1. How is each system affected by aging?
   1. Digestive System
      1. Decrease in glandular secretions --> drier mouth
      2. Atrophy of muscous membrane affecting absorption
      3. Weaker sphincter contractions
         1. caused by changes in protein synthesis in muscle cells
         2. caused by decline in control of contraction
      4. Weaker smooth muscle contractions --> slower peristalsis
   2. Nervous System
      1. Gross structural changes
         1. decrease in synaptic density
         2. decrease in nerve cell body size
         3. no decrease in mean neuron number
         4. decrease in glial cell numbers
         5. 11% decrease in brain weight from age 65-80
         6. 6% decrease in bran size from 65-80
      2. Microscopic structural changes
         1. decrease in number of dendrites
         2. decrease in number of dendritic spines
         3. accumulation of autofluorescent pigment (ie. lipofuscin)
      3. Mental ability changes
         1. short term memory declines
         2. personality is maintained
         3. vocab increases until 80, then declines slightly
      4. Sensory system changes
         1. Taste
            1. not affected by age
            2. no loss of taste buds or receptors
            3. affected by lack of vitamins though --> poor nutrition --> common in the elderly
         2. Touch
            1. decrease in sensitivity of hand only
            2. only 2 of 5 touch receptors are affected (Meissner's and Pacinian)
         3. Smell
            1. decrease in detection/identification of odors from age 60
            2. males have greater loss than females
         4. Hearing
            1. decrease in sensitivity to high frequency tones
         5. Vision
            1. decrease in curvature of cornea
            2. increase in stiffness of lens
            3. decrease in transparency of lens
      5. Pathologies
         1. Alzheimer's disease
         2. Bi-polar disorder
         3. Schizophrenia
         4. Parkinson's disease
   3. Reproductive System
      1. Men --> ANDROPAUSE
         1. decrease in mean testosterone levels
            1. possibly "use it or lose it" --> less sex, less testosterone
         2. loss of circadian rhythm in testosterone production (as seen in younger men)
         3. increased LH levels
         4. decrease in normal motile sperm
         5. increase in sperm density
         6. erectile dysfunction (changes in vascular system and signal transduction)
      2. Women --> MENOPAUSE
         1. decrease in estrogen and ovarian hormones
            1. vaginal dryness
            2. hot flashes
            3. dryness of the skin
            4. increase in LDL, decrease in HDL
            5. increase in alpha-beta plaque formation --> increased risk of Alzheimer's
            6. increase in calcium reabsorption --> development of weak bones --> fractures
         2. eventual follicular deficiency (not necessarily at menopause)
   4. Endocrine System
      1. Hormonal changes
         1. insulin resistance --> affects hormone sensitivity --> causes hyperinsulinemia, hyper glycemia, obesity, type II diabetes, formation of AGEs
         2. decrease in antidiuretic hormone receptors --> decreased water reabsorption --> causes decreased blood volume, lower blood pressure, dizziness, falls
         3. declined beta-adrenergic receptor function --> poor sympathetic control --> affects blood pressure, maximal heart rate, stroke volume, cardiac output --> less able to do physical activity
         4. decreased estrogen --> causes menopausal changes, osteoporosis (increased calcium reabsorption), cognitive decline
         5. decreased testosterone --> causes muscle weakness, male osteoporosis
         6. reduced melatonin secretion --> causes changes in circadian rhythms, sleep, and anti-oxidant protection
      2. Increased vulnerability to Type II diabetes
         1. rate that blood glucose level returns to normal after glucose overload reduced
         2. caused by decrease in sensitivity of nonhepatic tissue to insulin
         3. require twice as much insulin as younger people to achieve a certain level of glucose uptake
   5. Integumentary and Immune Systems
      1. Wrinkles
         1. loss of elasticity
         2. disorganization of fibres
      2. Accumulation of UV damage
         1. premature aging if extensive exposure
         2. collagenase expression
      3. Thinning of skin
