Individuals who maintain robust and regulated immune systems are likely to have longer lifespans with reduced incidence of age-related infections. However, a majority of the elderly population are subject to compromised immune systems due to a set of challenges occurring to their bodies both at the cellular and at the environmental levels. The bulk of these negative changes are referred to as immunosenescence. In more elaborate terms, immunosenescence references the set of complex cellular changes that take place in every component of the immune system, as well as the local external environment, that culminate in reduced immune responses as individuals grow older. It is a two-sided condition characterized by; one, highly ineffective immune response and protection from infections or lifestyle conditions such as cancer and diabetes and; two, high levels of age-related inflammatory challenges. Demographic predictions for the United States suggest that about a quarter of the entire American population will be aged 65 years and beyond by the year 2040. And, considering the advances in healthcare such as the launch of Medicaid and the Healthy People 2020 programs, a majority of this population is anticipated to live to at least 80 years. Yet, despite these advances in health care, a majority of the older adults in the United States continue to endure ill health for at least the last ten years of their lives. Thus, the objective of this research is not to identify an extension to life; rather, it is intended to identify potential measures for extending healthy lifespan in the older population.
About Immunosenescence
Translational studies have revealed that increases in lifespan do not necessarily coincide with better health-span; that is, the period of life spent under minimal interruption by serious chronic diseases and disability ( Berrut & de Decker, 2015). In reality, the longer an individual lives beyond the ages of 65, the higher their chances of contending with physiological dysfunctions in various tissues, organs, and organ systems- immune system included. The dysfunction of the immune system triggers a progressive reduction of the body’s appropriate cellular responses to vaccinations and infections. This occurrence, called immunosenescence, is multifactorial and impacts natural immunity and acquired immunity alike ( Berrut & de Decker, 2015) . It is widely recognized by science that immunosenescence's effect is most profound in the T-lymphocytes. This makes the aging process to be more dramatic for cases of acquired immunity than it is for innate immunity. Overall, several factors contribute to immunosenescence, including previous exposure to pathogens, biological sex, human cytomegalovirus (HCMV) status, physical activity, nutrition, and genetics ( Gems, 2011). With regard to sex, men and women are affected differently by immunosenescence. Women are more likely to develop immunosenescence later in life than men. The phenomenon is attributed to the fact that androgens are immune suppressive while estrogens enhance the immune response. It explains why women generally have a longer life span as compared to men; one which can be taken as a cue for developing gender-specific therapeutic interventions for immunosenescence. Sufficient understanding of the patterns of immunosenescence and the age-related disorders under immune regulation is vital for the identification of the intervention strategies. These strategies could include effective induction of vaccinations to mediate the immune rejuvenation process.
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Aging is a flexible process that can be defined by both nutritional and pharmacological choices. It, therefore, means that the immune system is secretly flexible and can be restored in the aftermath of immunosenescence. Yet, not all the processes for rejuvenating the immune system are validated by research and could turn out to be counterproductive and highly disastrous. Specifically, there could be different factors in a person's youth that could be responsible for the adaptation or response to immunosenescence. The different stimuli that an individual undergoes during early life should be used to develop personized immunosenescence intervention to realize safer rejuvenation of the immune system. In the wake of this realization, bioethicists and policy-makers who explore the ethics of ‘anti-aging’ medical interventions consider the current research as a chase of immortality, which should be given a thoughtful analysis before being endorsed. Concerns are on the potential of the anti-aging treatments to bring dramatic consequences on human aging (McElhaney & Effros, 2009). As a consequence, i mmunosenescence remains a subject of controversy, holding both the promise of a better and longer life while also rousing uneasiness about the social and health consequences that come with the search for post-human immortality. Due to the conflicting perceptions on the efficacy of the interventions to i mmunosenescence, the current research singles out on the most relevant strategies that are under investigation in the search for healthy aging.
