Taboo #7 – Ageing – Part 2 – Physiology.  

Ageing’s alright, better than the alternative, which is not being here.

In these Covid-19 times it is more important then ever to look after ourselves especially as we age as age is a definite indication for a poorer outcome if one is infected by the Coronavirus and develop Covid-19. The vaccine helps and if two doses are had the chances of developing a debilitating ‘Long-Covid’ condition is far reduced. Let me tell you this is no ‘Kung Flu’, true, many people at any age can ride through this illness without even knowing they’ve had it, however I’ve a friend of 52 with no risk factors who has died and the father of a friend who at 99 has sailed through – it seems impossible to predict who is most at risk other than age, diabetes and immunosuppressive conditions are all risk factors having a negative effect on outcomes. Take the USA for example the population is huge and so even tiny percentages can indicate significant numbers of REAL people. From what I can see 400 or so children have died of Covid-19 and 40,000 have lost a parent – sobering isn’t it when we’re told that the young are not at great risk. 

There are numerous scientific theories on ageing and essentially these fall into two camps. Those that are either due to random external/extrinsic factors (stochastic) involving cumulative cellular damage from free radicals and radiation, errors in protein synthesis, and protein cross-linking or internal/intrinsic (developmental-genetic) causes which hypothesise ageing is related to pre-programmed, genetic controlled cellular ageing. The neuroendocrine and immunologic theory and the concept of ageing genes fit into this latter category.

Cardiovascular – HEART and BLOOD VESSELS – Changes

Physiological changes occur in the cardiovascular system with ageing with a progressive loss of myocytes, the muscle cells of the heart with increase in their volume in an effort to compensate but also increase in their stiffness in both ventricles, the pumping chambers of the heart. This results in reduced efficiency and cardiac failure. In the arterial blood vessels a reduction in elastin in their walls also increases their stiffness and ability to compensate for the normal pressure changes whenever the heart beats. This results in higher blood pressure and atherosclerotic plaque formation which increases the risk of heart attacks (Myocardial Infarction – MI) and stroke (Cerebro Vascular Accident – CVA).

Atherosclerosis is a disease in which plaque made up of fat, cholesterol, calcium and other substances builds up on the arterial wall. Over time, the plaque hardens and narrows the arteries reducing the delivery of oxygen and nutrients to the organs and muscles. This can result in ischaemia, the restriction in blood supply to tissues causing oxygen starvation in the tissues. Cardiac ischaemia results in angina when increased demand for oxygen in the heart muscle during exertion results oxygen starvation and a typical cardiac crushing central chest pain. In the legs this may result in a similar claudication pain in the calves after a certain walking distance.

The resting heart rate does not change significantly as we age, although several conditions may well change the rhythm and this can also increase the risk of MI and CVA. However, the normal maximum heart rate does decrease with age with the maximum that an 85-year-old person can achieve being approximately 70% of that of a 20-year-old and this results in an overall reduction of cardiac reserve as we age.

Respiratory – LUNG – Changes

Normal ageing results in changes in pulmonary mechanics, respiratory muscle strength, gas exchange, and ventilatory control. The respiratory airways, bronchioles and alveolar ducts increase in size particularly after the age of 60 and as the alveoli, the tiny air sacs of the lungs which allow for rapid gaseous exchange, grow the cumulative surface area available for gas exchange decreases by 15% by the age of 70 years. The elasticity of the lungs decreases over time and musculoskeletal changes such as calcification and arthritis of the chest wall joints increases stiffness. These effects combined with weakening intercostal muscles further reduces the ability to breathe efficiently and reduces respiratory reserves.

Renal – KIDNEY – Changes

The kidneys grow from 50 to 250 g in the first 50 years of life but from thereon in decrease to 180g over the next decades. Hypertension, diabetes mellitus, and atherosclerosis accelerate the process of glomerulonephrosis, the non-inflammatory disease of the kidney seen in the non-diseased as they age. This directly affects the Glomerular Filtration Rate (GFR) the test used to assess how well the kidneys are working by estimating how much blood passes through the glomeruli, the tiny filters in the kidneys that filter waste from the blood each minute.

Gastroenterological – GUT – changes

Alterations in normal gastrointestinal physiological features in ageing can be broken down into 3 areas:

1. Changes in neuromuscular function – primarily affect the upper gastrointestinal (GI) tract, particularly the oesophagus leading to conditions such as Gastro Oesophageal Reflux Disease (GORD) with symptoms of ‘heartburn’ and the rarer achalasia which can make it difficult to swallow food and drink.
2. Changes in the absorption and secretion – primarily in small bowel structures. The intestinal villi are the small finger-like projections of tissue which increase the surface area of the intestine and contain specialised cells that transport nutrients into the bloodstream. From about the age of 60 there is a progressive decrease in the height of the villi, with a concomitant decrease in surface area available for absorption. Fibrous connective tissue can also be seen replacing normal tissue making the passage of digested material rather more sluggish.
3. Changes in the structure and functions of the bowel – primarily in the last part of the large bowel are responsible for the most common age-related colonic disorder, Diverticulosis. This occurs when diverticula, small bulging pouches in the bowel wall develop. When one or more of these pouches become inflamed or infected, the condition is called diverticulitis.

