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CHAPTER 2 Physiology of ageing
Sevnaz S¸ahin and Emin Taskiran
Ege University Hospital, Department of Internal Medicine, Division of Geriatrics, Bornova, Izmir, Turkey
Progress in the fight against infectious diseases, improvements in diagnosis and treatment, and technological advances have increased life expectancy at birth. These factors, together with falling birth rates, have meant substantial growth in the proportion of older people in populations worldwide. This has led to a rapid increase in the number of elderly patients encountered by health professionals over the last 50 years. At present, the over‐85 population is the fastest‐growing age group in developing countries. Therefore, health professionals should be aware of the changes that occur in the elderly and should plan treatment accordingly.
Ageing has been defined as a failure to maintain homeostasis under physiological stress. It is a progressive process associated with dysfunction. However, it is not possible to explain and generalize ageing with a single theory. Each elderly individual is unique, and the elderly population is heterogeneous. A 65‐year‐old person may be immobile, while a 90‐year‐old may be mobile and completely independent in their activities of daily living and instrumental activities of daily living. Health professionals in contact with the elderly must take this heterogeneity into account when planning treatment and care.
Theories of ageing can be classified as error theories (stochastic theories) and programmed theories. According to error theories, accumulated damage harms cells and tissues, leading to loss of organ function. Error theories include the wear and tear, free oxygen radicals, mitochondrial DNA, caloric restriction, cross‐linking, and somatic DNA damage.1‐3
Programmed theories include neuroendocrine immunological, cell death, and cellular senescence. According to the neuroendocrine theory, the hypothalamic‐pituitary‐adrenal axis is the most important regulator of ageing. Age‐related atrophy in the thymus, which is responsible for immune system functions, results in decreased production of mature T lymphocytes. Impaired humoral immunity reduces antibody production, and immune suppression increases the risk of infection. An example of programmed ageing is the Hayflick limit.4 Hayflick reported that human fibroblasts in culture stop dividing after 50 cell divisions. Telomeres at the chromosome ends that protect the DNA become shorter with each division until the cell stops dividing. Telomere shortening is the mechanism that protects the cell against uncontrolled division and abnormal growth, at the expense of ageing.5‐7 Apoptosis, or programmed cell death, is responsible for tissue remodelling and homeostasis.
Lopez‐Otin et al. proposed the following hallmarks of ageing, including nine hallmarks grouped into three categories8:
1 Primary hallmarks (causes of damage): Genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis. The primary hallmarks are all negative.
2 Antagonistic hallmarks (responses to damage): Deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence.
3 Integrative hallmarks (culprits of the phenotype): Stem cell exhaustion, altered intercellular communication.
This chapter discusses changes in organs and systems that occur due to the pathogenetic mechanisms identified in the theories of ageing.
The nervous system
The nervous system consists of the central nervous system (CNS), which comprises the brain and spinal cord, and the peripheral nervous system (PNS), which includes both the somatic nervous system (nerves in the peripheral parts of the body) and the autonomic nervous system (ANS). The ANS is further divided into the parasympathetic and sympathetic divisions. Major structures of the brain include the cerebrum, diencephalon (thalamus, hypothalamus, and epithalamus), brainstem (midbrain, pons, and medulla oblongata), and cerebellum.
The nervous system is responsible for regulating body movements, motor and sensory functions, voluntary behaviours, learning, memory, thought, verbal and visual functions, and complex