Incidence of I mmunosenescence
The primary indicator of a loss in immune functionality due to age is the increase in the occurrence and severity of certain infections. The severity of the infections is usually raised by 20% when a person is aged 60 years and more ( Crooke et al., 2019) . Some of the infections whose prevalence rises following the decline in immune strength include West Nile virus, varicella-zoster virus, pneumonia, tetanus, and influenza. The occurrence of these conditions can be mitigated by repeated vaccinations. Repeated vaccination throughout an individual’s life correlates with higher mediated immunity and /or higher antibody responses to the vaccinated infections during old age. Nonetheless, there are clinical researches suggesting that repeated vaccination is not always a permanent or a straightforward solution ( Crooke et al., 2019) . In fact, the responses to vaccines also decrease with increasing age, with the maximal effectiveness of vaccines for those aged 70 years and stretching to just 30%. Thus, while vaccination demonstrates considerable effectiveness in alleviating the burden of infections among the elderly, vaccination programs alone cannot be relied on entirely for the total eradication of infections.
The patterns in vaccination can, however, be relied upon for research into improving immune systems for the elderly. Empirical research and system or hypothesis analysis of vaccinology may advance the current understanding of rejuvenating the immune system ( Crooke et al., 2019) . One area that could be exploited in this manner is the investigation of the peripheral blood responses the following vaccination to identify immune signatures or pathways that relate to immune responses. This system analysis can expand to the recently established field of immunomics to characterize age-associated alterations to the functioning of the immune system.
Evidence from Contemporary Research
The current knowledge and molecular understanding of the intrinsic defects of immunosenescence to human cells can be combined with the hypothesis-driven approaches to vaccinology and immunomics to appropriately model the kind of alterations at the cellular level that can cause healthier aging. Evidence shows that the gradual reduction in tissue homeostasis and physiological functioning of the body are some of the changes that accompany aging (Giefing-Krol et al. 2015). The age triggered changes lowers both the adaptive and innate immunity of the body rendering it highly vulnerable to diseases that ultimately cause death. The immune system protects the body against pathological attacks from fungi, bacteria, and viruses. Additionally, the system is mandated to remove allergenic or toxic substances and elimination of senescent cells. Immunosenescence compromises these functions of the immune system, thereby exposing the body to attack from various diseases. The body's physiological functions directly related to the immune system also get compromised (Costantini, D'Angelo & Reale, 2018). These include the production of the immune cells that are used by the body to monitor and mount a defense against an impending pathogenic attack that stall as a result of the alteration of the system. Aging-associated changes, therefore, cause pathophysiological concerns on the immunity of the elderly. The immune cells mount the first line of protection against the disease-causing pathogens hence hindering their entry and consequent distribution in the body (Giefing-Krol et al. 2015). During acute inflammation or damage of the body tissues, the first line of immune cells that are called to action is the neutrophils. Neutrophils produce antimicrobial peptides, degenerative enzymes, and reactive oxygen species, all of which counter the microbial activities. Aging and hence leads to the production of immature neutrophils and the overproduction of reactive oxygen species (Costantini, D'Angelo, & Reale, 2018). The alteration of the neutrophil functionality leads to a compromised response system to inflammation in tissues and microbial invasion. Monocytes are another group of immune cells that serve as starters of the response to inflammation. The cells differentiate into dendritic cells and macrophages (antigen-presenting cells). Macrophages that mount inflammatory responses depict two phenotypes: M1, the classical phenotype, and M2 phenotype, depending on the prevailing microenvironment (Giefing-Krol et al. 2015). In healthy people, M1 and M2 are at balance but become imbalanced under chronic inflammation. Aging also causes the imbalance of M1 and M2, leading to age-related disease occurrence.
Dendritic cells connect innate and adaptive immunity. The cells comprise of myeloid and plasmacytoid dendritic cells that are antigen-presenting cells that use pattern recognition receptors to detect pathogens (Fulop et al. 2018). Additionally, dendritic cells also contain TLR, RLRs, and ALRS. The expression of the TLRs in the aged changes at both intracellular and extracellular levels. The general alteration in the expression of the dendritic cell impacts negatively on the immune response on the aged against bacterial and viral invasion. Adaptive immunity comprises B cells and the T cells (Costantini, D'Angelo, & Reale, 2018). Immunosenescence causes changes starting from the hematopoietic generation, which results in lowered antibody specificity and reduction in cell diversity. Aging alters the affinity, antibody specificity, and isotype, a phenomenon that explains the heightened vulnerability of the elderly to infections.