         1. males have thicker dermis than females
      4. Atrophy of hypodermal layer (hands and face predominantly)
         1. thermoregulation abilities compromised
      5. Free radical production
         1. free radical production exceeds removal --> redox imbalance --> prostaglandin production --> more free radical production
      6. Reactive nitrogen species production
      7. Growths
      8. Pigmentation
      9. Cancer
      10. Dermal papillae density decreased
      11. Shrinking of thymus
          1. less thymus hormones --> less mature T-lymphocytes --> compromised immune function
      12. Decrease in DNA repair
      13. Deterioration of the immune cells of Langerhans in skin
          1. decrease in immune defense
      14. skin more vulnerable to mechanical damage and infections
   6. Muscular System
      1. Decreased sphincter functioning leading to urinary/fecal incontinence
      2. Muscle atrophy if physically inactive
         1. SOME age-related decrease in muscle mass but mostly activity related
         2. fast twitch fibres decrease in muscle fibre size and number
         3. slow twitch fibres decrease in muscle fibre number only
      3. Difference between slow and fast twitch fibres decreases
      4. Sarcopenia
      5. High risk of tendon tearing because of increased stiffness
   7. Cardiovascular System
      1. Decrease arterial wall elasticity
         1. systolic hypertension
         2. increased pulse pressure
      2. Loss of myocytes
      3. Beta-adrenergic receptor decline
      4. Decreased sympathetic reactivity of blood vessel/cardiac tissue
      5. Increased fibrosis of heart structure
      6. Apoptosis of sino-atrial node cells
         1. affects heart rate
      7. Endothelium cells damaged faster than repaired
         1. could develop lesions
      8. Increase in cardiac lipofuscin (autofluorescent pigment)
      9. 30% increase in thickness of left ventricular wall
         1. hypertrophy
      10. Pathologies
          1. Atherosclerosis
   8. Urinary System
      1. Decrease in blood volume
         1. causes decrease in blood pressure --> dizziness --> falls
      2. Decrease in blood vessels and loss of normal (functioning) glomeruli
         1. causes decrease in cortex size --> decrease in kidney mass
      3. Decrease in filtration and reabsorption rates
         1. causes decrease in concentration of urine
         2. causes increase in water loss
         3. combined with fewer functioning nephrons, causes longer response time to reestablish equilibrium when stressed
      4. Decrease in anti-diuretic hormone receptors
      5. Decrease in blood flow (10% per decade after 40 years)
      6. Compression of urethra in men due to hypertrophy of prostate
      7. Decrease in creatinine clearance
      8. Pathologies
         1. Urinary incontinence
         2. Nocturia
         3. Prostate cancer
   9. Respiratory System
      1. Collagen cross-linking causing a decrease in elasticity of lungs and thorax
         1. means more rigid thorax --> more work to breathe --> decreased efficiency of ventilation --> increased respiration rate
      2. Total lung capacity remains the same
      3. Decreased maximal VO2 ability
      4. Pathologies
         1. Pulmonary emphysemia
         2. Pneumonia
         3. Chronic bronchitis
   10. Skeletal System
       1. Loss of equilibrium between osteoclasts and osteoblasts
          1. affected by...
             1. calcitonin
             2. weight-bearing exercise
             3. calcium
             4. growth hormone
             5. vitamin D
             6. estrogen and gonadal hormones
             7. parathyroid hormone
       2. Loss of cartilage translucency
       3. More brittle cartilage due to calcification
          1. nutrients and waste can't diffuse properly --> cells die --> reabsorption --> cartilage becomes bone
   11. Limbic System
       1. Stress
          1. 3 stress reactions:
             1. limbic system stimulates hypothalamus --> pituitary gland secretes ACTH --> adrenal cortex secretes cortisone
             2. increased risk of lesions
             3. limbic system stimulates hypothalamus --> balance changes between sympathetic and parasympathetic divisions --> shifts metabolic energy balance --> energy production decreases --> fatigue and insomnia increase
             4. immune system is hindered --> increased vulnerability to infection, lesions, cancer & overproduction of immune cytokines
