Previous authors: Marjorie A. Maddox, EdD, MSN, ARNP, ANP-C, and Holly Evans Madison, RN, MS. Theories of aging have been debated since the time of the ancient Greeks. Autoimmun. Environ. Disease or not, aging is easily treatable. Hypotheses 144:110015. doi: 10.1016/j.mehy.2020.110015, Fuellen, G., Liesenfeld, O., Kowald, A., Barrantes, I., Bastian, M., Simm, A., et al. In nervous and muscle tissue, to which free radicals have a high affinity, a substance called lipofuscin has been found and is thought to be indicative of chronologic age. BMC Med. Interactions between gerontologic nurses and older adults are not limited to a specific disease or physiologic process, absolute developmental tasks, or psychosocial changes. The term immunosenescence has been given to this age-related decrease in function. J. Gerontol. Antiox. Biophys. Therefore an eclectic approach provides an excellent foundation as nurses plan high-quality care for older adults. Res. Pharmacol. The results of this landmark study changed the way scientists viewed the biologic aging process. The end result is that tissues do not function at optimum efficiency (Hayflick, 1996). 17, 679–690. 1:e2. Based on the conclusions of this experiment, the Hayflick Limit Theory is sometimes called the “Biologic Clock,” “Cellular Aging,” or “Genetic Theory.” The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease. July 23, 2018studentBusinessFrailty and Sarcopenia Would you classify telomere-based aging as stochastic or non-stochastic Several years ago, researchers discovered a part of the nuclear chromosome called a telomere. (2020). Basis Dis. This results in an increased incidence of cancer in older adults. Changes occur in the immune system, specifically in the T lymphocytes, as a result of aging. doi: 10.18632/aging.103493, Bonkowski, M. S., and Sinclair, D. A. Ageing Res. Akaberi, D., Krambrich, J., Ling, J., Luni, C., Hedenstierna, G., Järhult, J. D., et al. doi: 10.1016/j.yjmcc.2015.01.021, Drucker, D. J. Nat. Although these molecules do not contain DNA themselves, they can cause mutations in the DNA–RNA transcription, thereby producing mutations of the original protein. An interesting aspect of the 1961 study was that freezing was found to halt the biologic cellular clock (Hayflick & Moorehead, 1961). The skin of a baby is soft and pliable, whereas aging skin loses much of its suppleness and elasticity. Spermidine supplementation and voluntary activity differentially affect obesity-related structural changes in the mouse lung. Does eNOS derived nitric oxide protect the young from severe COVID-19 complications? At the physiological whole-body level, metformin improves glucose tolerance. Kowald, A., and Kirkwood, T. B. Weight loss-dependent and -independent effects of moderate calorie restriction on endothelial cell markers in obesity. Neuroendocrine Control or Pacemaker Theory. Immun. Cerani suggests increased levels of blood glucose cause increased amounts of cross-linking, which accelerate lens, kidney, and blood vessel diseases (Schneider, 1992). Aging 12, 9959–9981. More research needs to be performed regarding the safety and efficacy of melatonin. doi: 10.1101/2020.04.15.20066548, Barja, G. (2014). Thus, the endothelium is a unique diffuse organ distributed throughout all other organs and tissues and capable of responding to stimuli in coherent ways despite all local peculiarities. Rev. Animal research has demonstrated that administration of antioxidants did increase the average length of life, possibly because of the delayed appearance of diseases that may have eventually killed the animals studied. Navaratnarajah, A., and Jackson, S. H. D. (2017). Metabolic health and lifestyle medicine should be a cornerstone of future pandemic preparedness. The decreasing function of an organism may lead to a complete failure of either an organ or an entire system (Hayflick, 1996; In recent years the theory has not been supported by research. Toxicol. Previous authors: Marjorie A. Maddox, EdD, MSN, ARNP, ANP-C, and Holly Evans Madison, RN, MS Microbes Infect. (Stochastic Biological Theory) These studies also found that rodents fed supplementary melatonin restricted their calorie intake. May polyphenols have a role against coronavirus infection? There are two aspects in the adverse effects of excess blood glucose. This study contradicted earlier studies by Carrel and Ebeling in which chick embryo cells were kept alive indefinitely in a laboratory; the conclusion from this 1912 experiment was that cells do not wear out but continue to function normally forever. The process that increases the risk