Another type of regulatory cell of the adaptive immunity apart from the B cells is the T cells. Its subsets are CD4+, CD8+, and natural killer cells. All these T cells are produced in the thymus gland, whose integrity reduces with the advancement in the age of an individual. As a result, the expression of CD28, CD27, CD40L (co-stimulatory molecules) is diminished (Fulop et al. 2018). These molecules are responsible for the stimulation of the proliferation of naïve T lymphocytes to activity during the pathogenic attack, and the loss of their expression, therefore, is detrimental to the immune system's response towards the pathogen. The loss of their expression is often followed by a lowered immunity to vaccination in the elderly as a result of alterations in the second messenger signal pathways. This knowledge of intrinsic cell defects should successfully inform the design and nature of alterations that can be made at the adaptive cellular compartments to enhance the resistance of the T-cells to senescence. These could include increasing clonality, reducing lymphocyte repertoire, and enhancing autoreactivity. The intrinsic cells defects primarily alter the activation threshold for T cells, induces cellular senescence, and causes differentiation into memory cells. The above analysis leads to four hallmarks of immunosenescence, which require intervention approaches: (a) excessive accumulation of T-cells, (b) inflamm-aging, or lingering levels of low-grade inflammations, (c) low response ability to new antigens. Reversing these patters could be the solution to the challenge of improving the maximal effectiveness of vaccination at old age.
Interventions
With the biological basis for aging already clear, scientists have myriad prospects of altering the aging process. Currently, there are two classes of intervention activities that target the hallmarks of immunosenescence to cause a turnaround in aging. These interventions are, however, still in the stage of clinical trials. One intervention approach targets nutrient signaling and activates them to initiate endogenous repair of the pathways ( Aiello et al., 2019) . The second intervention approach targets the deleterious effects of aging, including senescent cells and dysfunctional stem cells ( Aiello et al., 2019) . These two approaches are currently being examined through clinical trials to establish their efficacy in alleviating physical frailty. In the second approach, the removal of senescent cells is considered effective because it leads to reduced damage to inflation. There are several drugs in the laboratory that facilitate the process of removal of these senescent cells. When it comes to the rejuvenation of stem cells, the clinical trials are conducted in two ways. One is the direct infusion of healthy, uncompromised stem cells, and the other is rejuvenation by the use of factors obtained from young blood. Technology also has a significant role to play in the maintenance of immune function during the last few decades of life. The advent of technology has stirred speculations that genome editing could be applied in the future treatment for aging ( Aiello et al., 2019)
Scope of Treatment
The scope of treatment of immunosenescence can best be identified after responding to the question of whether aging is a disease or not. If a condition is considered a disease, then it should be cured. However, there is an element of evolution in aging, placing the whole immunosenescence intervention in a dilemma. Even from the perspective of modern biogerontology, it is still difficult to classify aging as a separate process from the individual biological processes at the cellular level, which can be classified as pathological, and which contribute to the endpoint of aging. If the solution to the paradox points to aging as being pathological, then its treatment should aim at three different goals.
The first goal of treatment of aging complications is compressed morbidity. Compressed morbidity aims at identifying treatments that offer protection against diseases of the latter stages of life without interfering with the biological pace of the aging process ( Aiello et al., 2019) . Failure to tamper with the underlying aging process requires that the elderly people at the age of 80 looks 80 years old, think like an 80-year-old, but is not troubled by an underlying illness. It is not the case of trying to make an 80-year-old look, think, and act 50 years. It would, therefore, ensure the quality of life of the elderly without necessarily having to extend their lifespan. If this feat can be realized, it would benefit the elderly by improved healthcare at relatively lower expenses. However, this goal is unrealistic because the intervention assumes that disease in old age and the aging process are two separable constructs, which is not the case. The reality is that the aging process increases susceptibility to infections, which in turn facilitate the aging process. This is to say that late-life illnesses and the aging process are part and parcel to a higher degree ( Aiello et al., 2019) . It is nearly impossible to alleviate late-life illnesses without causing an extension to lifespan ( Vaiserman, Koliada & Lushchak, 2018) . However, this goal could be realized partly by encouraging lifestyles that would reduce the chances of late-life illnesses. Healthy eating habits and regular physical activities are considered in this category ( Duggal et al., 2019) .
