Anti-Aging Drug Discovery on the Basis of Hallmarks of Aging

Anti-Aging Drug Discovery on the Basis of Hallmarks of Aging is a comprehensive and timely book on all aspects of anti-aging strategies. The book provides comprehensive, foundational knowledge on the mechanisms of aging and current anti-aging strategies and approaches developed. Aging research has experienced an unprecedented advance over recent years with the discovery that the rate of aging is determined, at least to some extent, mainly by our genetics and modulated by environmental factors. The hallmarks of aging describe the molecular and cellular processes that govern biological aging and their variation in individuals.

• Covers different aspects of anti-aging research, from foundational knowledge to future perspectives
• Provides understanding on the different hallmarks of aging and how they can be applied in the development of anti-aging drugs
• Discusses various anti-aging strategies, including telomerase reactivation, clearance of senescent cells, stem cell-based therapy, and others

• Language: English
• Publisher: Academic Press
• Release date: Jul 19, 2022
• ISBN: 9780323902366

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Preface

Sandeep Kumar Singh, Chih-Li Lin and Shailendra Kumar Mishra

Population aging is a global phenomenon, indicating aging is already a major problem in most countries. However, no effective intervention was found to slow, stop, or reverse the aging process in humans. With this background, it was very timely to develop effective drugs for antiaging. However, considering various concepts and theories, there is actually no single mechanism that can perfectly explain the entire aging process. This indicates that various aspects should be considered at the same time in the process of drug development and design. As a result, this book includes chapters contributed by selected invited researchers. It provides a comprehensive thinking on the strategy of developing antiaging drugs in a multifaceted manner based on the currently known theories and evidence. The Antiaging Drug Discovery on the Basis of Hallmarks of Aging focuses on selected topics that are emerging and important new research on the promising strategies for antiaging drug discovery. The main area covered in this book comprises the general focus of most recent advances that may ultimately contribute to slowing or reversing the aging process and covers topics such as reactivation of telomerase, epigenetic approach, chaperone-related proteases controlling, stem cell-based therapies, and key signaling pathways associated with aging. This book summarizes the key points of each chapter according to hallmarks of aging and considers the practical implications for strategies of antiaging drug development. Collectively, we are confident that Antiaging Drug Discovery on the Basis of Hallmarks of Aging will be of great value in supporting the multidisciplinary efforts to understand many functions of the aging process, which will undoubtedly lead to the discovery of new pharmacological targets and therapeutic tools for the prevention and treatment of aging and aging-related disorders. Finally, we express our deepest thanks to the members for their incredible dedication and contributions. The excellence of this book is largely due to their efforts.

Chapter 1

The aging: introduction, theories, principles, and future prospective

Shabnam Shabir and Mahendra P. Singh,    School of Bioengineering and Biosciences, Lovely Professional University, Phagwara, Punjab, India

Abstract

Aging is psychosocially and biologically defined as being older. An aged or geriatric patient is defined as a person whose biological age is advanced. Aging can be characterized as a deterioration of the physiological functions essential for survival and fertility that is time-related. Aging is a complex spatial and temporal hierarchy of dynamic activities that are integrated over the life cycle of a complex dance. Thus aging is not easily dissected into disjoint subprocesses; it is a dynamic, multidimensional, hierarchical process. In most body structures, aging is followed by incremental modifications. Aging biology research focuses on understanding both the cellular and molecular mechanisms that underlie these changes and those that accompany the onset of age-related diseases. As time passes, aging takes place in a cell, an organ, or the whole body. It is a phase of every living thing that goes on through the whole adult life cycle. Aging is an organism’s sequential or incremental transition that results in an increased risk of fatigue, illness, and death. Aging is multifaceted. Therefore, there are various hypotheses each of which may clarify one or more aspects of aging. Aging in humans reflects the accumulation over time of changes in a human being that may involve social, psychological, and physical changes. Recent hypotheses are assigned to the concept of damage, whereby the accumulation of damage (including DNA oxidation) may cause biological systems to fail, or to the concept of programmed aging, whereby problems with internal processes (epigenomic maintenance can cause aging such as DNA methylation) are correlated with the causes of aging.