Much of the constipation noted in the elderly is thought to be secondary to poor diet. Taste and smell and thus the enjoyment of food may lead to a to a lack of interest in eating. Lack of adequate fluids, often due to concerns around incontinence and convenience food which is often low in fibre combine with a slowing of the bowel transit time to produce smaller, harder, drier and more difficult to pass stool. Lack of exercise, the use of certain drugs to treat various medical conditions and poor bowel habits will also increase the risk

Hepatic – LIVER changes

The size of the liver decreases by up to a third from the age of 50 years. Despite this most liver function test results remain normal in the elderly. However hepatic synthesis of several proteins, including clotting factors, can be reduced, although this does not usually impair baseline function but may explain an increased propensity for bruising etc.

Endocrine – HORMONE – changes

Menopause is characterised by a cessation of menses and a decline in oestrogen levels in females. During the first decade of menopause women undergo rapid bone loss and thereafter a slower phase of continuous bone loss occurs. This decrease in skeletal mass occurs in conjunction with normal age-related bone loss further compounding the problems of osteoporosis and pathological bone fractures in elderly persons. Some bone loss will also result from a decrease in physical activity which is known to help the laying down of new bone.

In addition to its effects on bone, menopause removes oestrogen’s cardio-protective effect increasing overall atherosclerosis plaque formation (above).

Low oestrogen levels experienced in menopause include changes in vasomotor symptoms – Hot Flushes etc, urogenital atrophy (e.g. vaginal dryness and incontinence), increased mood swings as well as a loss of libido. Hormone Replacement Therapy (HRT) can ease these oestrogen-deficient symptoms, although can increase the risk of venous thrombosis, stroke, and breast cancer.

In men testosterone levels reduce with age and this is associated with decreased blood count, muscle atrophy, osteoporosis, libido and possibly erectile dysfunction. However only in older men with markedly low levels has testosterone replacement been shown to improve sexual drive.

The pituitary gland is situated behind the bridge of the nose and is a pea sized brain structure. The pituitary gland produces hormones and releases them into the bloodstream: Those hormones most relevant to the ageing process are:-

FSH and LH which help control the menstrual cycle in women. After the menopause their levels rise dramatically as the feedback mechanism controlling ovarian function becomes inactive as the ovaries stop producing oestrogen. Thyroid Stimulating Hormone (TSH) also works via a feedback mechanism controlling the thyroid’s production of Thyroxine. Thyroid function is not dramatically affected by the ageing process but as time goes by the incidence of auto-immune conditions increases. (See below) The anatomical features and function of the thyroid also undergo age-related changes. However, whether the age-related decline in thyroid function translates to clinical relevance is unclear. Adrenocorticotropic hormone (ATCH), which stimulates the adrenal glands to secrete steroid hormones, principally cortisol. Adrenal function in advanced age leads to changes in the diurnal pattern of cortisol, which shifts earlier in the day and produces higher evening cortisol levels and sleep disturbances manifested by a relatively earlier bedtime and awakening compared with younger individuals. Cortisol is sometimes referred to as the ‘Stress Hormone’ and the attenuated response of body stress can manifest in several ways. For example older individuals have less cutaneous vasoconstriction to cold stimuli compared with younger individuals, making them more susceptible to hypothermia. Growth Hormone (GH) which regulates growth up until adulthood, metabolism and body composition. An age-related decrease in growth hormone may be associated with the decreased lean body and bone mass and increased percentage body fat observed in ageing persons.

For non-diabetic individuals, progressive impairment of glucose tolerance occurs with advancing age, independent of obesity and sex. This age-related decline in glucose handling seems to result from increased insulin resistance rather than an impairment of insulin secretion.

The parathyroid glands the four tiny glands, located in the neck behind the thyroid gland control the body’s calcium levels also undergo age-related changes with increased baseline levels and an augmented response of parathyroid hormone they produce, are also implicated in osteoporosis and bone loss in elderly persons.

Immunological – IMMUNE SYSTEM – changes

Immune function also has an age-related decline. Advanced age leads to a functional impairment and an increased susceptibility to infections. The immune system becomes slower to respond. Autoimmune conditions where the immune system mistakenly attacks and destroys healthy body tissues. There are also fewer immune cells in the body to help healing.

The immune system’s ability to detect and correct cell defects also declines. This can result in an increased risk of malignancy over time.

Neurological – NERVE and BRAIN – changes

Traditional theories of normal neuronal loss with ageing have been challenged with studies of brain specimens from subjects without dementia or other cerebral pathological features showing minimal neuronal loss with normal ageing.