The second goal of immunosenescence treatment is to arrest aging. Arrested aging is the intention to stop the aging process in its entirety ( Aiello et al., 2019) . It is a quest for immortality unless death occurs as a result of accidents or suicide. The approach would even seek to reverse the aging process. Considering the current level of performances in biogerontology, the goal of arrested aging remains distant and with a highly remote possibility that may take decades or even centuries to be realized.
The last goal is decelerated aging. There is plenty of research to support the possibility of slowed aging, especially when the intention of the experts is to deal with the onset of late-life diseases ( Aiello et al., 2019) . This promise bears important implications and remains the most immediate goal of immunosenescence treatment. Slowing down the aging process through pharmacological means is a highly effective strategy for alleviating the levels of late-life infections ( Shetty et al., 2018) . Decelerated aging may not completely alleviate the risk of falling ill among the elderly, but it will reduce the incidence of these diseases. Reducing the risk of getting cancer at age 50 gives more promise, even with the realization that cancer may still be contacted at the age of 81 ( Pawelec, 2018) . All humanity is bound to die, and there cannot be a promise for zero pathologies. In fact, the reduction of one mortality crisis may end up exposing the patient to other challenges. Successful control of certain conditions has been proved to open the way for the surfacing of newer conditions.
Ethical and Cultural perspectives
Cultural and ethical perspectives are crucial when it comes to the treatment of immunosenescence. Several ethical standards and barriers exist that make it difficult to treat the condition. The ethics of treatment defines the appropriate means of helping the elderly deal with immunosenescence without violating the ethnic and cultural affiliations ( Isidori et al., 2018). There are several ethical rules implemented on how the medical community can address immunosenescence and its treatment. There are ethical theories of aging and healthcare, including an appropriate treatment model for immunosenescence among the elderly population. The theories describe how medical practitioners can interact with the elderly while offering treatment for immunosenescence. The theory of utilitarianism applies to this issue of aging and immunosenescence as it relates to doing more significant good for the elderly in society and helping them achieve health and wellness. The elderly need help to get the right diet and exercise that would improve their immune system and prevent the development of Immunosenescence ( McElhaney & Effros, 2009) . The utilitarianism theory also requires that public health take the initiative and help elderly patients achieve wellness.
Some members of the medical community do not understand the medical significance of immunosenescence and its impact on the health of the elderly. There is also the ethical question of whether physicians can diagnose and treat patients without the involvement of their family members ( Isidori et al., 2018) . The moral values of a neighborhood can prove an obstacle for the medical community to address the issue of immunosenescence in the aging population. Some societies do not consider Immunosenescence as a problem, and will not help the medical community to resolve the issue among the aging population. At the same time, some community nurses may not seem to understand the ethical and legal responsibilities of helping the aging population achieve health and wellness.
Cultural norms and beliefs are reliable indicators of how certain people treat and respond to societal issues. Different cultures around the world have varying degrees of opinions regarding taking care of the elderly. The views of aging differ across cultures and religions and translate to their views regarding diseases such as immunosenescence ( McElhaney & Effros, 2009) . The way a culture perceives old age influences how its societal members interact with and help individuals with immunosenescence.
Different cultures around the world have different attitudes and practices around aging and health. With these cultural perspectives affecting how they address the issue of immunosenescence ( Pawelec, 2018) . In some cultures, the elderly are often removed from the community and relegated to hospitals and nursing homes. Other cultures have put in place measures and initiatives such as training children on the need to respect the elderly and help them achieve health and wellness. The differences in the way communities and cultures treat old age and diseases determine how they address the issue of immunosenescence among the elderly. Some cultures prefer sending the elderly to nursing homes as opposed to helping them, which reduces their influence in helping their relatives recover ( Pawelec, 2018) .