Keywords

Aging; senescence; aging theories; antiaging therapies; stem cell therapy

1.1 Introduction

Aging is marked by many pathologies, the result of the loss of homeostasis and the accumulation of molecular damage eventually leading to death and biology (Vijg, 2014). The aging of humans involves many changes at various stages. These are more noticeable than others, such as lines or gray hair. Changes in age often arise on a physiological and functional basis. In general, after peak output in the third decade of life, most functions start to decline linearly (Zheng, Yang, & Land, 2011). Although there is significant individual variability and not two individuals alike, aging is steadily decreased, has a lower metabolic rate as well as longer response times and decreased sexual activity as other physiological and functional characteristics (Arking, 2006). Aging is characterized as a process of losing viability and increasing vulnerability as an intrinsic, unavoidable, and irreversible age-related process (Comfort, 1964). Many chronic illnesses have aging as the greatest risk factor. The number of coexisting chronic conditions, generally referred to as multimorbidity, increases with age, as demonstrated by broad population studies (Vetrano et al., 2017)). The fundamental similarity of biological processes in living systems suggests that the aging process is governed by a general mechanism. While there is no consensus on the existence of such a unifying aging mechanism, modifications in informative biomolecules are thought to play a key role in the etiology of age-related degenerative processes. The two radically different schools of aging theories, according to which aging is viewed either as a species-specific genetically defined program or as a sequence of stochastic events, should first be attributed to molecular biological theories of aging (Schneider, Gudladt, & Gerold, 1987).

Changes in body structure, energy output and consumption imbalance, homeostatic dysregulation, neurodegeneration, and neuroplasticity loss are all phenotypes of the aging phase (Toescu & Organelles, 2007). As a result, disease susceptibility increases, functional reserve decreases, healing capacity decreases, stress resistance decreases, and health becomes unstable. Eventually, failure to thrive will occur. Gerontological and geriatric research is primarily focused on preserving physical and cognitive function, but it is important to note that achieving this aim necessitates a thorough understanding of the biochemical, physiological, and cellular processes that ultimately dictate functional changes (Lange & Grossman, 2010). Despite progress in molecular biology and genetics, it is still important to reveal the mysteries that manage human life. There are various explanations to explain the aging process awning two key classes: programmed theories and error or damage theories, but none of them seem fully satisfactory. These hypotheses can be difficult to interpret. The awareness and testing of the current and new aging hypotheses will promote successful aging (Jin, 2010). A few hypotheses may clarify the typical maturing measure, either alone or in blends with different speculations. These speculations are isolated into two classifications: developmental, which manages recorded and transformative parts of maturing, and physiologic, which manages primary and practical movements (Goto, 2008). Cycles fit for clarifying these hypotheses in cell structure incorporate natural planning and signals, unplanned events, hereditary signs that increment an organic entity’s weakness to mishaps, atomic or mitochondrial DNA changes or harms, harmed and strange proteins, cross-linkage, squander develop, general subatomic mileage, and free extreme types of shape. Oxidative pressure, immunology, neuroendocrinology, metabolic and insulin flagging and caloric limitation are physiological systems that may clarify maturing (Marín-García, 2007).

