depth perception)
• Restricted range of upward conjugate gaze
• Diminished dark adaptation
• Increased sensitivity to glare
Age-Related Visual Changes
• Visual acuity & field decrease with aging
• Increased difficulty seeing blues & greens
• Spatial visual changes occur making it
difficulty to see slow moving objects
• Changes with accommodation, contrast, &
depth perception
• Control of smooth pursuits and saccade is
decreased
Problems in Vision
• Glaucoma (98% blindness preventable)
―Peripheral vision lost 1st then central
• Cataracts: opacity of the lens
―Medicare: #1 surgery
―Central vision lost 1st
―Sunglasses for prevention
• Macular Degeneration
―Risk increases with age 28% those older than 75
―Central vision primarily affected
―Quality of life with reading, tv, sewing
J. Blackwood
What is this
an example
of?
J. Blackwood
J. Blackwood
What is this?
J. Blackwood
Other areas of visual loss
• Diabetic retinopathy
• Retinal detachment
• Legal blindness
J. Blackwood
PT Considerations in Visual Deficits
Associated with Aging
•
•
•
•
•
•
•
Adaptation of HEP instructions
PT gym/room, hallways with deco
Patterns of flooring
Safety in environment, provide adequate light
Use of contrasting colors for safety
Avoid abrupt changes in light, nightlights
Large print, low vision aids, assistance both
verbal and tactile
J. Blackwood
Hearing Loss with Aging
• May be masked as dementia
• More loss with high tones
• Peripheral hearing loss (conduction hearing
loss)
• Sensorineural loss
• Presbycusis
―decrease in auditory acuity resulting from
degenerative changes in the inner ear with age (a
reduction of the number of hair cells)
• Tinnitus
J. Blackwood
Communication Aids
• Hearing aids, amplification devices
• Written word
• What PTs can do
―Be sure to have the Pt’s attention
―Place yourself between 2-3 feet in front of the Pt
―Speak slowly & clearly. Do NOT shout.
―Talk naturally with a slower pace & more pauses
―Lower the pitch of your voice
―Avoid background noise
―Write
J. Blackwood
Vestibular System
Changes
• Disequilibrium and dizziness
• Hair cell receptors decline begins at age 30
• 20% decrease in hair cells of saccule and
utricle
• 40% decrease in hair cells of semicircular
canals
• Vestibular receptor ganglion cells decrease
by age 55-60
PNS Sensory System Changes with
Aging
• Decreased number of unmyelinated and
myelinated nerve fibers
• Blood vessels become atherosclerotic
―Loss of blood supply to nerve fibers
―Major factor of the increased prevalence of
peripheral neuropathies with age
• Sensory conduction velocity slows by 2–4
m/s after age of 20 years
Impairment or Loss of Vibratory Sense
in the Toes and Ankles
• Proprioception impaired very little or not at all
• ↑ thresholds for the perception of cutaneous
stimuli such as touch, tactile sensitivity
―requires refined methods of testing for
detection (e.g. monofilament, 128 Hz tuning
fork)
• Sensory changes correlate with
―loss of sensory fibers on sural nerve biopsy
―↓amplitude of sensory nerve action potentials
―loss of dorsal root ganglion cells
Motor Signs
• ↓ speed and amount of motor activity
• Slowed reaction time
• Impaired fine coordination and agility
• ↓ muscular power
―legs more than arms
―proximal muscles more than distal ones
• Thinness of muscles
―particularly the dorsal interossei, thenar,
anterior tibial muscles, due to a progressive ↓
in the # of anterior horn cells
Changes in Tendon Reflexes
• ↓ Ankle DTR compared to Knee DTR in
persons >70+ years
• Loss of Achilles DTR in people >80+ years
• +Palmomental reflexes in ~50% people >60+
years
―An involuntary contraction of the mentalis
muscle of the chin caused by stimulation of
the thenar eminence.
