1. Ageing and changes in brain
Dr Moizuddin Khan
Dr Beenish Mukhtar
اسم ورقم المقرر – Course Name and No.
7/24/2019

2. Learning objectives Define ageing Enumerate theories of ageing
Describe body and brain changes in ageing
Describe memory changes in ageing
Explain carotid hypersensitivity

3. AGEING
It is described as the process that reduces the number of healthy cells in the body, therefore, the body loses its ability to respond to a challenge ( external or internal stresses) to maintain homeostasis.

4. Overview of Some Primary Changes Across Adulthood
Function:
Age of Change:
Nature of Change
Vision
Mid-40’s
Lens thickens, poorer near vision
Hearing
Mid-50’s
Loss of high and low tones
Smell
About 40
Poorer detection and discrimination
Heart & Lungs
35-40
Aerobic capacity during work
Height 40
Compression of disks in spine
Skin
Wrinkling, oil secretion poorer
Bones 35
Loss of calcium, osteoporosis – increased porosity

5. The Two Main Aging Theory Categories
Programmed Theories
Aging has a biological timetable or internal biological clock.
Error Theories
Aging is a result of internal or external assaults that damage cells or organs so they can no longer function properly.
Many theories are a combination of programmed and error theories.

6. Error Theories Programmed Theories Programmed Senescence Theory
Endocrine Theory
Immunology Theory
Wear and Tear Theory
Rate-of-Living Theory
Cross-linking Theory
Free Radical Theory
Error Catastrophe Theory
Somatic Mutation Theory

7. Programmed Senescence Theory
The result of sequential switching “off” or “on” of specific genes.
Example – “Hayflick’s Limits”
Fibroblasts removed from umbilical cord & cultured.Fibroblasts divide and repeated until ~ 50 divisions .Will not divide past this point
2. Endocrine Theory
Biological clocks act through hormones to control the pace of aging. Hormones effects growth, metabolism, temperature, inflammation and stress.
Examples- Menopause -Decreased level of estrogen & progesterone

8. 3. Immunologic Theory
A programmed decline in the immune system leads to an increased vulnerability to disease, aging and death
Example- Decreased T cells (helper cells) in adults
Increased diseases in older adults
Increased autoimmune diseases in adults

9. Wear and Tear Theory
Years of damage to cells, tissues and organs eventually wears them out, killing both them and the body
Example- Wearing out of the skeletal system such as in osteoarthritis
Wear and tear can be viewed as a result of aging and not the cause of it.

10. 2. Rate-of-Living Theory
The greater an organism’s basal metabolic rate, the shorter the life span.
Free radicals or other metabolic by-products play a role in senesce.
Example
Animals with the most rapid metabolisms tend to have the shortest lifespans, i.e, birds have a shorter lifespan than humans.
Studies examining the relationship between metabolic rates and longevity have produced inconsistent results, limiting the usefulness of this theory.

11. 3. Cross-Linking Theory
The accumulation of cross-linked proteins damages cells and tissue, slowing down bodily processes.
Example
Non-enzymatic glycosylation reactions occur when glucose molecules attach to proteins causing a chain of chemical reactions resulting in a structural change to the proteins.
Loss of flexibility of connective tissue
Microvascular changes in arteries

12. 4. Free Radical Theory The most acceptable theory for ageing.
A free radical is a molecule with an unpaired, highly reactive electron.
One type of very reactive free radical is the oxygen free radical, which may be produced during metabolism or as a result of environmental pollution
Hydroxyl ion z one of the most damaging free radical

13. Free Radical Theory
The free radical “grabs” a electron from any molecule in its vicinity.
It does this because electrons like to exist in pairs.
When it “grabs” an electron from another molecule, it damages the other molecule.

14. Free Radical Theory
Free radicals may damage Molecules like are fats, proteins, and DNA (both in the nucleus and in mitochondria).
If membrane fats are attacked -breakdown of the cell membrane. If it is a red blood cell membrane, then hemolysis.
If proteins are attacked, - breakdown of proteins, may result in the loss of biological function and the accumulation of “catastrophic” compounds.
If DNA is attacked- mutation may cause aging or cancer.

15. Free Radical Theory
Free radicals do not go unchecked. The body has a multi-layred defense system that reacts and detoxifies the damaging radicals.
Defenses include:
Natural antioxidants in the body, such as bilirubin.
Enzymes such as superoxide dismutase (SOD), catalase, & glutathione peroxidase.
Dietary antioxidants such as beta carotene, and the vitamins C and E.
The free radical theory of aging proposes that, little-by-little, small amounts of damage accumulate and contribute to deterioration of tissues and organs.

16. 5. Catastrophe Theory
Any damage to the enzyme systems that synthesize proteins in the body results in faulty protein synthesis.
The faulty proteins continue to accumulate in the cell until they reach a level that damages the cells, tissues, and organ
When enough damage accumulates, this may result in cell malfunctioning ( aging) leading to death.

17. 6. Somatic Mutation
Genetic mutations occur and accumulate with age in the somatic cell causing the cell to:
Deteriorate
Malfunction
Accumulation of mutations result in :
Damage to the DNA
The theory states that aging is an imbalance between DNA’s ability to repair itself and accumulating DNA damage.
When the damage exceeds the repair, the cell malfunctions and this can lead to senesence.

