Ageing Course Materials

Ageing     Progressive loss of adaptability of an individual organism as time passes; less able to react adaptively to challenges from the external or internal environment. Process that converts young adults, most of them healthy and in no need of assistance from physicians, into older adults whose deteriorating physiological fitness leads to progressively increasing risks of illness and death. The classic picture: o Mild arthritis. o Some loss of hearing acuity. o Some evidence of incipient cataract. o Loss of muscle mass and strength. o Progressive decline in capacity for aerobic exercise. o Troubles with learning and remembering. o Increase vulnerability to infectious illness. Old age is defined as: o Australian aged care services = 70. o Aged pension = 65 (67 in 2023). o WHO = 60 or 65. The ageing population  Overall increase in population.  Reduced birth rates, fertility.  Improved health.  Reduced mortality.  Increased longevity. o Improved sanitation. o Innovations in industrial and agricultural production and distribution. o Advancements in medicine. o New modes of familial, social, economic and political organisation. Theories of ageing  Classical evolutionary theories: o Natural selection does not favour longevity. o Antagonistic pleiotropy (good alleles with bad effects late). o Trade-off between reproduction and lifespan.  Oxidative damage theory: o Free radicals reduce DNA replication and repair.  Hayflick’s phenomenon: o Fibroblasts will divide 50 times in vitro. o Senescence due to telomere shortening.  Observations of animal models: o Laboratory mice or rats fed 30 – 40% less food live up to 40% longer. This seems not to be just due to reduction in obesity, as there were also reduced rates of neoplasia and nonneoplastic disease. o A single gene mutation (e.g. Prop 1) caused low GH, IGF, thyrotropins, thyroxine, prolactin. Affected mice showed a 40 – 50% increase in lifespan. o Caloric restriction and single gene mutations perhaps suggest ageing is a coordinated or unitary process. Normal ageing  Normal ageing vs. age-related diseases.  Relevance and changes in reference ranges.  Small proportion of truly older adults are disease free.  Still, clinically useful to make a distinction. Cardiovascular system  Vascular changes: o Aortic diameter, length and wall thickness increases. o Increased aortic impedance. o Increased arterial wall stiffness. o Increased systolic BP (diastolic BP changes little). o Increased pulse pressure.  Anatomic cardiac changes: o Increased heart weight and left ventricle mass and thickness. o Fibrosis, collagen, amyloid. o LV cavity size decreases. o Valvular degeneration. o Conduction system changes due to loss of sino-atrial node cells (90% at 75) and diminished AV node and distal conduction system.  Physiologic cardiac changes: o Reduced CO, HR and ejection fraction. o LV stiffness and reduced ability for diastolic relaxation. o Decreased cardiac and vascular β-adrenergic responsiveness (examined by isoproterenol, a β-adrenergic agonist).  Clinical significance: o Loss of arterial compliance: isolated systolic hypertension; independent predictor of all-cause mortality and cardiovascular outcomes. o Diastolic heart failure: heart has problem relaxing due to stiffness of LV. CHF with preserved systolic function; increases with age (women > men). o Older patients are less responsive to beta-blockers. Respiratory system  Anatomical respiratory changesL o Lower respiratory muscle strength and endurance. o Stiffer chest wall (less compliant).  Physiologic respiratory changes: o Lower maximal expiratory flows: FEV1, FEV1/FVC. o Increased residual volume, lower vital capacity, but stable total lung capacity. o Lower diffusing capacity (oxygen uptake). o Lower pO2 and SpO2 as a consequence of V/Q mismatch (but no change in pCO2). o Increased lung tissue compliance (loss of lung recoil). o Reduced respiratory drive (for hypoxia, hypercapnia and resistive loads. o Increased airway reactivity (but no change in bronchodilator responsiveness).  Clinical significance: o Patients who have quit smoking will still feel the consequences of ageing more heavily than their non-smoking counterparts. o Especially important in older patients due to their rapidly decreasing FEV1. Neurological system  Anatomical neurological changes: o Loss of nerve cells; glial cell changes. o Decrease in size of the hippocampus, and the frontal and temporal lobes. o Amyloid accumulation (more in Alzheimer’s patients).  Physiological neurological changes: o Decreased number of all receptors. o Remaining receptors are more sensitive (pharmacologic agents are likely to have an exaggerated effect resulting in sedation and adverse drug reactions). o Decreased cerebral blood flow. General intellectual functioning Preserved Crystallised (ability to use skills, knowledge and experience), verbal intelligence. Declining Fluid (think logically, independent on acquired knowledge), non-verbal intelligence, speed of Attention Sustained attention and primary attention span. Executive “Real world” executive function function. Memory Remote memory, procedural memory, semantic recall. Language Comprehension, vocabulary, syntactic abilities. Visuospatial skill Construction, simple copy. Psychomotor  information processing. Divided attention. Novel executive tasks. Learning and recall of new information. Spontaneous word finding, verbal fluency. Mental rotation, complex copy, mental assembly. Reaction time. Changes in spinal cord and peripheral nerves: o Reduced number of nerve cells in the spinal cord. o Nerve conduction velocity slows in peripheral nerves. o Proprioception decreases in the knee, but perhaps not elsewhere in normal ageing. o Decreased vibration sense. Vision  Loss of accommodation (loss of lens flexibility and ciliary muscle tone).  