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 are under investigation for use in osteoporosis medication.
Cartilage changes also occur in older adults. Although mechanical stress on joint cartilage over the years causes damage, older adults who had sedentary lives suffer from cartilage deformation in big joints due to inactivity. Deformation of the cartilaginous tissue of intervertebral discs causes a reduction in height in older adults. The water, type 2 collagen, elastin, and hyaluronic acid content of cartilage tissue decrease with age as well.80 Tendons become weaker and lose resistance against power with age. A decrease in water content, along with elastin and collagen destruction, are responsible for tendon damage with age.81
Age‐related changes in the muscles
Peak muscle mass volume is achieved by 25 years from birth and is related to exercise and protein intake. After age 25, humans begin to gradually lose muscle mass and strength until the end of life. Sex steroids, testosterone and oestrogen, which decrease with age, contribute to muscle mass by their anabolic effect, in addition to nutrition and exercise. Skeletal muscle consists of muscle fibres, which are grouped into muscle cells. Muscle cells are rich in proteins like actin and myosin that form motor units. Muscle function depends on a motor unit structure, calcium, and ATP. Any impairment in one of these results in functional loss.82
Muscle mass and muscle strength decrease with age because of the loss of motor units and muscle fibres. In addition, reduced protein synthesis causes muscle atrophy.83 Muscle mass and muscle strength loss are defined as sarcopenia in older adults. Sarcopenia, as a geriatric syndrome, is related to frailty and mortality. Sarcopenia makes older adults more dependent and causes falls and fractures. The only way to prevent the progression of sarcopenia is to exercise regularly and have an adequate diet. Sarcopenia is diagnosed by European Working Group on Sarcopenia in Older People (EWGSOP) 2018 criteria as follows84:
1 Low muscle strength
2 Low muscle quantity or quality
3 Low physical performance
If criterion 1 is present, probable sarcopenia can be diagnosed. If criteria 1 and 2 are present, sarcopenia can be diagnosed. And in the presence of all three, severe sarcopenia is diagnosed.
In the EWGSOP 2018 report, handgrip strength is measured using a hand dynamometer. Cut‐off levels for defining low muscle strength are <27 kg for men and <16 kg for women. Muscle quantity is measured by bioimpedance analysis. Appendicular muscle mass values of <20 kg for men and <15 kg for women are considered low muscle mass. Physical performance is measured by gait speed. A gait speed value of <8 m/s is considered to be low physical performance. Additional measurement methods for each of the criteria are described in detail in the EWGSOP 2018 report.
The respiratory system
The respiratory system starts with the nose, continues along the pharynx, larynx, trachea, and bronchi, and ends with the alveoli in the lungs. Oxygenation of blood and carbon dioxide release, the primary duties of the respiratory system, occur in the alveoli of the lungs. Oxygenated haemoglobin in red blood cells supplies oxygen to tissues and binds carbon dioxide in return to release it to the air via the alveoli.
The maximum capacity of the lung is achieved in young adulthood; subsequently, both capacity and lung function start to decline. The respiratory reserve is closely associated with achieving maximum lung capacity; therefore, elderly people can face respiratory difficulties even with normal age.85 Since the respiratory system is directly open to the atmosphere, it is very susceptible to harm from air pollutants, chemicals, and smoke.86‐87 Over the course of a lifetime, exposure to these pollutants causes age‐related changes in the respiratory system in addition to intrinsic ageing mechanisms.
Age‐related changes in the respiratory system
With age, mucus glands decrease in large airways, thus reducing mucus production. Tracheal cartilage becomes ossified and stiff, and bronchial cilia movement reduces with age. Vocal cord elasticity is impaired with age, making the voice thinner and harder to project. Small airway changes in the ageing lung include loss of elastic recoil, reduced lung compliance, increased fibrosis of lung parenchyma, and loss of alveolar surface area. Collagen and elastin structures are impaired with age, leading to alveoli and alveolar duct enlargement. Enlargement of these small airways causes easy collapse during expiration, causing senile emphysema.88‐89 Lung compliance (chest wall compliance) decreases with age because of degenerated intervertebral disks, kyphosis, ossified cartilage ribs, weak respiratory muscles, and sarcopenia. This causes a decrease in forced vital capacity (FVC), which is a sign of restrictive pathology. Along with the destruction of small airways and weakness in the diaphragm and intercostal muscles, forced expiratory volume in 1 second (FEV1) also decreases with age. The FEV1/FVC ratio decreases, as the reduction in FEV1 is more prominent than the reduction in FVC, leading to a pattern of obstructive pathology. Residual volume (RV) increases due to decreased elastic recoil and decreased chest wall compliance.90‐91
Older people tend to breathe more deeply, which demands excessive respiratory muscle performance. The total lung capacity (TLC) does not change significantly with age. Structural changes in lung parenchyma result in an impaired capacity to diffuse oxygen more so than is the case for carbon dioxide, leading to a lower arterial partial pressure of oxygen without resulting in desaturation of haemoglobin. An impaired response to the sympathetic nervous system is seen in the respiratory system as well as the cardiovascular system, resulting in bronchoconstriction, hypoxia, and delayed acceleration of respiratory rate with stress such as exercise. In addition, the coughing reflex is impaired in the elderly. As a result, aspiration of food into the airway and related complications (like pneumonia) are more commonly experienced with age.92 Decreased mucus secretion impairs the immune defence system of the respiratory system, further predisposing elderly people to lung infections.
Cigarette smoke is the primary extrinsic factor causing parenchymal damage of the lungs. Smoking causes inflammation, immune response, and oxidative damage to the alveoli epithelium. Cigarette smoke also leads to increased vascular permeability; neutrophils migration to the alveolar interstitium; production of proinflammatory cytokines like IL1, IL6, and TNF alpha; exaggerated immune response; increased metalloproteinase activity; and degraded collagen and elastin in the alveoli interstitium, eventually resulting in alveolar structural damage. Lymphocytes and NK cells contribute to these damaging mechanisms as well. Impaired elastic recoil and decreased alveolar surface are the main properties of emphysema triggered by smoking. In addition, mucociliary clearance of chemicals is impaired with smoking. Tobacco is responsible for 50% of laryngeal and lung cancers.93‐95
The skin
The