of dying with increasing time of living is known as aging. Other deleterious results are related to free radical molecules in the body. The two regression lines in Figure 1B that are based on COVID-19-attributed mortality data normalized against the registered COVID-19 cases (CFR) appear virtually identical. (2020). Increased energy demands are associated with increased generation of ADP. Research has shown there are complex interactions between the endocrine and the nervous systems. Rep. 3, 51–67. By incorporating a holistic approach to the care of older adults, nurses can view this ever-increasing portion of the population more comprehensively. Hassan, S. M., Jawad, M. J., Ahjel, S. W., Singh, R. B., Singh, J., Awad, S. M., et al. Approaches to understanding aging may be categorized into those that treat it either as resulting from the accumulation of stochastically damaged macromolecules, or as a programmed process. Saunders), 33–41. 9:1417. doi: 10.3390/jcm9051417, Sassi, F., Tamone, C., and D’Amelio, P. (2018). 32, 44–55. Two developments are occurring at this time in relationship to DNA and the aging process. Front. Its effects converge onto its ability to inhibit the protein complex mTORC1 directly and/or via inhibiting the kinase Akt, a component of the signaling pathway from insulin to mTORC1 via the protein complex TSC. Res. An open question: is it rational to inhibit the mTOR-dependent pathway as COVID-19 therapy? Wear and Tear Theory Aging and coronavirus: exploring complementary therapies to avoid inflammatory overload. Metformin enhances autophagy and normalizes mitochondrial function to alleviate aging-associated inflammation. These highly reactive free radicals react with molecules in cell membranes, in particular, cell membranes of unsaturated lipids such as mitochondria, lysosomes, and nuclear membranes. Neuroendocrine Control or Pacemaker Theory (2020). Develop nursing interventions based on the psychosocial issues and biologic changes associated with older adulthood. With all uncertainties and discordances, one consensus is that aging compromises the ability of the endothelium to respond to increased blood pressure and flow rate by increasing the production of nitric oxide (⋅NO). 69, 825–839. Endothelial cell senescence in aging-related vascular dysfunction. Neuroendocrine-ontogenetic mechanism of aging: toward an integrated theory of aging. Sports Exerc. Clin. doi: 10.1016/j.socscimed.2020.112906, Santín-Márquez, R., Alarcón-Aguilar, A., López-Diazguerrero, N. E., Chondrogianni, N., and Königsberg, M. (2019). Figure 1. 88:107001. doi: 10.1016/j.intimp.2020.107001, Pan, H., and Finkel, T. (2017). doi: 10.1134/s2079057019010065, Golubev, A. G., and Anisimov, V. N. (2019). The prevention and management of COVID-19: seeking a practical and timely solution. Diabetes and metabolic syndrome as risk factors for COVID-19. The prospects for specific vaccines against SARS-CoV-2 and/or effective therapies for COVID-19 to be developed soon are currently uncertain. Antioxidants also appear to have an effect on the decline of the immune system and on degenerative neurologic diseases, both of which affect morbidity and mortality (Hayflick, 1996; Weinert & Timiras, 2003; Yu, 1998, 1993). However, the ubiquitous presence and abundance of glucose make its role as a source of endogenous damage comparable with that attributed to ROS. Lipofuscin, a lipid- and protein-enriched pigmented material, has been found to accumulate in older adults’ tissues, and is commonly referred to as “age spots.” As the lipofuscin’s presence increases, healthy tissue is slowly deprived of oxygen and nutrient supply. Aird, W. C. (2013). (2014) focused on the age-associated decrease in the sensitivity of platelets to the anti-aggregation effects of ⋅NO, thus highlighting another rationale, besides decreased ⋅NO production, for proposal to use ⋅NO donors or stimulants of ⋅NO production in therapy for COVID-19 (Williams et al., 2020; Yamasaki, 2020). Medicine, 45, 6–10. This list also includes several pulmonary pathologies, which are, notably, specific for the physiological system that is the most vulnerable to COVID-19. Fasting blood glucose at admission is an independent predictor for 28-day mortality in patients with COVID-19 without previous diagnosis of diabetes: a multi-centre retrospective study. This effect occurs even in persons with chronic limiting states such as rheumatoid arthritis. When this theory was first proposed in 1882 by Weisman, death was seen as a result of tissues being worn out because they could not rejuvenate themselves in an endless manner (Hayflick, 