Loss of low-contrast acuity.  Increased sensitivity to glare.  Difficulty adapting to dark.  Loss of colour discrimination.  Loss of attentional visual field.  Reduced visual reading ability.  Decrease in tear production.  Age-related diseases: o Age-related muscular degeneration. o Diabetic retinopathy. o Cataracts. o Glaucoma. o Traumatic brain injury, stroke. o Ptosis due to loose skin; ectropion or entropion. Hearing  Decreased ability to discriminate words or sounds.  High-pitch, high-frequency hearing loss (presbycusis).  Communication techniques: o Face-to-face interaction (for lip reading). o Room free of background noise. o Speaking in a slow and low tone voice.  Age-related diseases: o Ototoxic drugs. o Physical stimulation (excitotoxins, loud noises). Free radicals. o The removal of GFs. o Normal ageing. Muscle  Sarcopenia is age-associated loss of skeletal muscle mass and function.  Very important factor in disability in elderly people.  Muscle erosion begins after the age of 55 years.  40% decline in muscle mass from 20 – 80 years.  Causes of atrophy and loss of skeletal muscle (mainly type II fibres). o Inactivity. o Increased muscle fat. o Insulin resistance. o Loss of alpha motor neurons. o Decreased dietary intake (of proteins). o Increased IL-6. o Loss of oestrogen and androgen. o Decrease growth hormone secretion. Bone    and joints Peak bone density is achieved in the 30s. Resorption/year: females = 1%; males = 0.7%. In normal ageing, there is a decline in cortical thickness of the vertebrae and disruption of the trabecular network. o 4 – 6-fold decrease in vertebral strength. o 2 – 4-fold increase in the risk of vertebral fragility fractures of the spine.  Osteoporosis; osteomalacia.  Age-related changes in cartilage: o Decreased cartilage hydration. o Increased stiffness and cross-linking of collagen. o Reduced numbers and metabolic activity in chondrocytes. o No changes in subchondral bone.  Age-related diseases – osteoarthritis: o Increased hydration. o Decreased collagen. o Chondrocyte proliferation. o Changes in subchondral bone. Skin  Loss of melanocytes.      Decreased sebum secretion. Decreased microvasculature  decreased inflammatory response and wound healing. Decreased sweating and apocrine function. Decrease hair and nail growth. Decrease fibroblasts, and production of collagen and elastin. Renal  Reduced GFR. o Creatinine is also a function of muscle mass. o As people grow older and lose muscle mass, they should have lower creatinine. o However, in diseased states, some elderly patients have high creatinine levels. o Thus, an age standardised GFR must be considered when looking at the elderly.  Reduced numbers of nephrons.  Age-related glomerulosclerosis.  Tubules have impaired concentrating ability and are more at risk of nephrotoxicity.  Reduced RBF. Fluid       balance Decreased total body water. Decreased thirst perception. Impaired renal concentrating and diluting capacity. Increased ADH response to osmotic stimulus. Reduced GFR. Increased risk of hyponatraemia and hypernatraemia. Endocrine system  Normal ageing associated with: o Lower oestrogen and testosterone. o Increased prolactin levels.  Increased insulin levels.  Thyroid stimulating hormone (TSH). o Controversial: TSH levels may increase, decrease or remain stable. o Hypothyroidism: subclinical more common with age; controversy over where normal range should lie. GIT   Reduced connectivity tissue elasticity. Reduced peristalsis and motility  increased risk of constipation, presbyoesophagus.   Reduced liver blood flow and mass. Changes in hepatic endothelium. o Phase I metabolism (oxidation and reduction) reduced. o Phase II metabolism (conjugation) stable. Immune system  Changes in both innate and adaptive immune systems.  Innate immune cells: o Reduced neutrophil and macrophage function. o NK cells increased in number, reduced cytotoxicity.  Adaptive immune system: o Mainly T cells and B cells, with fewer naïve cells. o Lesser immune repertoire. o B cells have reduced antibody response to antigen. Frailty  Clinically recognisable state of increased vulnerability.  Results from ageing-associated decline in reserve and function across multiple physiologic systems.  The ability to cope with every day or acute stressors is compromised.  Clinical definition; needs at least 3 of the following 5 criteria: o Weight loss (≥5% of body weight in last year). o Exhaustion (positive response to questions regarding effort required for activity). o Weakness (decreased grip strength). o Slow walking speed. Decreased physical activity