Throughout the most recent decade, the hypothesis of oxidative pressure was unmistakable with expansion contemplates looking at the utilization and impacts of cancer prevention agent nutrients (Gupta, Shridhar, & Dhillon, 2015). Free extreme advancement of radical ongoing oxidation and diminished body openness to natural poisons has been hypothesized to be forestalled by exorbitant openings to daylight, such as skin malignant growth, by ingestion, including stomach or intestinal carcinoma; macular degeneration and waterfall; prostate malignancy and Alzheimer’s sickness; and inward breathing including cellular breakdown in the lungs and constant lung infection, which could hinder the cycle of ordinary maturing. The theory is that the aggregation of proteins, DNA damage and lipids because of hypothermia and digestion is the result of profoundly responsive oxygen-determined substances such as free radicals (Willcox, Ash, & Catignani, 2004). It is believed that reactive oxygen can be a signal for aging and that the aging process and the lifetime of its tissue levels can be determined. However, most of the studies, if not all of them involving antioxidant-vitamins, have not been effective. The oxidative stress hypothesis is partly linked to another theory of natural aging, which is related to chromosomal changes (Tudek et al., 2010). Research showing that mitochondrial DNA mutations in the gene in the oxidative stress pathway may help reduce resistance to oxidative stress supports this theory (Gardner, Sutherland, & Shaffer, 2011). Nevertheless, such research has a very limited effect on nondiseased aging. The autoimmune theory, that the human body is essentially beginning to produce autoanticorps to its very own tissues or to produce time-acquired deficits mainly in T-cell function, is another common aging theory. It predisposes older people to infections, chronic diseases and cancer, especially autoimmune diseases such as rheumatoid disease (Jin, Simpkins, Ji, Leis, & Stambler, 2015) (Fig. 1.1).

Figure 1.1 The characteristics of the aging mechanism suggested in part by age-related shifts.

The theory of neuroendocrinology suggests that an increase in cortisol or chronic pressure over the years will lead to natural aging later on in elderly individuals. Examples may be slower infection reactions, age-related loss of memory, decreased muscle capacity, and chronic inflammatory conditions. It is expected that the typical maturing cycle might be diminished by a multimodal idea of the guideline of constant fiery infection on a neuroendocrine-resistant premise. However, there has been no positive evidence in scientific studies (Yiallouris et al., 2019). Studies that suggest that longevity appears inheritable in humans in connection with the existence of particular genes support this hypothesis (Cefalu, 2011). Important evidence shows, however, that physical exercise also increases human lifespan, and the principle of calory restriction contradicts this. This recently became a common explanation for normal aging in human beings, as extensive research has shown that caloric limitation is correlated with cancer, cardiovascular disease, Alzheimer’s disease (AD), and sarcopenia (Campisi et al., 2019). The stabilization of cell membranes is one process that is hypothesized, avoiding the functional decrease of aging. Research in people, however, is not enough. However, there is a shortage of studies in humans. Loss of equilibrium between different physiologies and their ability to adapt to the environment, sometimes known as homeostasis as a result of human aging, requires modifications to the physiology that normally contribute to a decline in functional age (Beckman & Ames, 1998). Aging can therefore be characterized in conjunction with an increase in vulnerability and mortality by age as progressive deterioration of physiological function. A mechanism that integrates improvement in different aging components and is the key center of the biogerontology research can be considered an elementary procedure of aging or senescence (Reisberg et al., 1999).

1.2 Modern theories of aging in biology

There are several suggestions to describe the aging process, but none seems to be entirely satisfactory (Davidovic et al., 2010). The conventional theories of aging say that aging is not genetically programmed or adapted. Modern human biological aging ideas come into two major categories: theoretical of programming and damage or error. The theories programmed suggest that aging is in line with a biological agenda, perhaps a continuation of one that governs the development and growth of children. This control will rely on modifications in the expression of the genes that affect the maintenance, repair, and defense. The theories of damage or error highlight environmental attacks on living organisms, which cause aging at various levels of cumulative damage (Kochman, 2015).

1.2.1 Three subcategories exist in programmed theory

1.2.1.1 Programmed longevity

Aging results from the sequential on- and off-line switching of certain genes and is characterized as the period when aging-related deficits are present (Davidovic et al., 2010).

1.2.1.2 Endocrine theory

To regulate the aging rate, biological clocks operate by hormones. Recent studies have confirmed that aging is regulated hormonally and that the evolutionary mechanism of IGF-1 signaling (IIS) plays a central role in the hormonal regulation of aging (Akintola & van Heemst, 2015).

1.2.1.3 Immunological theory

The mechanism would gradually debilitate, leading to an increased risk of contagious diseases, aging, and death. The effectiveness of the immune system increases in adolescents and subsequently worsens slowly with age. For instance, as anticorps grow older, they lose their efficacy, and fewer new conditions that cause cellular stress and eventual death are effectively combated by the body. Indeed, inflammation, cancer, cardiovascular disease, and AD have included a dysregulated immune response (Cornelius, 1972). Although there were no clear causal links to any of these negative results, there was at least indirect involvement of the immune system (Rozemuller, van Gool, & Eikelenboom, 2005).