          2. Many reasons for stress in old age:
             1. change in occupation
             2. more frequent death of friends/family
             3. change in family dynamics
             4. social isolation
             5. diminished self-image
             6. new environment
2. Why is healthy aging important?
   1. Because there is a greying of society
      1. Why?
         1. Decline in fertility rates
         2. Better health care system
         3. Better sanitation
         4. Increased emphasis on healthy living
         5. More knowledge about disease prevention/treatment
         6. Baby boom
   2. Limit burden on health care system and tax payers
      1. Seniors would need less medical attention
      2. People would take less time off work due to decreased morbidity
   3. Improve quality of life
3. How is healthy aging measured?
   1. Demographics
      1. Morbidity
      2. Mortality
      3. Gender differences
   2. Survival curves
      1. Rectangularization
   3. Life tables
   4. Compression of morbidity
4. What are the theories of aging?
   1. Neuroendocrine immune theory
      1. Hypothalamus acts as a pace-maker and defects in its performance cause changes in the control of the endocrine, autonomic, and immune systems. Hypothalamus is responsible for many important body functions, such as thermoregulation, and declines in its function can make them less effective.
   2. Free-radical theory
      1. Free radicals, which can cause damage to cells, are not removed as quickly as they are created so damage is able to accumulate and cause functional deficits.
         1. Examples of negative effects
            1. Decrease in insulin sensitivity due to defective cell receptors (damaged by free radicals)
            2. Lower sympathetic nervous control because of decline in beta-adrenergic receptor sensitivity (damaged by free radicals)
         2. Aging interventions
            1. Calorie restriction (in rats): decreases proton motive force resulting in decrease in production of free radicals (by-products of ETC)
            2. Anti-oxidants: protect mitochondria against free radicals
   3. Telomere length theory
      1. During every act of transcription small sequences of the telomere are lost and eventually they reach a critical length where cell replication is no longer possible and the cell dies. This will cause a decline in cell proliferation and organs such as the mucous membranes and skin will be negatively affected.
         1. Causal or marker of another mechanism?
         2. Explanation for telomere loss in oxygen solution?
   4. Cross-linking theory
      1. Over time reactive carbonyl sugars and the amino groups of proteins interact through a series of rxns to form advanced glycation end-products (AGEs) which bind macromolecules together and have deleterious effects of the protein's function (usually decrease in elasticity).
         1. Schiff base --> Amadori product --> AGEs --> accumulate in long-lived proteins --> interfere with normal functioning
         2. Examples of negative effects
            1. Cross-links bind collagen fibrils in connective tissue of blood vessels by forming links between the collagen helices. Causes loss of elasticity, increased brittleness, increased resistance to enzymatic breakdown and therefore, increased systemic blood pressure, decreased diastolic pressure, and increased pulse pressure.
            2. Accumulation of AGE adducts in the lens result in cross-linking that increases stiffness and decreases lens' ability to refract light properly.
   5. Wear and tear theory
      1. Some body structures are irreplaceable so over time damage builds up and leads to loss of function or apoptosis.
         1. Small damage in DNA occurs regularly and if the repair mechanisms can't keep up it can have widespread consequences
         2. Examples
            1. Osteoarthritis
   6. DNA as biological clock theory
      1. DNA has the ability to determine timing of apoptosis which would, if enough cells died, affect function.
5. How is healthy aging researched?
   1. Types of studies
      1. Longitudinal
         1. Advantages
            1. Disadvantages
         2. reliable data
            1. expensive
         3. data can be reconstructed into cross-sectional style
            1. time consuming
         4. age effects and period effects get confused
      2. Cross-sectional
         1. Advantages
            1. Disadvantages
         2. cost-effective
            1. less reliable data than longitudinal
         3. fast
            1. environmental changes affect age cohorts differently
      3. In vitro cell/tissue cultures
         1. Advantages
            1. Disadvantages
         2. no harm to animals (or limited)
            1. rxns different in vitro vs. in vivo
         3. cost effective
            1. hard to interpret results
         4. can simplify system and focus on certain part only
      4. Animal experiments
         1. Advantages
            1. Disadvantages
         2. environment similar to humans
            1. animals have different responses than humans
         3. permission to perform experiments not allowed on humans
            1. ethics issues
         4. expensive (care of animals and monitoring)
   2. Examples of studies
      1. Baltimore Longitudinal Study of Aging
         1. collected data over two 20 year periods to make conclusions about the impact of age on physiology
      2. Louis-Camille Maillard, 1912
         1. provided crucial research necessary to develop the cross-linking theory of aging
6. What is healthy aging?
   1. Aging in general
      1. Morbidity vs. mortality
         1. Morbidity ratios refer to the presence of illness in a population. Mortality defines the ratio of deaths.
      2. Chronological age vs. physiological age
         1. Chronological age is the time (usually in years) since the birth of the organism. Physiological age uses not time but changes in important physiological variables to measure age.
