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

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

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.

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

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.

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

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

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

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.

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.

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

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

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.

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.

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.

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.

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.

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

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

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!

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

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

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

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

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)

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

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

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”

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

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

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

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

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)

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

Thank you for your excellent attention