1.2.2 The error or damage theory has the following subcategories

1.2.2.1 Wear and tear theory

There are essential elements of cells and tissues that wear out and result in aging. Oxidative stress, toxins, physical and chemical contaminants results in gradual deterioration of the cells/tissues of the body via wear and tear. Thus in 1882, the idea of wear and tear of aging was first presented to many people by August Weismann, a German biologist, as the most common items around them still sound perfectly reasonable (Hulbert, Pamplona, Buffenstein, & Buttemer, 2007).

1.2.2.2 Rate of living theory

The higher the rate of basal oxygen metabolism of an organism, the shorter its service life. The theory of aging, although helpful, does not justify the overall lifespan entirely (Brys, Vanfleteren, & Braeckman, 2007) (Fig. 1.2).

Figure 1.2 Specific oxidative damage mechanism for biomolecules in aging.

1.2.2.3 Cross-linking theory

Johan Bjorksten suggested the cross-linking hypothesis of aging in 1942. The accumulation of interconnected proteins destroys cells and tissues according to this theory, which slows body processes resulting in aging (Bjorksten, 1968). Recent studies have shown that the age-related modifications of the proteins being examined involve cross-linking reactions (Harman, 1992).

1.2.2.4 Free radical theory

Superoxide and other free radicles are responsible for destroying the cell macromolecular components and causing aggregated cell damage and subsequent organ failure. Sugars, nucleic acid proteins, and lipids may be openly attacked by macromolecules. Nucleic acids can have an additional base, a double-stranded fragmentation in the backbone and a cross-link to other molecules. Reactive oxygen species (ROS) signaling perhaps the most critical enzyme/gene mechanism for cell senescence and organism aging and the further advancement of a free radical theory of aging may be considered through ROS signaling (Afanas’ev, 2010).

1.2.2.5 Somatic DNA damage theory

In cells of living organisms, DNA damage is constant. While these damages have ultimately been fixed, they cannot be as quickly revised as the polymerase DNA and other repair mechanisms. In particular, DNA damage buildup in nondividing mammalian cells is seen. Genetic mutation occurs, builds up and deteriorates cells with growing age. Damage to mitochondrial DNA in particular may lead to mitochondrial dysfunction. Damage to the genetic integrity of the cells of the body causes aging (Campisi, 2000).

Overall, although many aging theories have been suggested, there is currently no consensus on this subject. Many of the hypotheses proposed interact in a dynamic way with one another. It is possible to help good aging and to improve human life by understanding and testing current and new aging theories (Herbig, Ferreira, Condel, Carey, & Sedivy, 2006).

1.3 Principles

The aging population, from skill and age, revenue and culture to sexuality, is extremely diverse. Active aging has been the backbone of seven dimensions of wellness-spiritual, physical, intellectual, social, cognitive, environmental, vocational, and wellness. They are also essential for the delivery of a variety of services and environments that meet the needs, desires, and aspirations of more than 50-plus people. In many species, caloric restriction has a significant impact on lifespan, including the potential to postpone or avoid a number of age-related diseases (Guarente & Picard, 2005). This usually includes 60%–70% intake from calories while retaining the correct intake of nutrients that an ad libitum animal consumes. This has shown a lifespan improvement of up to 50% in rodents; similar results are observed in yeast and Drosophila (Agarwal & Baur, 2011).

Alterations can also show the advantages of dietary restrictions by modifying the macronutrient profile to minimize the consumption of protein without altering the calorie level, resulting in similar longevity increases (Nakagawa, Lagisz, Hector, & Spencer, 2012) (Fig. 1.3).

Figure 1.3 An inclusive physiological view of the changes observed during aging.

Dietary protein restriction inhibits not only mTOR activity but also IGF-1, two aging mechanisms. In particular, leucin intake reduction is necessary to inhibit mTOR activity, which can be achieved by decreasing the consumption of food in animals (Fontana, Partridge, & Longo, 2010). Sleep quantity influences the death rate. People who live the longest report sleep 6–7 hours a night (Patel et al., 2004).