18. SKIN & NAILS Atrophic changes in sweat glands
Thickened fingernails & toenails
Generalized loss of body hair and head hair
Decrease in the functioning pigment-producing cells-->graying
Some remaining pigment cells enlarge--> “age spots”
Skin changes increase. vulnerability to infections/disorders
Loss of subcutaneous fat
> vulnerability to pressure sores
less insulation of body to cold (also affected by diminished blood flow to skin & extremities) & heat

19. Musculoskeletal changes
Osteopenia --> Osteoporosis:
Gradual loss of bone that reduces skeletal mass without disrupting the proportions of minerals & organic materials
Bones most critically involved: vertebra, wrist, hip
Osteoarthritis ( Degenerative joint disease)
A gradual wearing away of joint cartilage that results in the exposure of rough underlying bone ends
Can damage to internal ligaments
Most commonly associated with weight bearing
Sarcopenia:
Loss of muscle mass that occurs with aging

20. Changes in Brain Overall weight loss = 5%
Some loss of neurons, but new ones can grow and new synapses can form too
Substantial loss of dendrites leads to some slowing at synapses – one of the key markers of aging
Changes in some neurotransmitters – loss in dopamine and acetylcholine,
Most of these changes more marked with disease!

21. Neurologic Changes in Aging
Physiologic changes Clinical correlation
loss of neuron & subdural hematoma after brain weight trivial head injury
impaired auto regulation ↓ brain blood flow
↓ dendritic connections impaired memory retrieve
short term memory loss ↑interview time
↓ dopamine activity ↑Parkinsonism
↑ neurofibrillary tangle pathologic change of
& senile plaques Alzheimer disease
↓ acetylcholine activity ↑amnesia

22. Neurologic Changes in Aging
Physiologic changes Clinical correlation
↓ serotonin activity :↑depression
change of sleep :unnecessary narcotic pattern drug
change of :↑sensitivity to pharmacodynamics benzodiazepines
slow central processing :↓ intelligence
& reaction time

23. Peripheral Nervous System Changes in Aging
Physiologic changes Clinical correlation
↓ vibratory sense esp interpretation of
feet neuropathy
↓ thermal sensitivity ↑ injury esp.men
↓ size of large ↓propioceptive & myelinated fiber vibratory sense
↓ two-point impaired use of
discrimination test fine instrument

24. Ageing and memory Causes of low retention with age:-
“Disuse” view -which states that memory strategies are used less by older adults as they move further away from the educational system.
“memory self-efficacy,” view -older people do not have confidence in their own memory performances, leading to poor consequences..
Inability to suppress irrelevant information in working memory, thus the capacity of relevant information is limited
“Diminished attentional capacity” hypothesis, older people engage less in self-initiated encoding due to reduced attentional capacity

25. Alzheimer's disease (AD),
Referred to simply as Alzheimer's, is a chronic neurodegenerative disea se that usually starts slowly and worsens over time It is the cause of 60% to 70% of cases of dementia. The most common early symptom is difficulty in remembering recent events (short-term memory loss)

26. GASTROINTESTINAL SYSTEM
Atrophy of secretion mechanisms
Decreasing motility of the gut
Loss of strength/tone of muscular tissue & supporting structures
Changes in neurosensory feedback
Enzyme & hormone release
Innervation of the tract
Diminished response to pain & internal sensations

27. CARDOPULMONARY SYSTEM
In the absence of disease, the heart tends to maintain its size
Heart valves tend to increase in thickness with age
BP tends to go up with age
Systolic stabilizes at about age 75
Diastolic stabilizes at about 65 then may gradually decline

28. Atherosclerosis vs. Arteriosclerosis
A narrowing of arterial passageways as a result of the development of plaques on their interior walls
Reduces the size of the passageway--even to the point of closing it off. A cause of ischemic heart tissue (tissue deprived of adequate blood supply)
Arteriosclerosis:
A generic term referring to the loss of elasticity of arterial walls
Often referred to as “hardening of the arteries”

29. Carotid sinus hypersensitivity
Carotid sinus hypersensitivity (CSH) is an exaggerated response to carotid sinus baroreceptor stimulation.
It results in dizziness or syncope from transient diminished cerebral perfusion.
Although baroreceptor function usually diminishes with age, some people experience hypersensitive carotid baroreflexes.
For these individuals, even mild stimulation to the neck results in marked bradycardia and a drop in blood pressure

30. CSH predominantly affects older males
CSH predominantly affects older males. It is a potent contributory factor and a potentially treatable cause of unexplained falls and neurocardiogenic syncopal episodes in elderly people. Yet, CSH is often overlooked in the differential diagnosis of presyncope and syncope
اسم ورقم المقرر – Course Name and No.
7/24/2019

31. Respiratory Changes
Airways & tissues become less elastic & more rigid with age
Osteoporosis may alter the size/shape of the chest cavity
Power of respiratory & abdominal muscles becomes reduced-- hinders diaphramatic movement
All parameters are reduced, Only the lung compliance increases due to loss of lung elasticity

32. URINARY SYSTEM
“The bladder of an elderly person has a capacity of less than half (250ml) that of a young adult (600 ml) and often contains as much as 100 ml of residual urine”.
Micturition reflex is delayed-- usually activated when bladder is half full

33. Female genital tract External genitalia Folds become less pronounced
Skin becomes thinner
Vascularity & elasticity decrease
Becomes more susceptible to tissue trauma & itching
Number of glands decrease, as does level of secretion
Internal reproductive organs
Uterus decreases in size & becomes more fibrous
Uterus has fewer endometrial glands
Cervix reduced in size
Uterine tubes become thinner
Ovaries take on an irreguar shape
Ovulation stops--menopause
(50% between ages 45 and 50)

34. Male Genital System
Continues to produce germ cells (sperm) and sex hormones (testosterone) well into old age, declining with advancing age
Size & firmness of the testes decrease
Reduced sperm production due to age-related fibrosis which constricts the blood supply
Fibrosis may also affect the penis since erection is a purely vascular phenomenon

35. Thank you for your excellent attention