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Pathy's Principles and Practice of Geriatric Medicine. Группа авторов
Читать онлайн.Название Pathy's Principles and Practice of Geriatric Medicine
Год выпуска 0
isbn 9781119484295
Автор произведения Группа авторов
Жанр Медицина
Издательство John Wiley & Sons Limited
62 62 Furman D, Campisi J, Verdin E, et al. Chronic inflammation in the etiology of disease across the life span. Nat Med. 2019; 25(12):1822–1832.
63 63 Ferrucci L, Fabbri E. Inflammageing: Chronic inflammation in ageing, cardiovascular disease, and frailty. Nat Rev Cardiol. 15(9):505‐522.
64 64 Youm Y‐H, Kanneganti T‐D, Vandanmagsar B, et al. The NLRP3 Inflammasome promotes age‐related thymic demise and immunosenescence. Cell Rep. 2012; 1(1):56–68.
65 65 Youm Y‐H, Grant RW, McCabe LR, et al. Canonical Nlrp3 inflammasome links systemic low‐grade inflammation to functional decline in aging. Cell Metab. 2013; 18(4):519–532.
66 66 Heneka MT, Kummer MP, Stutz A, et al. NLRP3 is activated in Alzheimer’s disease and contributes to pathology in APP/PS1 mice. Nature. 2012; 493(7434):674–678.
67 67 Ridker PM, Everett BM, Thuren T, et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med. 2017; 377(12):1119–1131.
68 68 Ridker PM, MacFadyen JG, Thuren T, et al. Effect of interleukin‐1β inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: exploratory results from a randomised, double‐blind, placebo‐controlled trial. Lancet. 2017; 390(10105):1833–1842.
69 69 Nikolich‐Žugich J. The twilight of immunity: emerging concepts in aging of the immune system. Nat Immunol. 2018; 19(1):10–19.
70 70 Fulop T, Dupuis G, Baehl S, et al. From inflamm‐aging to immune‐paralysis: a slippery slope during aging for immune‐adaptation. Biogerontology. 2016; 17(1):147–157.
71 71 Yager EJ, Ahmed M, Lanzer K, Randall TD, Woodland DL, Blackman MA. Age‐associated decline in T cell repertoire diversity leads to holes in the repertoire and impaired immunity to influenza virus. J Exp Med. 2008; 205(3):711–723.
72 72 Goronzy JJ, Weyand CM. Understanding immunosenescence to improve responses to vaccines. Nat Immunol. 2013; 14(5):428–436.
73 73 Khan N, Shariff N, Cobbold M, et al. Cytomegalovirus seropositivity drives the CD8 T cell repertoire toward greater clonality in healthy elderly individuals. J Immunol Baltim Md 1950. 2002; 169(4):1984–1992.
74 74 Hadrup SR, Strindhall J, Køllgaard T, et al. Longitudinal studies of clonally expanded CD8 T cells reveal a repertoire shrinkage predicting mortality and an increased number of dysfunctional cytomegalovirus‐specific T cells in the very elderly. J Immunol Baltim Md 1950. 2006; 176(4):2645–2653.
75 75 Partridge L, Deelen J, Slagboom PE. Facing up to the global challenges of ageing. Nature. 2018; 561(7721):45–56.
76 76 Newman JC, Sokoloski JL, Robbins PD, et al. Creating the next generation of translational geroscientists. J Am Geriatr Soc. 2019; 67(9):1934–1939.
77 77 Guerville F, De Souto Barreto P, Ader I, et al. Revisiting the hallmarks of aging to identify markers of biological age. J Prev Alzheimers Dis. 2020; 7(1):56–64.
78 78 Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. Lancet. 2013; 381(9868):752–762.
79 79 Cesari M, Araujo de Carvalho I, Amuthavalli Thiyagarajan J, et al. Evidence for the domains supporting the construct of intrinsic capacity. J Gerontol Ser A. 2018; 73(12):1653–1660.
80 80 Duggal NA, Niemiro G, Harridge SDR, Simpson RJ, Lord JM. Can physical activity ameliorate immunosenescence and thereby reduce age‐related multimorbidity? Nat Rev Immunol. 2019; 19(9):563–572.
81 81 Gensous N, Garagnani P, Santoro A, et al. One‐year Mediterranean diet promotes epigenetic rejuvenation with country‐ and sex‐specific effects: a pilot study from the NU‐AGE project. GeroScience. 2020; 42(2):687‐701
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