LITMIR.BIZ

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slight arrhythmias such as premature or skipped beats. If an individual has atrial fibrillation, ventricular filling will be even more impaired. These situations may limit physical performance in elderly people.^23‐24

      Endothelial function plays an important role in the health of vasculature. Beyond its structural role as a barrier between blood and the vascular muscle layer, the endothelium acts as a paracrine tissue by synthesizing nitric oxide (NO) in response to mechanical stimuli. When blood flow increases in the artery, shear stress on the endothelium causes NO production. As a result, NO acts on the vascular muscle layer, causing relaxation and thus arterial dilation via the intracellular cyclic guanosine monophosphate (cGMP) pathway.²⁶ The enzyme responsible for NO production is endothelial NO synthase, which loses its activity with age. The integrity of the endothelium is also essential to avoid endothelial damage. Smoking, obesity, and hypertension lead to endothelial damage, and a high LDL concentration in the blood accumulates in damaged areas, resulting in atheromatous plaque. When this happens in coronary arteries, the atheromatous plaque may lose its integrity and eventually rupture. A thrombotic cascade is triggered, causing a clot in the coronary artery, which results in a myocardial infarction.

      Along with the decrease in NO concentration, atheromatous plaque contributes to arterial stiffness, leading to signs of elevated blood pressure and isolated systolic hypertension clinically.^28‐28 In the end, the compliance ability of the affected vascular segment is compromised, and the artery begins to stiffen. The carotid intima and media thickness increases threefold by age 90.^29‐30 Increases in collagen production, endothelial permeability, and smooth muscle cell infiltration to intima are major mechanisms responsible for increased arterial wall thickness. Regular exercise is a key factor in slowing the stiffening of arteries. Thickening is not specific to arteries but also happens to veins and capillaries. The thickening of veins and valves contributes to reduced venous return to the heart. Slow blood flow in veins facilitates disorders such as deep vein thrombosis, varicose veins, and thrombophlebitis.^31‐32

The endocrine system

In previous decades, the ageing process was thought to be correlated with a decline in hormonal function throughout life. Studies were conducted involving the transplantation of animal endocrine glandular extracts into humans. Then the ageing process was found to be more complicated, although changing hormonal functions do play a significant role. Hormone levels, receptor activities, and endocrine gland functions change with age. Generally, hormone production, clearance rate, and receptor sensitivity decrease. Hormone levels remain nearly the same. Changes in hormone levels are shown in Table 2.2. Detailed alterations are discussed separately below.

      Thyroid

      The blood level of thyroxine remains unchanged as its production and clearance decrease. The triiodothyronine (T3) level decreases because of reduced transformation from thyroxine which results in increased reverse T3.

Table 2.2 Changes in hormone levels with age.

      Source: Morley and McKee³³. © 2017 Elsevier.

Increased	Decreased
Adrenocorticotropic hormone	Growth hormone
Cortisol	Testosterone
Thyroid Stimulating Hormone	Oestrogen
Follicule stimulating hormone, luteinising hormone	Dehydroepiandrosterone sulfate
Arginine‐Vasopressin (daytime)	Arginine‐Vasopressin (nocturnal)
Norepinephrine	Aldosterone

The prevalence of thyroid nodules and thyroid neoplasm increases with age. Ageing is also associated with a tendency for hypothyroidism. Thus, annual TSH level measurement is suggested over the age of 60 even if the person is asymptomatic for hypothyroidism.

      Previous studies suggest that there is a relationship between a mild increase in TSH level and longevity.^34‐35

      Growth hormone

      Growth hormone (GH) decreases with age. A decrease in GH results in a loss of muscle mass and susceptibility to sarcopenia. However, GH replacement was not found to be successful for regaining muscle strength even if it increased muscle mass. In addition, GH replacement was found to be associated with an increase in cardiovascular mortality risk.^36‐37

      Dehydroepiandrosterone (DHEA)

      DHEA and DHEA sulfate levels decrease with age. DHEA decrement was thought to be related to memory and muscle strength impairment. However, studies showed that DHEA replacement had no beneficial effect on either memory or muscle strength in humans. A decrease in DHEA level had only a slight effect on libido, especially in women.³⁸

      Oestrogen

      The oestrogen level decreases dramatically after menopause in women. Most postmenopausal symptoms are related to this oestrogen decrease, such as hot flashes, vaginal dryness and atrophy, and sexual dysfunction. Thus, oestrogen replacement therapy has been widely researched in recent years. The Kronos Early Estrogen Prevention Study (KEEPS) investigated the effects and side effects of oestrogen replacement therapy and showed that it controlled postmenopausal symptoms and had beneficial effects without a serious increase in cardiovascular mortality and venous thromboembolism. Hormonal replacement therapy is not suggested over the age of 60.³⁹

      Testosterone

      The free testosterone level decreases with age because of increased sex hormone binding globulin and increased body fat mass distribution. Muscle mass, strength, frailty, sexual function, and cognition were found to be related to low‐normal testosterone levels. Testosterone replacement therapy was found to have beneficial effects and improve related symptoms in the elderly. Also, testosterone replacement was shown to reverse lower urinary tract symptoms in elderly men.^40‐41

      Hypothalamic‐pituitary‐adrenal (HPA) axis

      HPA axis activity increases with age. Both the morning cortisol peak and continuous cortisol secretion increase with age. The cortisol clearance rate decreases. The cortisol response to exogenously administered dexamethasone and ACTH is blunted in the elderly. Increased body fat composition causes more cortisol conversion from corticosterone. All of these changes result in an increased level of plasma cortisol. An excessive cortisol level causes muscle wasting, dysregulation of blood pressure and glucose, enhanced atherosclerosis, and susceptibility to infections. ACTH and aldosterone production are slightly decreased in the elderly.⁴²

      Sympathetic activity increases with age. Plasma levels of norepinephrine increase, while receptor desensitization occurs. Subsequently, elderly people become prone to a delayed sympathetic response. Postural hypotension is one of the consequences.⁴³

      Arginine‐vasopressin (AVP)

      Daytime release of AVP increases while nocturnal release decreases with age. The nocturnal decrease is responsible for nocturia in older adults.⁴⁴

The gastrointestinal system

      The gastrointestinal (GI) system digests food, absorbs nutrients, and processes them using the

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