Exogenous and endogenous factors in aging can be found that support the theory that it does not cause an individual aging factor but contributes to it with multiple associated mechanisms and that the equilibrium between them determines the progression of aging in the individual (Ames & Gold, 1991). A steady shift in life habits is accelerating aging, so consistency in biological cycles of young people, in particular the sleep–wake cycle, is needed to achieve healthier aging to stay stable (Antoniadis, Ko, Ralph, & McDonald, 2000). The aging mechanism is not well known and is far from possibly being reversed or extended. The formula of eternal youth has not yet been found (Fernández-Ballesteros, 1999).

In all organ systems, physiological changes occur with aging. Decreases the heart output and raises blood pressure, frequently contributing to arteriosclerosis (Boss & Seegmiller, 1981). Thus several studies have focused on physiological modifications with age, and some of the leading studies are briefly referred to, while all these modifications are listed in Table 1.1.

Table 1.1

According to genetic factors, the natural lifespan of each species, which is 120 years in humans, is determined by longevity. The main goal is to ensure that life expectancy is equalized with this optimal fixed lifespan, meaning the secret of prolonging life is the art of learning not to shorten it (Turner, 2003). The aging systems evolve over the following sequences in human developments: shorter telomeres, aging mitochondria, accumulation of mutations, genetic aging expression, apoptosis atrophy of the somatic, and apoptosis atrophysical composition of female reproductive materials (Bowles, 1998).

1.4 Extrinsic and intrinsic factors on aging

Technology has consistently led to biomedical studies and many breakthroughs in aging biology, and technological developments have been possible, including the genetic studies described above. The sequences of genomes in particular opened up at the beginning of the 21st century a new period of biological science leading to remarkable advances in the biology and genetics of the elderly (Anderton, 2002). Genetic longevity research can now be conducted at the entire genome level, evaluating all genes of the genome for long-term association rather than concentrating on only a few candidates at the same time, and genetic screens in large-scale model organisms can be performed to discover new genes that control aging (Bowles, 1998).

While aging and death are unavoidable, many elderly people remain cognitive and physically active, despite the decrease in aging function. This segment examines lifestyle choices that appear to be linked to increased longevity and improved living conditions in older people (Drozdowski & Thomson, 2006).

1.4.1 Circles and systems of social support on aging

Several studies have indicated a decreased risk of cognitive and physical decrease in maintaining a wide web of personal links with and daily involvement in productive and social activities. Similarly, social decay is a high-risk factor for cognitive and physical decay, characterized as having little to no social relations (Sowell et al., 2003).

1.4.2 Smoking on aging

Smoking reduces the lives of people by an average of 14 years. Many deaths are due to smoking rather than HIV, illicit use of narcotics, alcohol consumption, car crashes, suicides, and killings. Each year, smoking causes one in five deaths from the following ailments in the United States:

• Cancer: Smokes can contribute to lung, larynx, esophagus, liver, pancreas, blood cell, and cervix cancer.

• Respiratory problem: Infections that can interfere with breathing are more common in smokers than in nonsmokers, such as flu and pneumonia.

• Lung disease: Smoking damages the air passage and lungs, causing chronic bronchitis and emphysema from time to time.

• Osteoporosis: Smokers are more likely than nonsmokers to develop osteoporosis.

• Heart disease: Smoking may increase the risk of stroke and heart attack (Centers for Disease Control and Prevention CDC, 2012).

1.4.3 Leisure activities on aging

Many studies indicate a steady reduction in cognitive impairment in leisure activities, particularly in relation to Alzheimer’s and extreme vascular disease dementia. To a certain degree, the decrease in risk is linked to the level and form of involvement of leisure activities. Recreational activity can be split into two subgroups: physical and cognitive (Morley, 2004).