The nursing profession has an obligation and responsibility of creating awareness on the health of elderly patients through health promotion. As the older adult population increases, the health care sector is required to improve their knowledge of immunosenescence and provide intervention for the aging population ( McElhaney & Effros, 2009) . Medical officers are at the center of treating immunosenescence and lower its rate of occurrence among the elderly. This can be done by encouraging interaction among different disciplines in the community, the media, and learning institutions. The public is not sure of their roles in helping deal with this condition, and the appropriate people to help them understand are public health professionals.
The medical profession has the knowledge to address the issue ethically since they understand how to interact with the elderly. They can provide interventions and improve the immunity of the elderly while broadening the scope of cultural patterns to address the health problem ( Fulop et al., 2009) . A multidisciplinary approach is needed to help the public and health officials identify the most suitable intervention measure that can work to improve the elderly.
A cultural perspective of immunosenescence influences its treatment and determines how society relates to the elderly. Many cultures view the elderly with respect and will implement policies towards honoring them. The Asian cultures, including Japan, China, and Korea, highly respect the seniors and show utmost honor in taking care of the elderly. American seniors are subject to prejudice and stereotyping and are not often given the respect they deserve ( Giefing‐Kröll et al., 2015) . While families and religious value their elders, they are not accorded the same respect as elders in other regions. In the United Kingdom, the elderly are valued as an asset who are supported to enjoy full and positive lives in a family setting.
Several cultural traditions affect the treatments of immunosenescence based on how they take care of the seniors. For example, the stigma attached to this condition has been an obstacle for appropriate treatment, leaving the elderly lacking the necessary support for treatment. Individuals with immunosenescence have been associated with having the HIV/AIDS virus, which some cultures discriminate and stigmatize.
Media exposure is also an important aspect when it comes to health promotion for immunosenescence among the elderly population. The media plays a vital role in spreading the awareness of immunosenescence and help people understand its cause and impact on the health of the elderly ( McElhaney & Effros, 2009) . However, the media has not been an excellent partner in spreading immunosenescence awareness due to a lack of knowledge on the severity of the condition among the elderly.
The question of whether aging is a disease or not carries high normative significance. Some people believe that aging is a disease and is an appropriate target for medical intervention, while other cultures believe it is normal for older adults to feel weak ( Thewissen et al., 2007) . This perception affects how different cultures approach the treatment and response of the problem. For example, some cultures have labeled aging as a disease, which has been crucial in facilitating access to medical care. Other religions in the United States have different beliefs on aging and will not show enough respect towards them.
The conceptions and experiences of well-being vary across cultural contexts while tied to fundamental cultural differences. The independent cultural backgrounds in the United States and around the world influences how well they interpret this issue. Aging is a biological change that occurs in an individual over time, often involving a decline in function and processes common to all living things ( Giefing‐Kröll et al., 2015) . The immune system is affected by aging, and the immune response reduces, leading to high morbidity and reduced productivity. Aging is influenced by both nutritional and pharmacological interventions, which are primary medication for immunosenescence.
Conclusion
Biological aging describes the gradual decline in physiological functions and a corresponding increase in susceptibility to diseases and disabilities as individuals grow older. Although there has not been a one-size-fits-all explanation for the cause of biological aging, several works of research have identified errors in DNA and accumulated cellular damage to be the major factors for the degeneration of later-life. Discoveries in the area of i mmunosenescence would certainly enable humanity to live longer, healthier, and fulfilling lives. The benefits of such anti-aging interventions are not limited just to the wellbeing of the individuals, but they also touch on the broader society. Estimates of economic value due to increases in the health span of the elderly are generally positive. Increasing human health would cut on the health expenses and the money directed to alternative economic channels. The gains from a healthier workforce who remain employed for a long time, even beyond the ages of 65, would also attract economic largesse. To realize these and more benefits of longer health spans, scientists are continuously working on the anti-immunosenescence interventions. Yet, the search for reversing i mmunosenescence is fraught with divergent views and challenges, especially from the ethical and cultural perspectives. Part of the concerns is that the interventions used in the treatments for aging may be far-reaching. There are many uncertainties on what the treatments would have on human health and lifespan alike. More concerns are raised over minor factors such as personal identities, the ethical or cultural frameworks for the geroscience researches, and the degree of endorsement by the consumers and/ or policymakers. Geroscience has partly succeeded in the exploration of interventions for immunosenescence, but the fight for healthy aging is far from over.