      3. Intrinsic factors of aging
         1. Changes in genetics
         2. Changes in homeostatic control
         3. Decreased synthesis of collagen
      4. Extrinsic factors of aging
         1. Smoking
         2. Diet
         3. Occupation
         4. Environment
   2. Increase in mean lifespan not maximum
   3. Avoidance of age associated diseases
      1. Age-dependent
         1. Osteoporosis
         2. Alzheimer's disease
            1. What happens?
            2. abundance of neurofibrillary tangles in anterior temporal lobe
            3. ventricular system enlarged
            4. atrophy of neocortex
            5. neuritic plaques
            6. amyloid angiopathy
            7. eventual synaptic loss and neurotransmitter defects
         3. Type II diabetes
            1. What happens?
            2. target cells in nonhepatic tissues lose ability to respond appropriately to insulin
            3. slower insulin clearance
            4. Risk factors
            5. environmental factors
            6. genetic predisposition
            7. sedentary lifestyle
            8. Symptoms
            9. Decline in growth hormone, antidiuretic hormone, and sexual steroids
            10. skeletal muscle loss/reduced muscle strength
            11. male impotence
            12. decreased sensation in hands and feet
            13. blurred sight
         4. Osteoarthritis
            1. What happens?
            2. gradual degeneration of joint cartilage
            3. development of osteophytes
            4. Risk factors
            5. age
            6. genetic predisposition
            7. obesity
            8. trauma to joint
            9. diabetes
            10. excessive load on joints
         5. Cataracts
      2. Age-related
         1. Urinary incontinence
            1. What happens?
            2. increased cross-linking and loss of elasticity in the bladder wall
            3. decreased muscle sphincter control
            4. Symptoms
            5. urinary leak
         2. Colon cancer
         3. Lung cancer
         4. Atherosclerosis
            1. What happens?
            2. intima drastically thicken due to macrophage/smooth muscle lesions, narrowing arteries to critical limit
            3. Risk factors
            4. age
            5. environmental factors
            6. Symptoms
            7. heart attack
            8. sudden cardiac death
            9. stroke
            10. angina
         5. Pulmonary emphysema
            1. What happens?
            2. increase in mucous production
            3. decreased elasticity decreases effectiveness of inspiration and expiration
            4. hypoxemia
            5. increased residual volume
            6. Risk factors
            7. age
            8. environmental
            9. smoking
            10. air pollution
      3. Intercurrent
         1. Pneumonia
      4. Wear and tear
         1. Presbycusis
         2. Myocardial infarction
   4. Holistic model
      1. Biological perspective
      2. Historical perspective
      3. Sociological perspective
      4. Political perspective
      5. Psychological perspective
   5. Compression of morbidity
   6. Disease prevention
7. How do we age successfully?
   1. Physical activity
      1. Can induce fourfold increase in growth hormone
      2. improves immune system
      3. protects brain from age related decline
      4. improves homeostatic control mechanisms
      5. improves metabolism and sleep
      6. improves mood
      7. weight bearing exercises before menopause to improve bone mass
   2. Good nutrition
      1. low-fat
      2. limited alcohol
      3. limited caffeine
      4. high vegetable intake
      5. limited red meat
      6. Mediterranean-type diet
      7. nutritionally balanced diet and avoid obesity
   3. Interventions if necessary (not for normal aging)
      1. Reproductive system
         1. Growth hormone supplementation/replacement
         2. DHEA administration
            1. might improve feelings of wellbeing
         3. Estrogen replacement therapy
            1. decrease in production of free radicals
   4. Stress coping
      1. social support
      2. religion/meditation
      3. exercise
      4. hobbies