1.4.4 Diet on aging

Diet is an important part of the prevention and management of weakening physical and cognitive conditions, particularly for elderly people. Too much or too little nutrient can have adverse effects (Woo, 2000). Individuals do not consume the necessary amount of protein and nutrients in undernutrition, which is different from the calorie restriction listed in the section on Theories of Aging for optimal health (López-Otín, Blasco, Partridge, Serrano, & Kroemer, 2013).

1.4.5 Physical health effects of exercise on aging

The physical health of elders is beneficially affected by exercise. Higher levels of physical activity have been linked. Increased survival, delayed disability development, delayed functional loss, improved balance and strength, minimized falls and fractures, higher quality of life, and mood enhancement. Exercise services are an integral part of the management of people who have chronic diseases or recover from acute diseases. Education for training should be customized to an individual’s age, gender and prescription goals and capabilities (Rughwani, 2011).

However, older adults should be given 30–60 minutes of moderate intensity per day (5–6 on the scale of 0–10) or 75–100 minutes of intense exercise per day (7–8 on the scale of pain 3–5 days per week). The elderly should either have a weight lifting and calisthenics of moderate to intense intensity 2 days a week and a stability training of 2 days a week. For each operation, stretching is also advisable (Daniels, Arena, Lavie, Cahalin, & Forman, 2013).

1.4.6 Cognitive health effects of exercise on aging

In a new longitudinal study of 15 studies involving over 33,000 individuals followed for up to 12 years, the protective effects of daily exercises on cognitive health were reported. The study showed that the security of all levels of physical activity against cognitive deterioration is substantial and consistent. A drop of 35% was associated with a reduction in the risk of cognitive failure. However, people with the highest regular exercise were much less likely to develop cognitive disability symptoms over time than individuals with very low levels of activity (Vincent, Raiser, & Vincent, 2012).

1.4.7 Aging intervention and future stem cell research

Aging has been followed by a decrease in both tissues’ and organs’ cellular regenerativeness. The age-related decline in stem cell function may be due to a decrease in the renewal activity of these tissues. Researchers are focusing on discovering new methods to treat age-related disorders and certainly cure them one day in the area of stem cell therapy (Piccin & Morshead, 2010).

1.5 Future perspective (aging therapies)

Aging is a phenomenon characterized by many pathologies, in which the loss of homeostasis and the accumulation of molecular damage eventually contribute to death and biology (Vijg & De Grey, 2014). However, if disease is characterized as structural or functional disorder or abnormality, aging is definitely not an illness, as everyone suffers from it, while aging and disease also overlap (Cheng & Gunderman, 2020). However, the study was very early, and there is still a long path toward longevity. In addition, it is unlikely that a magic bullet will be present to the aging due to the multifactorial nature of the aging process (Sethe & De Magalhães, 2013).

1.5.1 Caloric restriction

Some have claimed this to be the result of increased free radical formation within the mitochondria, which causes an increase in the protection capacities of antioxidant secondary induction, while others suggest that the lack of nutrient access causes metabolism to be optimized (Shimokawa & Trindade, 2010). Others suggest that the genetic program could have slowed down indirectly, affecting aging, in view of observations made in mice. In addition, as CR also causes numerous changes, both at the hormone and proteome stages, it is recognized that caloric restrictions may be the sole therapy that can delay aging (Baumeier et al., 2015).

1.5.2 Stem cell therapies

The general population has been continually and extensively inflamed with stem cells and is well deserved. Then, it is no surprise that stem cells were marketed as possible therapies for aging and rejuvenation diseases (Peng, Xuan, Leung, & Cheng, 2015). While the loss of stem cells in aging is thought to have a part in aging, the decline in the functions of the stem cells is largely unknown, whereas the durability of aging factors is still vague, and the mechanisms are accurately understood (Karimi, Raoufi, & Bagher, 2020). Applications for stem cells are very early, and more research is needed, especially at the tissue-specific level, where variations in the mechanisms and signaling pathways may lead to substantial exceptions when aging is delayed (Robinton & Daley, 2012).

