Physiological/Biological/Physical Changes with Ageing

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Physiological/Biological/Physical Changes with Ageing

All body tissues and organs undergo changes with increased age. Ageing is not a disease, but a natural process with most morbidity in older persons being due to disease and not age related changes. These declines in physiological or biological function do not define ageing (as it does not incorporate social aspects). Some of the changes may not be due to ageing, but may be due to inactivity.

Senescence – the process of physical decline.

Generalised changes with ageing include :
• a decrease in the rate of mitosis in tissue composed of cells that regenerate (eg epithelial tissue)
• a deterioration of the more specialised nondividing cells (eg neurons and skeletal muscle cells) leading to decreased functional capacity
• changes in connective tissue leading to increased rigidity and loss of elasticity  changes in most organs

Body dimension and composition changes:
• peak height is reached around 16-29 years for females and 25-29 years for males  then decreases slowly. Females decline > males due to higher prevalence of osteoporosis. Most of decline due to compression of the cartilaginous discs in vertebral column
• on average weight declines from age 70 in females and 40 in males
• percent of total body water decreases linearly with age
• muscle mass declines and body fat increases
• bone loss increases with age
• decrease in basal metabolic rate

Connective tissue changes

The molecular stability of collagen increases with aging due to decreased reducibility of crosslinks between adjacent tropocollagen increased number of crosslinks (cross linking theory of ageing)  structures that are composed of collagen become less compliant. Molecular movement of waste products and nutrients is impaired. Water content is decreased. There is also an increase in the diameter and number of collagen fibres. These can restrict the tissue mobility of structures that are composed of collagen.
Rate of ageing of collagen is about 3x greater in those who smoke.

The amount of elastin in skin and large arteries decreases with ageing. The elastin crosslinks become more stable – like collagen. It becomes less distensible and can undergo fragmentation

Production and release of the glycoproteins decrease with age  reduction in fluid content of connective tissues

Problems associated with connective changes with ageing:
fibrinous adhesions – exudation of fibrinogen into tissue spaces is not ‘broken down’ as easily as it is in younger people  produces adhesions  limits movement of surrounding tissues.
contractures in collagen structures – elastic component of collagen is progressively reduced, most likely due to increased cross linking of collagen as part of maturation process.
less ease of movement of connective tissues
decrease in maximum length at which tendons and ligaments rupture

Affects of connective changes in the foot:
Decrease strength of ligaments:
• eg decrease in strength of spring ligament may increase the risk for a flat or pronated foot and for posterior tibial dysfunction
eg changes in the intermetatarsal ligament  foot ‘splays’

Alterations in plantar heel fat pad:
• decreased resistance to compression
• distortion and rupture of fibrous tissue strands
• thicker elastic fibres
• older people tend to have thicker but more compressible fat pads  risk factor for heel pain

Skin changes

Many changes occur to the skin and its appendages with increased age. The changes are due to the two processes of intrinsic changes with age and the extrinsic process of photoaging (photoaging is superimposed on the intrinsic ageing).

thins due to flattening of dermal-epidermal interface with a decrease in the number and size of rete pegs/interdigitations (diminished nutrient transfer from dermis and greater risk of epidermal and dermal separation)
weaker dermal-epidermal interface (greater risk of blistering)
basal keratinocytes become shorter and fatter
spinous keratinocytes become smaller
decrease in filaggrin (protein that binds keratin filaments into macrofibrils)
decreased keratohyaline granules in stratum granulosum
decreased water content in stratum corneum
less epidermal turnover (declines up to 50% from age 30 to 80)
reduction in melanocytes (declines up to 20% per decade) ( increased vulnerability to UV radiation)
decline in vitamin D production
reduction in Langerhan’s cells (change in immunological status)