Neurodegenerative processes such as Alzheimer’s and Parkinson’s diseases are strongly associated with neuronal loss.  Cortical atrophy has been repeatedly demonstrated to progress with age with an approximately 10% loss of brain weight in those over 80 as well as brain volume. This is believed to precede neurodegeneration if dementia has not already ensued.  In patients with Alzheimer’s disease up to 25% greater cortical atrophy compared with age-matched control subjects has been noted.

Higher levels of education may protect against dementia. The Cognitive reserve hypothesis suggests a resilience to neuropathological damage. A protective factor may relate to how the brain uses its damaged resources and the ability to optimise or maximise performance through differential recruitment of brain networks and/or alternative cognitive strategies.

Cerebral blood flow and cerebral oxygen consumption have been shown to decrease with age, particularly in areas with decreased grey and white matter. This increases the risk for cerebrovascular accidents with associated vascular disease.

In the eyes the receptor cells of the retina, rods, and cones deteriorate with ageing. Age Related Macular degeneration (AMD) is a common condition that affects the middle part of the vision needed for detailed activities as well as the ability to fully appreciate colour. AMD usually first affects people in their 50’s and 60’s. It doesn’t cause total blindness, but can make everyday activities like reading and reading and writing as well as recognising faces more difficult.

In the ears stiffening of the tympanic membrane (‘ear drum’) and sensory loss of the cochlea are a few examples of changes in the auditory system. Loss of labyrinth hair cells, nerve fibres, and vestibular ganglion cells has been shown to affect the vestibulo-ocular reflex in elderly persons where when rotation of the head is detected compensatory movement of the eyes occurs. Proprioception, the unconscious perception of movement and spatial orientation arising from stimuli within the body itself also diminish with age as does joint motion sensation and sensation of pain. The autonomic nervous system is the part of the nervous system responsible for control of the bodily functions not consciously directed, such as breathing, the heartbeat, and digestive processes. The autonomic neural responses are blunted in elderly persons accounting for such disorders such as orthostatic intolerance or postural hypo-tension when blood pressure falls suddenly when standing up from a lying or sitting position. This marked drop in blood pressure can lead to fainting and possible injury. These effects in part explain some of the excess falls noted in the elderly. Diminished response to pain and touch may also play a big part as well as diminution of vision, hearing and touch.

Thermoregulatory mechanisms become less responsive with age, predisposing elderly persons to hypothermia in cold environments.

As we age we may well be prescribed more and more medications. This ‘Polypharmacy’ is of concern in the elderly since they are at a greater risk of side effects / adverse drug reactions due to metabolic changes and reduced drug clearance associated with ageing. (Drug/Medication clearance is mainly via the liver and kidneys.) This risk is further increased by the number of drugs used and their interactions which can increase or decrease drug blood levels resulting in increased morbidity and mortality.

The 5 Senses also decline with age.

Sight – Pupil size decreases with age making it more difficult to see in dim light. By age 60, pupils may be only one-third of the size they were when 20. Presbyopia – age related long-farsightedness is caused by the loss of elasticity of the lens of the eye and typically occurs middle age. Other conditions include glaucoma, a condition of increased pressure within the eyeball. This can cause gradual loss of sight if not treated, Age Related Macular degeneration (AMD) as mentioned above and diabetic retinopathy in diabetes which is caused by high blood sugar levels damaging the back of the eye (retina). It can cause blindness if left untreated.

Taste – Between the ages of 40 and 50 the number of taste buds decreases and the rest begin to shrink, losing mass vital to their operation. Taste itself is focused on distinguishing chemicals that have sweet, salty, sour, bitter, or umami, (Japanese for “savory”) characteristics. After the age of 60 it becomes more difficult to distinguish different tastes.

Smell – This can slowly deteriorate as the olfactory nerves responsible for smell deteriorate. Diminution of mucus production reduces the amount of time odours stay in the nose and are available to be detected.

Touch – Often, because of reduced circulation to nerve endings the sense of touch declines with age. Pain perception and the ability to distinguish temperature and proprioception are reduced as mentioned above.

Sound – At age 60 one in three adults has some trouble hearing. Causes include long-term exposure to loud noise and deterioration of the nerve cells as discussed above.

This has probably been an over-complicated treatise for most. It is difficult to know where to stop with explanations and definitions. Hopefully it has given an overview and although there are many ageing phenomena that we cannot influence, there are also many that we can. A healthy lifestyle will at least avoid damaging our bodies and accelerate the decline in function. Most conditions and the symptoms and signs relating to these are not necessarily on a linear spectrum, rather that once a threshold is crossed we are subject to the symptoms and signs becoming apparent. Keeping below these thresholds can only be a good thing if we want to avoid becoming unwell mentally or physically.

Q. We all know what to avoid and do more of, however what tips can we share to make this happen?

Q. What is the EVIDENCE for anti-ageing interventions or products, if any?

Q. Do we really want to live ‘forever’ ?

Let me know your feelings, ideas and comments!