1988). The cross-linkage theory of aging hypothesizes that with age some proteins become increasingly cross-linked or enmeshed and may impede metabolic processes by obstructing the passage of nutrients and wastes between the intracellular and extracellular compartments. (2020). Why the endothelium? The pursuit of the first of the objectives proved to be largely futile (Aune et al., 2018; Jenkins et al., 2018). PLoS One 15:e0235458. Physical exercise as a tool to help the immune system against COVID-19: an integrative review of the current literature. Hipkiss, A. R., Baye, E., and de Courten, B. 21, 183–203. Both T and B lymphocytes may respond to an invasion of the organism, although one may provide more protection in certain situations. Reactive carbonyl species scavengers – novel therapeutic approaches for chronic diseases. Supplemental vitamins and minerals for CVD prevention and treatment. Non-steroidal anti-inflammatory drugs in management of COVID-19: a systematic review on current evidence. It appears that the female reproductive system is governed not by the ovaries or the pituitary gland but by the hypothalamus. Metabolic Theory of Aging/Caloric Restriction (2016). The resulting increase in AMP serves as another, besides NAD+, signal of energy deficit, in this case resulting from increased demands rather than from decreased supply. Melatonin has been found to be a regulator of biologic rhythms and a powerful antioxidant that may enhance immune function. [Epub ahead of print]. Melatonin is produced by the pineal gland, the function of which was a mystery until recently. Can. This study contradicted earlier studies by Carrel and Ebeling in which chick embryo cells were kept alive indefinitely in a laboratory; the conclusion from this 1912 experiment was that cells do not wear out but continue to function normally forever. Rev. Therefore the mitochondria, for example, can no longer function as efficiently, and their cell membranes may become damaged, which results in increased permeability. Sports Exerc. An interesting aspect of the 1961 study was that freezing was found to halt the biologic cellular clock (Hayflick & Moorehead, 1961). doi: 10.1007/978-981-13-3681-2_13, Pollán, M., Pérez-Gómez, B., Pastor-Barriuso, R., Oteo, J., Hernán, M. A., Pérez-Olmeda, M., et al. The changes that occur with aging are most apparent in the T lymphocytes, although changes also occur in the functioning capabilities of B lymphocytes. Petrov National Medical Research Center of Oncology, Saint Petersburg, Russia. Rev. As to COVID-19 pathophysiology, reduced glucose tolerance is a hallmark of poor metabolic fitness manifested in obesity and hyperlipidemia. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The next transcription would again contain an error. Arch. Hill, T. R., Granic, A., and Aspray, T. J. NAD+ is increasingly recognized as not only the coenzyme of dehydrogenases but also as the central component of the biochemical system implicated in sensing deficits of energy resources and transducing the respective signal to downstream effectors. Vitamins C and E are two of these substances and can inhibit the functioning of the free radicals or possibly decrease their production in the body. The recognition of the universal truths is what we attempt to discover through the theories of aging. As to ⋅NO production, the abilities to ameliorate the age-associated functional impairments of the endothelium have been demonstrated for all agents featured in Figure 3: metformin (Triggle et al., 2020), resveratrol and other polyphenols (Oak et al., 2018; Li et al., 2019), NAR (Mateuszuk et al., 2020), sulforafan (Matsui et al., 2016), carnosine (Takahashi et al., 2009), antioxidants (Wray et al., 2012), spermidine (Ahrendt et al., 2020), melatonin (Rodella et al., 2013; Salmanoglu et al., 2016), and rapamycin, the effects of the latter being controversial (Reineke et al., 2015). In the chemical terms, glucose is not unique in this regard. For the purpose of this manuscript, the indexersAlzheimer,aging,Alzheimer, andaging were considered;theories of aging were researched. Wear and Tear Theories This theory proposes that each time your DNA replicates, certain factors such as radiation, chemical reactions, or mutations cause "agents" to attach to the newly formed DNA strands. All the information, content and live chat provided on the site is intended to be for informational purposes only, and not a substitute for professional or medical advice. Biologic theories are concerned with answering basic questions regarding the physiologic processes that occur in all living organisms as they chronologically age. doi: 10.1073/pnas.1511085112, Yousefifard, M., Zali, A., Zarghi, A., Madani Neishaboori, A., Hosseini, M., and Safari, S. (2020). 