• reduction in thickness due to collagen and elastic fibre loss (up to 20% - greater in areas of photodamage)
• decrease in tensile strength and pliability
• large decrease in number of capillary loops (decreased vascularity); flattening of the dermal-epidermal junction
• dermal blood flow declines up to 60%
• vascular responses are impaired ( impaired inflammatory response, reduced capacity to clear antigens and impaired thermoregulation)
• increased dilation and porosity of capillaries  leakage
• increase in the dilation of lymphatic channels
• decrease in fibroblasts and mast cells

Volume of subcutaneous fat declines ( skin wrinkling, decreased shock absorption and impaired thermoregulation)

sebaceous glands increase in size or stay the same. Output is decreased
decrease in number of eccrine sweat glands and in output ( increased risk of heat stroke)
reduction in number of hair follicles; hair grays in 50% from loss of melanocytes;
nail growth rate decreases; nails become more brittle; lunula is less well defined; may be thicker – the changes are due to age related changes in the vascular nail bed and germinal matrix; other nail changes may be apparent due to history of trauma or presence of a disease process
loose about 30% of sensory nerve end organs between ages 10 and 90 ( reduction in light touch and vibration sensation)

Bone changes

Increased inactivity associated with ageing  less mechanical stress for stimulation of new bone formation  less bone mass per unit volume. With increased age, there is a greater absorption of bone compared to formation of bone (the ratio of formation to resorption is ‘uncoupled’). Less density and mass  weakens bone  could progress to clinical osteoporosis if uncoupling ratio is high. Females affected more and at faster rate than males. After age 30, density in males decreases about 0.5% year. In females – 0.5% per year up to age 50 an after age 65. Between 50 and 65  up to 3% per year.

Osteocytes undergo degenerative changes – reduced RNA production; reduced protein synthesis; reduced mitochondrial activity. Osteoclasts don’t seem to be affected greatly by ageing (or activity may be increased).

Bone marrow changes:
The space occupied by haematopoietic tissue declines from birth until age 30, then remains stable – begins to decline again about age 70. The number of stem cells decreases with age. Erythropoiesis is slower with increasing age.

Joint changes

Three considerations when looking at joint changes associated with age :
changes in structure and function of joint connective tissue may occur simply as a natural process of growing old
the type and degree of physical activity one engages in also have a significant influence on the structure and function of joint connective tissues
pathology can affect the joint’s connective tissue at any age and lead to profound functional limitation and disability

With increased age cartilage becomes hypocellular and has a decrease in elasticity. Degeneration and an increase in fibrillation of joint cartilage occurs from about age 30 onwards – due to reduced ability of chrondoblasts to secrete glycoproteins. Chrondrocytes increase in size and secrete increased amounts of lysosomal enzymes. The proteoglycan subunits become smaller and water content decreases  reduced elasticity of cartilage  increased risk for damage. The proportion of keratin sulfate increases. Hyaluronic acid secretion is reduced  reduced lubrication  more heat and friction during movement. These changes increase the risk for osteoarthritis.

Muscle changes

Gradual decreases occur in muscle strength until about age 60, then they become more rapid. Changes may be related to aging or may be related to decreased physical activity. Changes are also dependent on changes in other body systems (nervous, vascular and endocrine).

Histological changes with ageing:
loss of fluid and inorganic salts
changes in enzyme activity
reduction in contractile proteins
decreased in oxidative capacity
decreased capillary density

Muscle mass as a proportion of body weight decreases from 45% at age 20 to 25% age 70  may account for most of changes in maximum strength – decrease is due to a sarcopenia (a decreased synthesis of muscle proteins). The reduction occurs in both fast and slow twitch fibres – both size and number, but faster contracting (type 2) fibres decrease to a greater extent.

Pattern of strength reduction varies depending on type of muscle contraction – greatest reduction occur for concentric contractions and least reduction is for eccentric contraction  activities that involve lengthening of muscle are less affected.