1.5.3 Hormonal therapies

In moderation, comprehension of early-age evidence for sufferers with GH and IGF-1 deficiency, the growth hormones are antiaging treatment and evidence shows that the benefits to human GH in older and hgH addition in libido growth, muscle mass growth, and improvement of immune system (Taub, Murphy, & Longo, 2010). New research is essential for the assessment of any possible negative effects and for the effective use of therapeutic agents (Liu et al., 2007).

1.5.4 Telomere-based therapies

When expansion of telomeres in vitro increases the cell’s capacity to proliferate and accounts for the reversal of tissue degeneration in mice, the rates of aging can be reduced. That is definitely the central idea behind the marketing of telomere measuring kits by some firms, intended to estimate people’s biological life and to some degree the risk of developing telomere-related shortness of life, such as coronary heart disease, hepatic cirrhosis, and atherosclerosis (Samani, Boultby, Butler, Thompson, & Goodall, 2001). In addition to the promotion of tumor growth and cell proliferation, there is a well-founded concern that the use of such activators might increase the risk of developing cancer. The expression of telomerase has long also been related (Peterson, Mok, & Au, 2015).

1.5.5 Therapies to come

There are several approaches to slowing aging that have yielded encouraging initial results. One such strategy is the use of rapamycin. This is a widely used vaccine for preventing the rejection of organs. Rapamycin has been shown to prolong the maximum lifespan of mammalian organisms, but whether the medicine delays mammalian aging or whether it has isolated effects on the survival of mammalian cancers, which are the major cause of death in mouse strains, remains to be determined (Horvath, Lu, Cohen, & Raj, 2019). Aging appears to be a consequence of the klotho gene, which encodes one membrane protein and a secreted hormone transcript, as mutations in this gene can cause rapid and low expression during mouse aging. Klotho overexpression, in fact, prolongs life by approximately 30% (Kurosu et al., 2005).

Perhaps the more futuristic antiaging treatment, in our collective imagination at least, is nanotechnology that might, in part, be attributed to the book in which the word was invented, Creative engines, which instantly evokes visions of tiny, extremely complex nanomachines or nanobots often also called nanites. In a wide variety of applications, nanotechnology has many promises and aspirations (Agostini et al., 2012). Thus there is a hope that nanostructures such as these will lead to the slowing down or even reversing of chemical reactions and harm that occur with aging by reversing the chemical reactions.

1.6 Summary

After researching various concepts and aging theories, none of these explains the entire process, as aging is known as a multifactorial process. Aging is related to the progressive cell degeneration and regenerative capability failure of two common processes. Both procedures occur in any phase of life and, under normal circumstances, remain perfectly balanced. However, the equilibrium becomes lost when aging, and it begins to degenerate. The deteriorating mechanisms mainly relate to the generation of ROS and protein glycosylation; both processes are closely related to environmental factors. On the other hand, genetically modified shorter telomeres and cell death processes determine the loss of proliferation and regeneration ability. Aging is one of the most complex biological mechanisms called senescence. Theories of aging are usually known as theories of program or damages. More recently, combined hypotheses have arisen that consider the aging process to be more systematic and global, but the final details remain unclear. The complexity of the aging process has meant a greater understanding of the aging processes through an integrative strategy. Omics may play a critical role. In particular, omics-genomics, proteomics, metabolomics, lipidomics, and transcriptomics may be key to illustrating and functionally interconnected changes at different levels of the molecular hierarchy during aging; moreover, recent information on these molecular interactors is still very restricted. There has been a rise in proof over recent decades that the aging process is not an unavoidable one. There are also a variety of mechanisms available now that significantly extend the life cycle.

Maximum reported mechanisms have been analyzed for extending life in simpler organisms and still need to be illustrated as a fully functioning human antiaging hypothesis. This truly does not restrict cognitive impairment characteristics and aging. Biogerontologists should bear in mind this connectivity, which frequently obscures the major sources of aging and considerably decreases the ability to clear and conclusive findings, whereas aging research flourishes. Enhanced prevention, early detection and rationally structured treatment methods have historically been hindered by inadequate attempts to generalize study results in younger populations to elderly people. Current research in geriatric psychiatry remedies in order to explain the dynamic interaction between aging and pathophysiological mechanisms underlying psychiatric disorders.

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