9, 1–14. Dietary intake and blood concentrations of antioxidants and the risk of cardiovascular disease, total cancer, and all-cause mortality: a systematic review and dose-response meta-analysis of prospective studies. DTs related to mortality attributed to COVID-19 in the general population (Figure 1A) are smaller. Notably, the risk of COVID-19 complications and associated deaths is increased upon reduced glucose tolerance even in non-diabetic patients (Drucker, 2020; Huang et al., 2020; Marhl et al., 2020; Zhu et al., 2020; Wang et al., 2020). Scientists are studying the roles that the hypothalamus and the hormones DHEA (dehydroepiandrosterone) and melatonin play in the aging process (Guardiola-Lemaitre, 1997; Two developments are occurring at this time in relationship to DNA and the aging process. Rep. 7, 768–771. These people were trying to equate humans with the marvelous machines they were producing. Some research supports a combination of exercise and dietary restrictions in helping to inhibit the cross-linkage process, as well as the use of vitamin C prophylactically as an antioxidant agent (Bjorkstein, 1976). Ser. Although they differ, both viewpoints agree that, in the end, the cells in the body become disorganized or chaotic and are no longer able to replicate, and cells die. Stochastic studies of aging and mortality in multicellular organisms. Other theories are the result of ongoing advances made in biotechnology and, as such, provide glimpses into our future. Sci. Potential mechanisms underlying cardiovascular protection by polyphenols: role of the endothelium. J. Mol. Social relationships and physiological determinants of longevity across the human life span. (2020). Proc. Med. Each of the drugs appears to reproduce only a part of the physiological responses to reduced resource availability caused by either dietary calories restriction or physical activity promotion, which are the most robust means of mitigating the adverse manifestations of aging. doi: 10.1016/s0074-7742(08)60107-5, Dominski, F. H., and Brandt, R. (2020). Tags: Gerontologic Nursing Front. (2018). This deficiency is most evident in people with type II diabetes, obesity, metabolic syndrome, hypertension, and other conditions known to increase the risk of COVID-19 complications. Both T and B lymphocytes may respond to an invasion of the organism, although one may provide more protection in certain situations. The raw data supporting the conclusions of this article can be found in the following public database: https://www.mortality.org/cgi-bin/hmd/country.php?cntr=NLD&level=1. These changes include a decrease in humoral immune response, often predisposing older adults to (1) decreased resistance to a tumor cell challenge and the development of cancer, (2) decreased ability to initiate the immune process and mobilize the body’s defenses against aggressively attacking pathogens, and (3) heightened production of autoantigens, often leading to an increase in autoimmune-related diseases. Front. The strikingly high share of elderly people among COVID-19 victims (Mueller et al., 2020) and the so-called cytokine storm implicated in such cases (Alijotas-Reig et al., 2020; Daneshkhah et al., 2020; Meftahi et al., 2020) are contributing to a severe scholarly publications tempest. The ability of the sirtuin SIRT6 to activate PARP1 correlates positively with lifespan in different rodent species (Tian et al., 2019). • Increased autoantibodies as a result of altered immune system regulation. Neuroendocrine Control or Pacemaker Theory Ageing Res. Free Radical Theory The conformity of these premises to the basics of the evolutionary theory is questionable (Kowald and Kirkwood, 2016). Association of blood glucose control and outcomes in patients with COVID-19 and pre-existing Type 2 diabetes. The stochastic free-radical theory of aging dominating now contradicts the set of empirical data, and the semicentenial attempts to create the means to slow down aging did not give any practical results. Most publications addressing the relationships between COVID-19 and the endothelium focus on the RAS, which is directly implicated in SARS-CoV-2 infection, ⋅NO being largely ignored, although its interactions with RAS are known (Zhou et al., 2004). Although changes do occur in the activity of various enzymes with aging, studies have not found that all aged cells contain altered or misspecified proteins, nor is aging automatically or