Those who have chronic diseases, immobility or disability  at greater risk of deconditioning and accelerated loss of muscle mass (disuse atrophy/hypokinetic disease)  need for early physical therapy intervention. Strength training in older adults can have significant effects on the changes related to ageing – increase in fibre size; increased capacity for lactic acid levels; increase in resting levels of ATP; increased activity of anaerobic enzyme function; improved physical performance.

In lower limb:
• decrease in strength and power (more pronounced than in upper limb)
muscles fatigue more quickly
ankle plantarflexion strength in 70 yr old is 20% of that of a 20 yr old (may be activity rather than age related)
increased risk for injury
muscle weakness may be related to falls

Neurological changes

Intellectual performance (in the absence of disease) is generally maintained until at least 80 years of age, but tasks can take longer to perform due to a slowing in central processing.

In CNS  reduced rate of cerebral spinal fluid production; increased size of ventricles; decreased weight and volume of brain (not uniform- greater in frontal and temporal lobes); gyral atrophy; decreased cerebral blood flow; decrease in synthesis of neurotransmitters; neuron loss in subcortical regions; deterioration in volume and mass of myelin; lipofuscin accumulates in cells (significance of this not clear).

Most recent evidence has shown that there is not a loss of cortical neurons with ageing – previous research that showed this was limited by investigation techniques . There is a loss or neurons associated with dementia.

Increased reaction times; slowness of psychomotor speed; delayed central processing; slowed transmission of motor impulses – most changes due to deterioration in myelin.

Vibration perception thresholds increase with age – also get a reduced perception to touch, proprioception and pressure sensation (assumed to be due to reduction in density and sensitivity of sensory end organs in skin).

Posture & Gait Changes

The trunk shortens due to thinning of intervertebral discs – loss is about 1.2cm in height every 20 years from age 50 onwards with a large individual variability.

Gait changes in older persons are due to - slower reaction times; poorer vision; decreases in muscle strength; decreases in speed of movement; decreases in aerobic endurance; decreases in sensory input; decreases in joint ranges of motion

Gait changes with ageing:
• decreased velocity – mainly due to reduced step length rather than cadence; after age 70, velocity declines about 15%-20% per decade (slowness of gait may also be a voluntary change due to preference and not wholly related to age related changes)
• cadence does not change with age
• velocity is significantly related to hip and knee flexion ranges ; kinematic alterations at the hip are a cause of reduced gait speed
• less power generated during propulsive phase
• less ankle joint motion (more flexed at contact)
• less knee extension during swing phase (more flexed at heel contact)
• less toe clearance  increased risk of tripping over objects  falls
• increased duration of double limb support during gait; changes from about 18-20% in younger people to up to 30% in the healthy old
• may have increased base of gait  these changes have the affect of a “safer”, more stable gait pattern

Balance declines with age, due to combination of effects of impairments of the visual, vestibular, somatosensory and musculoskeletal system. Adaptations to postural perturbance occur at a slower rate in those that are older  greater risk of falling.

Cardiovascular and respiratory system changes

The body depends on these two system to perform physical work  declines occur in exercise capacity, but adequate for function at rest.

Ageing has significant impacts on the cardiovascular system:
heart size decreases slightly, left ventricular wall thickens (heart size may increase in congestive heart failure or other heart diseases)
cardiac output decreases about 1% a year after age 30 (but is still adequate for normal daily activities)
cardiac reserve decreases
resting heart rate does not change much, but maximal heart rate decreases
amyloid and lipofuscin deposits
collagen and fat content increase and elastic content decreases in heart muscle
heart valves become stiffer and thicker  compromise cardiac function and may exacerbate any pre-existing valve disorder
less sensitive to beta-adrenergic stimulation
more fibrosis of SA node and conduction cells and decrease in number of pacemaker cells  decrease in conduction (may become abnormal  dysarhythmia)
increase in both systolic and diastolic blood pressure
vessels become calcified; decreased elastin in vessel walls; arteries become less distensible; vessels become more tortuous
peripheral resistance increases
reduced capacity for exercise
postural hypotension
the age related changes to the cardiovascular system become most noticeable when unusual or increased demands are placed on the heart

Peripheral blood changes:
Levels of haemoglobin and haematocrit values decrease slightly with age (but usually remain within normal adult range).
Other peripheral blood values do not appear to change with age.