References
Aiello, A., Farzaneh, F., Candore, G., Caruso, C., Davinelli, S., Gambino, C. M. & Accardi, G. (2019). The Immunosenescence and its Hallmarks: how to Oppose Ageing Strategically? A Review of Potential Options for Therapeutic Intervention. Frontiers in immunology , 10 , 2247.
Berrut, G., & de Decker, L. (2015). Immunosenescence: a review. Geriatrie et psychologie neuropsychiatrie du vieillissement , 13 , 7.
Costantini, E., D'Angelo, C., & Reale, M. (2018). The role of Immunosenescence in neurodegenerative diseases. Mediators of inflammation , 2018 .
Crooke, S. N., Ovsyannikova, I. G., Poland, G. A., & Kennedy, R. B. (2019). Immunosenescence and human vaccine immune responses. Immunity & Ageing , 16 (1), 25.
Duggal, N. A., Niemiro, G., Harridge, S. D., Simpson, R. J., & Lord, J. M. (2019). Can physical activity ameliorate immunosenescence and thereby reduce age-related multi-morbidity?. Nature Reviews Immunology , 19 (9), 563-572.
Fulop, T., Franceschi, C., Hirokawa, K., & Pawelec, G. (2009). Perspectives: is immunosenescence clinically relevant? In Handbook on Immunosenescence (pp. 1647-1648). Springer, Dordrecht.
Fulop, T., Larbi, A., Dupuis, G., Le Page, A., Frost, E. H., Cohen, A. A., ... & Franceschi, C. (2018). Immunosenescence and inflamm-aging as two sides of the same coin: friends or foes?. Frontiers in immunology , 8 , 1960.
Gems, D. (2011). Tragedy and delight: the ethics of decelerated ageing. Philosophical transactions of the royal society B: Biological Sciences , 366 (1561), 108-112.
Giefing‐Kröll, C., Berger, P., Lepperdinger, G., & Grubeck‐Loebenstein, B. (2015). How sex and age affect immune responses, susceptibility to infections, and response to vaccination. Aging cell , 14 (3), 309-321.
Isidori, A., Loscocco, F., Ciciarello, M., Corradi, G., Lecciso, M., Ocadlikova, D. ... & Curti, A. (2018). Immunosenescence and immunotherapy in elderly acute myeloid leukemia patients: Time for a biology-driven approach. Cancers , 10 (7), 211.
Lee, B. Y., Ercius, A. K., & Smith, K. J. (2009). A predictive model of the economic effects of an influenza vaccine adjuvant for the older adult (age 65 and over) population. Vaccine , 27 (16), 2251-2257.
McElhaney, J. E., & Effros, R. B. (2009). Immunosenescence: what does it mean to health outcomes in older adults? Current opinion in immunology , 21 (4), 418-424.
Pawelec, G. (2018). Age and immunity: what is "immunosenescence"?. Experimental gerontology , 105 , 4-9.
Shetty, A. K., Kodali, M., Upadhya, R., & Madhu, L. N. (2018). Emerging anti-aging strategies-scientific basis and efficacy. Aging and disease , 9 (6), 1165.
Thewissen, M., Somers, V., Venken, K., Linsen, L., Van Paassen, P., Geusens, P., ... & Stinissen, P. (2007). Analyses of immunosenescent markers in patients with autoimmune disease. Clinical immunology , 123 (2), 209-218.
Vaiserman, A., Koliada, A., & Lushchak, O. (2018). Developmental programming of aging trajectory. Ageing research reviews , 47 , 105-122.