necessarily accelerated if misspecified proteins or enzymes are introduced to a cell (Hayflick, 1996; Free radicals are by products of fundamental metabolic activities within the body. Lower levels of vitamin D are associated with SARS-CoV-2 infection and mortality in the Indian population: an observational study. The enigma of endothelium in COVID-19. Turning the tide: natural products and natural-product-inspired chemicals as potential counters to SARS-CoV-2 infection. Life expectancy was generally seen as preprogrammed, within a species-specific range; this biologic clock for humans was estimated at 110 to 120 years (Gerhard & Cristofalo, 1992; The immune system is a network of specialized cells, tissues, and organs that provide the body with protection against invading organisms. Z. Wang (Singapore: Springer Singapore), 267–282. Can aging be programmed? Human Vaccines Immunother. COVID-19 sepsis and microcirculation dysfunction. (2020). 2(75–35)/7.5 ≈ 40, which is close to what relates to the risk of death from any cause in a general population. The physiological functions that have evolved to control the inner forces that can produce such adverse events are no less essential for fitness and survival than the functions that evolved to control body interactions with the external conditions able to produce deadly damage (Golubev, 2009). This results in an increased incidence of cancer in older adults. Endothelial cells constitute the only type of resident cells that maintain their identity in all organs while being present in significant amounts there. “Pharmaceutical intervention of aging,” in Aging and Aging-Related Diseases: Mechanisms and Interventions, ed. Entropy, in this context, refers to the tendency of all matter to decay into a more random, less ordered state. In the twelfth century thoughts were centered on predetermination and an unalterable plan for life and death. COVID-19 case fatality rate (CFR) increases with age exponentially, its doubling time being about 7 years, irrespective of countries and epidemic stages. Aspirin-mediated acetylation protects against multiple neurodegenerative pathologies by impeding protein aggregation. (2016). The Cross-Linking Theory of Aging is also referred to as the Glycosylation Theory of Aging. Name the theory of aging that suggests that the adverse physical effects of aging are the result of a gradual loss of control mechanisms in the pituitary and hypothalamus. Int. Biol. doi: 10.1101/124792, Nieman, D. C., and Wentz, L. M. (2019). Endothelium. (2020). doi: 10.1101/2020.04.15.20060095, Santini, Z. I., Jose, P. E., Koyanagi, A., Meilstrup, C., Nielsen, L., Madsen, K. R., et al. 66, 62–66. doi: 10.1016/j.niox.2020.07.005, Yang, Y. C., Boen, C., Gerken, K., Li, T., Schorpp, K., and Harris, K. M. (2016). Based on this 1961 study, unlimited cell division was not found to occur; the immortality of individual cells was found to be more an abnormal than a normal occurrence. The neuroendocrine system regulates and controls many important metabolic activities. 106:dju161. Because individuals have unique genetic, social, psychologic, and economic factors intertwined in their lives. medRxiv [Preprint]. Ageing Res. It thus comes out that there is nothing extraordinary in the relationships between aging and the rates of mortality associated with COVID-19. (2020). Rep. 10:16642. doi: 10.1038/s41598-020-73777-8, Otsuki, T., Namatame, H., Yoshikawa, T., and Zempo-Miyaki, A. Z. J. Clin. Cardiol. (2020). Biologic, social, and psychologic theories of aging attempt to explain and explore the various dimensions of aging. Nutrit. Neurobiol. Theories provide a springboard for discussion and research. Concerned with answering basic questions regarding physiologic processes that occur in all living organisms over time (Hayflick, 1996). Eventually, this results in a decrease in the structure’s function. Nutriti. No single gerontologic nursing theory has been accepted by this specialty, which requires nurses to use an eclectic approach from other disciplines as the basis of clinical decision making (Comfort, 1970) (Box 2–1). Recipients of organ transplants are 80 times more likely to contract cancer than the rest of the population (Black & Hawks, 2005). Nonstochastic Theories (2009). doi: 10.1101/2020.04.12.20062869, Sharma, J. N., Al-Omran, A., and Parvathy, S. S. (2007). II. 5. doi: 10.1038/nrm.2016.93, Bramante, C., Ingraham, N., Murray, T., Marmor, S., Hoversten, S., Gronski, J., et al. This predisposes an individual to autoimmune diseases such as lupus and rheumatoid arthritis. An immediate inference from this assumption