―Its presence may suggest cerebral pathology
―? sensitivity and specificity
Effects of Aging on Stance and Gait
• Motor agility begins to decline by the 3rd
decade
―decrease in neuromuscular control
―Changes in joints and other structures
• Gait with normal aging
―Steps shorten
―Slower
―Stooping
―More cautious
―Habitually touches (relaying on sensory cues)
Differential Diagnosis of Gait
Abnormalities
• Abnormal gait patterns associated with
degenerative disease of the brain are mostly
accompanied by mental changes
―e.g. frontal lobe–basal ganglionic degeneration,
normal-pressure hydrocephalus
• Other neurologic symptoms and signs
present
Effects of Aging Other Motor
Impairments
• Urinary incontinence
• Compulsive, repetitive movements
―Mouthing, stereotyped grimacing, protrusion of the
tongue, side-to-side or to-and-fro tremor of the head
―Odd vocalizations (sniffing, snorting, and bleating)
―Some of these may resemble tics but they are not
really voluntary
• ↓ forward trunk angular displacement during
stand to sit
―Increased risk of anterior disequilibrium
Dubost 2005
PNS Motor System Changes with
Aging
• Loss of αMN
―remaining αMN will innervate the muscle cells
―remaining MU become larger which can
reduce motor coordination for finely tuned
movements
• Signs of reinnervation
―space between nodes in myelin was reduced
• ↓ in the NCV
• Motor conduction slows by 0.4–1.7 m/s per
decade after 20 years (sensory by 2–4 m/s)
PNS Changes with Aging
• Wallerian degeneration is delayed
• Regeneration takes longer because secretion
of trophic factors is slower than in younger
adults
• Density of regenerated neurons is reduced
• Less collateral sprouting
ANS Changes with Aging
• Sympathetic control of dermal vasculature is
reduced, resulting in reduced wound repair
efficiency
• In aging animal models, TENS improved
vascular response through increasing activity
of sympathetic nerves
Benign Senescent Forgetfulness
• Other terms
―age-associated memory impairment (AAMI)
―minimal cognitive impairment
• Worsens very little or not at all over years
• Does not interfere significantly with work or
ADL
Benign Senescent Forgetfulness
• Diagnostic criteria of AAMI
―age of 50 + years
―a subjective sense of decline in memory
―impaired performance on tests of memory
function (at least one SD below the mean)
―absence of any other signs of dementia
Neurotrophins (neurotrophic factors)
• Proteins secreted by target tissue
―Nerve growth factor (NG), Brain-derived neurotrophic
factor (BDNF), Neurotrophin 3, 4, 5 (NT-3, NT-4, NT5)
• Bind to receptors on cell membranes
• Stimulate neurogenesis
• Induce the survival, development, function of
neurons
• Prolong the life of neurons
• Suppress apoptosis (programmed cell death)
Blesch 2009
Free Radicals and Oxidative Stress
with Aging
• Free radicals can cause oxidative stress in
brain injury and disease and trigger apoptosis
• Enhanced antioxidant status associated with
reduced risk of some NS diseases
• Oxidative stress is a secondary complication
of many progressive NS disorders
―Alzheimer’s Disease
―Parkinson’s Disease
―Amyotrophic Lateral Sclerosis (ALS)
Oxidative stress exists when there is an excess of free radicals over
antioxidant defences. As a consequence, free radicals attack and
oxidise other cell components such as lipids (particularly
polyunsaturated lipids), proteins, and nucleic acids.
Kelly F J Occup Environ Med 2003;60:612-616
Loss of Brain Weight with Aging
• Loss of brain weight correlates roughly with
enlargement of the lateral ventricles and
widening of the sulci
• Possibly due to neuronal degeneration and
replacement gliosis
• Recent research suggests that cerebral cell
loss with aging is LESS PRONOUNCED than
previously thought
• Hippocampal atrophy < 2%/year in healthy
elderly vs. 4-8%/year in Alzheimer’s
Loss of Brain Weight with Age
• Brain shrinkage is accounted for in part by
the reduction in SIZE of large neurons, not
their disappearance.
• Nerve cell shrinkage may be more significant
to function than actual nerve cell loss.
• More substantial reduction in neuronal
number occurs in
―substantia nigra (↓dopamine)
―locus ceruleus (↓ norepinephrine)
―basal forebrain nuclei (↓ acetycholine)
Morphological changes in
cortical pyramidal
neurons during aging
During normal
aging, the
dendritic arbors
and synaptic
contacts of
individual
neurons can
expand
to compensate
for neuronal
loss.
Prolla 2001
Loss of Brain Weight
with Age
• Atrophy of Brain (gyrus)
• Increased size of
ventricles
• Deposit of Lipofuscin in
cells
―6-7% increase by age 90
• Senile plaques and
neurofibrillary tangles
―10% in people age 60 years
―60% in people age 80 years
Loss of Brain Weight with Age
• Loss of neuronal dendrites in the aging
brain
―particularly the horizontal dendrites of the 3rd
and 5th layers of the neocortex.
• Others showed that the surviving neurons
in the neocortex actually exhibit expanded
dendritic trees
―even aging neurons have the capacity to
react to cell loss by developing NEW
SYNAPSES.
Cerebral Atherosclerosis
• In the normotensive, occur in scattered,
discrete plaques
―aorta
―cervical arteries (carotid bifurcation and
higher segments)
―proximal MCA
―vertebrobasilar junction
―basilar portions of the cerebral arterial system
Cerebral Atherosclerosis
• In the hypertensive and diabetic
―more diffuse and extends into finer branches
of the cerebral and cerebellar arteries
• Can be severe in some 30s-40s years old but
absent in some octogenarians!
Loss of Functional Reserve with Aging
• Normally, a significant loss of neural tissue
can occur before functional change occurs
• In older adults, there are less redundant
neurons to take over the function so
functional changes occur more readily