by acetylcholine cause contractions in the detrusor muscle, which is controlled by parasympathetic nerves. This mechanism is diminished with age, resulting in less contractility of the detrusor muscle. Sensorial nerve endings remain the same in older adults.66 However, sensorial centres in the brain cortex, which check bladder filling, have diminished activity. In addition, the frontal cortex for processing sensorial input and executing decisions for voiding is impaired with cognitive decline. Also, white matter lesions from microinfarcts may interfere with sensorial input transfer to cortical areas. All of these mechanisms play a role in incontinence in geriatric populations.67
Symptoms related to the lower urinary tract (LUT) include irritability, incontinence, and retention or a feeling of obstruction. The prevalence of these symptoms increases with age; 19% of women and 8% of men older than 65 complain of LUT symptoms.68
Age‐related changes in genital organs
Testicular volume is reduced slightly, while sperm production decreases dramatically with age. Testosterone production from the testes decreases and causes a loss of muscle mass and libido. Prostatic hyperplasia is seen frequently in older men, with a prevalence of one in three men over the age of 70. There are no effective methods for preventing prostatic hyperplasia, but symptom control is key for treatment. An excessively enlarged prostate gland may obstruct the urethra in older men, which is a cause of overflow incontinence.69
The ovaries become atrophic in older women, and cyclic ovulation ends with menopause. Oestrogen production from the ovaries decreases, which has many effects on bones, genitals, and the metabolism. The effects of oestrogen on bones and metabolism are described in other chapters in this edition.
Vaginal prolapse is another issue aggravating LUT symptoms in older women. Vaginal prolapse is related to incontinence and a feeling of irritation. Vaginal dryness and changed flora are important consequences of decreased oestrogen. In addition, endometrial atrophy occurs in the absence of oestrogen with age.70
The immune system
The immune system’s role is to discriminate between self‐antigens and foreign antigens and start a cascade of inflammation via cells and cytokines when necessary to rid the body of foreign antigens. Thus, the immune system is primarily responsible for protecting the body against infections and malignant cells. The immune system consists of inflammatory cells, such as neutrophils, lymphocytes, monocytes, and natural killer (NK) cells; proinflammatory cytokines, such as interleukins and TNF; complement proteins; and immunoglobulins. All of them are triggered or inhibited by the others, and they work in harmony to prevent too much activation or an inadequate immune response. The principal cells managing this cascade are T and B lymphocytes. Immune system cells originate from the bone marrow, peripheral lymphoid tissues, spleen, and liver.
Age‐related changes in the immune system
To help define age‐related changes in the immune system, the term immunosenescence was introduced. The definition of immunosenescence covers all age‐related changes that result in decreased immune functions in the elderly. T cell function is necessary to kill mutated cells by direct cytotoxicity. The mucosal barrier function of the epithelium decreases with age. Thymus hypoplasia occurs, causing less T cell production as well as reduced T cell function. On the other hand, B cell function and number remain nearly stable. Innate immunity is little affected, while adaptive immunity is greatly affected in the elderly. Autoimmunity increases with age, with an excessive proinflammatory state and reduced T cell function playing a role. All of these changes lead to an increased prevalence of infections and malignant disease in the elderly.71
Inflammageing refers to additional immune pathological conditions due to comorbid conditions. The burden of chronic disease increases with age, resulting in a chronic inflammatory state. Excessive cytokine production and activation of B cells, neutrophils, and macrophages mediate this chronic inflammatory state. As a result, oxidative stress and reactive oxygen species (ROS) damage cellular DNA and impair the cell cycle, which may result in a malignant transformation of cells or tissue dysfunction. Inflammageing is one of the key factors affecting the biological ageing of the body and directly affects expected lifespan. It is a target for anti‐ageing research. Lifestyle changes aimed at reducing the incidence, progression, or burden of comorbidities may slow the inflammageing process.72 Some changes in the immune system are shown in Table 2.3.
Table 2.3 Changes in the immune system with age.
| Decreased cell‐mediated immunity |
| Production of lower‐affinity antibodies |
| Increased autoantibodies |
| Decreased delayed‐type hypersensitivity |
| Decreased cell proliferative response to mitogens |
| Atrophy of thymus and loss of thymic hormones |
| Increased IL‐6 |
| Decreased IL‐2 and IL‐2 responsiveness |
| Decreased production of B cells by bone marrow |
| Accumulation of memory T cells (CD‐45) |
| Impaired macrophage function |
| Facilitated production of anti‐idiotype antibodies |
| Increased NK cell number but decreased cytotoxicity |
IL: Interleukin, NK: Natural Killer.
The musculoskeletal system
Structural damage in the musculoskeletal system occurs and causes functional loss in older adults. Osteoporosis and sarcopenia are major issues in older adults and are often accompanied by frailty. Frailty, as a geriatric syndrome, is associated with a higher mortality rate in older adults. Musculoskeletal system changes with age are handled in separate chapters.
Age‐related changes in the skeleton
The most prominent change to the skeletal system with age is calcium loss from bone.74 Bone mass starts to decline gradually after the age of 30. Macroscopically, trabecular bone loss is greater than cortical bone loss. Microscopically, bone mainly consists of an organic matrix and inorganic calcium salts. The balance between osteoblast and osteoclast activity shapes the bone matrix. Osteoblasts produce matrix proteins, mainly type 1 collagen, while osteoclasts resorb old or damaged bone matrix.75‐76 The production‐resorption balance is maintained by Receptor activator of nuclear factor kappa‐b(RANK)RANK ligand interaction. Binding of RANK with RANK ligands results in resorption. Osteoprotegerin is excreted from osteoblasts, which blocks this binding and preserves the intact bone matrix when resorption is unnecessary. Osteoblastic activity decreases while osteoclastic activity increases with age. Calcium salts start to accumulate on the newly synthesized bone matrix. Parathyroid hormone (PTH) and vitamin D are major actors for bone mineralization with calcium by activating or inhibiting osteoclasts. Vitamin D causes mineralization, while PTH causes resorption of calcium from bone. Vitamin D deficiency contributes to calcium loss in older adults.78‐78 Sclerostin, a recently found protein, inhibits the canonical Wnt signalling of osteoblasts. Thus, it blocks osteoblastic bone formation. Sclerostin levels increase with age. In addition, oestrogen decreases in older women, and testosterone decreases in older men, causing a lack of anabolising effect on bone mass.79 All of these mechanisms contribute to osteoporosis pathogenesis. Bisphosphonates and denosumab are drugs that block bone resorption, while teriparatide acts anabolically for new bone synthesis. Antibodies against sclerostin