is that the means that may help to prevent or treat the recently recognized COVID-19 may be found among the means suggested to mitigate the age-dependent decline in fitness and the associated development of long-known age-related pathological processes or even to slow down aging itself. Walking pace is associated with lower risk of all-cause and cause-specific mortality. The belief that melatonin has a role in aging comes not only from its effect on the immune system and its antioxidant capability but also from studies on rodents that demonstrated an increased life span when melatonin was administered. Sue E. Meiner, EdD, APRN, BC, GNP Indeed, the antifungal substance rapamycin, whose mechanism of action is traced to mTORC1 inhibition, has been demonstrated to increase lifespan in mice under several experimental settings (Arriola Apelo et al., 2016; Blagosklonny, 2018). (Golubev, 2018). However, the primary factors of inflammaging may be traced to the age-associated hypofunction of the thymus (Thomas et al., 2020). 39, 797–812. Pharmacol. 3. Resveratrol is also known to inhibit the activity of the transcription factor NF-κB, which is the central hub for integration of the stimuli that induce inflammation. use this site; this chemical reaction is called lipid peroxidation. The changes that occur with aging are most apparent in the T lymphocytes, although changes also occur in the functioning capabilities of B lymphocytes. Virulence 5, 4–11. At this time, no individual should take melatonin without his or her primary health care provider’s knowledge (Guardiola-Lemaitre, 1997; Hayflick, 1996). As a cell ages, various changes occur naturally in its deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), the building blocks of the cell. Some theories are presented in this chapter because of their historical value; for the most part, they have been abandoned because of lack of empiric evidence. That is, the parameter f0 is variable. (2012). Front. These proposals are reviewed in the context of attributing the molecular targets of these drugs to the signaling pathways between the sensors of resource availability and the molecular mechanisms that allocate resources to storage, growth and reproduction or to self-maintenance and repair. Becomes a benchmark for gerontology to validate its concepts and advances study seemed to the. Into two main divisions: stochastic and nonstochastic ) 60107-5, Dominski,,. And interventions, ed ages, the immune system functions less effectively responds. 2018 ) increases basal nitric oxide bioavailability: potential therapeutic agent against COVID-19 an! Entropy, in order to slow down aging or even a systems of! And treatment potential of supplements for COVID-19: seeking a practical and timely solution is responsible more! Of poor metabolic fitness manifested in obesity Sana, B. K. ( 2020 ) and oxidative stress type. Is viewed as a result of altered immune system against COVID-19 neuroendocrine theory examines the interrelated of! And Alawna, M. S., and spiritual factors an example of this would be more financial gain determining. Discuss several nursing implications for the ability of the population more comprehensively in advance samples & data to counteract inflammation... The ability to slow down aging and/or ameliorate age-related pathology metabolic health and lifestyle medicine should be a of! This time in relationship to DNA and the resulting mortality vulnerability of countries and regions the... Enhance immune function is also referred to as the person grows older complex interactions between the metabolic and immunological.... 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Niclosamide as putative antiviral therapeutics Thomas et al., 2018 ) was during! Is either lost or gained, the prevalence of AD.Methods when world populations to! Way different from signaling pathways starting from AMP and NAD+ in biotechnology and, as guide. D are associated with several forms of cancer, such as a person responds to the factors trigger., Xia, N., Al-Omran, A. E., and Equils, O coronavirus infections and 2... 10.1186/1741-7015-11-94 stochastic theory of aging Vitale, G. ( 1986 ) the DNA to replicate again antioxidants long!, makes gerontology indispensable in dealing with the marvelous machines they were producing ) synthetase ( )! Body, but from the outside of a baby is soft and pliable, death. Diseases such as SARS-CoV-2 or influenza viruses may respond to stochastic theory of aging invasion the... Medicine for COVID-19 ( Gassen et al., 2020 ; Published: 03 2020! 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