Respiratory system changes:
• less vital capacity with increased residual volume (decreases by 50% by age 90)
• reduced oxygen diffusing capacity (peaks in early 20’s, then progressively declines)
• decline in elastic recoil decreased airflow at low lung volumes
• decline in partial pressure of oxygen (PaO2)
• decrease in alveolar size
• rigidity of rib cage and thoracic muscles due to musculoskeletal changes
• decreased responsiveness of central and peripheral chemoreceptors and their integration in the CNS
• decreased effectiveness of mucociliary clearance ( may increase risk for respiratory infections)
• decreased cough reflex

These respiratory system changes result in an increased risk for breathlessness, sleep disorders and less ability to fight infections (eg pneumonia).

Immune system changes

A number of progressive dysfunctional changes occur in the immune system that increases the chance of infection and the ability of antibodies to recognise self from non-self ( higher incidence of autoimmune diseases and cancer). Immune responses are delayed – this is also complicated by the ability to cope with the stress of an infection. Immune senescence has been implicated in a number of age related changes (immunological theory of ageing).

Specific changes in the immune system/response (modified after Miller , 1996):
Germinal centre:
decreased processing of immune complexes
decreased number of dendritic cells
decreased Ig hypermutation

B Lymphocytes:
decreased number of circulating and antigen responsive B cells
decreased affinity maturation
increased repertoire degeneracy
decreased idiotype focusing

T Lymphocytes:
Changes in T cells are responsible for most of the changes in the immune response.
• increased memory, CD8+ & CD28- T cells
• decreased naive T cells
• decreased IL-2 production
• decreased IL-2 receptors
• decreased protein kinase signals

Other system changes

Gastrointestinal tract changes:
dental problems  affect ability to chew food  affects nutritional status; salivary glands secrete less ptyalin and amylase and becomes more alkaline; taste sensation decreases
decreased saliva production; muscles of mastication weaker & trophic changes in jaw; sense of smell declines
oesophageal peristalsis is weaker; oesophageal motion becomes uncoordinated; decrease in gastric emptying; decrease in vascular perfusion of GI tract; decreased motor function and muscle tone of colon; depression of the defaecation reflex (increases risk for constipation)
aging related changes tend to have minimal effect on GI function, due to large functional reserve capacity
increased prevalence of drug induced GI disorders
small decrease in pancreatic enzymes; deposition of amyloid in islets of Langerhans
liver decreases in size; reduced blood flow; fall in glycogen stores; decline in hepatic drug metabolism

Renal & urinary changes:
• renal function declines significantly with age, but it is sufficient for normal function until a response is needed to pathologic or physiologic stress and the impairment then becomes noticeable
• basement membrane in kidneys thicken; medullary connective tissue increase and replaces interstitial cells; renal blood vessel walls undergo sclerosis (smaller vessels appear to be spared)
• renal blood flow decreases (from around 1200ml/min at age 30 to 600ml/min at age 80);
• decrease in glomerular filtration rate, decrease in rate of tubular secretion and decrease in number of nephrons  decrease in renal capacity (a 70 year old, in absence of disease, has 40-50% reduction in renal function)
• kidney mass declines (decreases 20% between ages 30 and 70)
• renal changes affect drug elimination from the body  dosage adjustments
• basal renin levels decline by up to 50%  risk of fluid and electrolyte imbalances
• urinary changes include a loss in muscle tone; capacity decreases; decrease in maximal urethral closure; increase in postvoiding volume (incomplete emptying); changed patterns in excretion of fluid – majority of excretion tends to occur at night (nocturia)

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