Interdisciplinary Topics in Gerontology

In this chapter, we describe in detail the age-dependent modifications of connective tissues, separately for their cellular and extracellular compartments. Cell aging was studied by the in vitro method established by Hayflick as well as by ex vivo explant cultures, and results with both methods are discussed. Follows then the description of age changes of macromolecular components of extracellular matrix as well as the decline with age of receptor-mediated cell-matrix interactions. These interactions mediated by several types of receptors, as integrins, the elastin receptor and others, play a crucial role for the definition and regulation of the differentiated cell phenotype...

Aging is characterized by a progressive decline in cellular function, organismal fitness and increased risk of age-associated diseases and death. One potential cause of aging is the progressive accumulation of dysfunctional mitochondria and oxidative damage with age. Considerable efforts have been made in our understanding of the role of mitochondrial dysfunction and oxidative stress in aging and age-associated diseases. This chapter outlines the interplay between oxidative stress and mitochondrial dysfunction, and discusses their impact on senescence, cell death, stem cell function, age-associated diseases and longevity...

This chapter is intended to outline the main results of a research trend realized by the author during the last 45 years, focused on the main role played by the cell membrane in the aging process. It is a very wide field; therefore, the reader cannot expect in this limited space a detailed description, but will be given a wide, interdisciplinary insight into the main facts and theories regarding cellular aging. The central idea described here is the concept called the membrane hypothesis of aging (MHA). The history, the chemical roots, physicochemical facts, biophysical processes, as well as the obligatory biochemical consequences are all touched in by indicating the most important sources of detailed knowledge for those who are more interested in the basic biology of the aging process...

Cell senescence is one of the major paradigms of aging research. It started with the demonstration by L. Hayflick of the limited number of divisions by normal, nontransformed cells, not shown by transformed malignant cells, this processes being largely regulated by the telomere-telomerase system. A complete renewal of this discipline came from the demonstration that cells can enter senescence at any time by an anti-oncogene-triggered pathway, enabling them to escape malignancy. The senescent cell became a major actor of the aging process, among others, by the acquisition of the senescence-associated secretory phenotype...

The observation that human fibroblasts have a limited number of cell population doublings in vitro led to the proposal that it is the expression of cellular aging. In vitro, the proliferation of human fibroblasts terminates with a postmitotic cell which was called senescent cell. Due to misinterpreted experiments, the latter was considered the hallmark of cellular aging, although obviously we do not age because our cells stop dividing. The so-called senescent cell has been the core of the investigation on cellular aging and of the theories proposed on the subject...

Evolutionary theories of aging explain why we age. These theories take into account the fact that, in the wild, mean lifespan of many species is usually shorter than it could be in protected environments. In such conditions, because most of animals die before reaching old age, there is no selection in favor or against alleles with effects at old age. Alleles with negative effects at this age can thus accumulate in successive generations, particularly if they also have positive effects at young age and are thus retained by selection...

Fifty years ago, it was demonstrated by Leonard Hayflick that human diploid fibroblasts grown in culture have a finite lifespan. Since that time, innumerable experiments have been published to discover the mechanism(s) that are responsible for this 'Hayflick limit' to continuous growth. Much new information has been gained, but there are certain features of this experimental system which have not been fully understood. One is the fact that different populations of the foetal lung strains WI-38 and MRC-5 have a range in division potential of at least a millionfold...

The incidence of cancer will increase dramatically among elderly people in the 21st century. The first French National Cancer Plan (2003-2006) with the French Ministry of Health supported the creation of 15 pilot coordination units in oncogeriatrics (UPCOG) in 13 out of the 27 French regions. The second French National Cancer Plan (2009-2013) continues to support oncogeriatrics. Based on evaluation of the pilot experiment in 2010, requirement specifications for an oncogeriatric coordination unit were defined and rolled out nationwide...

Older adults are at high risk for functional decline after a cancer diagnosis. Physiologic changes of aging which negatively impact body composition, strength, and fitness increase vulnerability to the development of short- and long-term disability when stressed with cancer burden and treatments. Treatment-associated physical disability impairs quality of life, limits therapeutic options, and contributes to the social and economic burden of cancer care in the elderly. Despite this, few clinical trials capture disability as an outcome or focus on whether it can be ameliorated in this population...

Geriatric oncology nursing is a specialization that requires unique knowledge and education to care for the older person diagnosed with cancer. Understanding principles of functioning in a multidisciplinary team setting, assessment of an older patient, and cancer-related issues are central elements of the role of the geriatric oncology nurse. Additionally, education of patients and families are important in helping the older person navigate the healthcare system. The purpose of this chapter is to review the current literature in geriatric oncology nursing...

Cancer in elderly patients is becoming a global issue, with the aging of the population and increased incidence of cancer with aging. Older patients with cancer have unique needs that can best be addressed by the integration of geriatrics principles and oncology care. Unfortunately, the worsening shortage of oncologists and geriatricians makes the care of the older patient with cancer increasingly challenging. Practical issues to consider when creating a geriatrics/oncology partnership include the available resources in terms of interdisciplinary team members, the patient population in need, and the ability to provide primary, consultative, and/or shared care...

Recent developments in oncogeriatric surgery focus on several items - preoperative risk estimation and identification of frail patients and optimalization of perioperative care. New screening tools are being evaluated and show promising results. There is increasing evidence that preoperative training of frail patients might decrease the rate of postoperative complications and increase survival. The recent trend towards individualized treatment schemes will certainly be of benefit for the elderly population...

The elderly comprise the majority of patients with cancer and are the recipients of the greatest amount of chemotherapy. Unfortunately, there is a lack of data to make evidence-based decisions with regard to chemotherapy. This is due to the minimal participation of older patients in clinical trials and that trials have not systematically evaluated chemotherapy. This chapter reviews the available information with regard to chemotherapy and aging. Due to the lack of prospective data, the conclusions and recommendations made are a consensus of the available information...

The incidence of cancer increases with advanced age and the majority of cancer deaths are in patients aged ≥ 65. The geriatric population is a heterogeneous group and a patient's chronologic age does not always correlate with underlying physiologic status. Oncologists need to be able to obtain information on physiologic and functional capacity in older patients in order to provide safe and effective treatment recommendations. The Comprehensive Geriatric Assessment (CGA) is a compilation of validated tools that predict morbidity and mortality in community-dwelling older adults...

The prognosis of acute myeloid leukemia (AML) in the elderly is poor with overall less than 5% of the patients expected to be alive after 5 years. In many studies, age was an independent poor prognostic factor. In the elderly, the frequency of secondary forms of AML, of unfavorable cytogenetics, expression of multidrug resistance genes in part explains the poor outcome. However, based on genetic and molecular studies, there is no evidence for specific biological features of the disease in the elderly. Host-related factors including comorbidity and reduced functional reserves also account for the severity of the disease...

The construct of frailty is germane to that of aging, but a clinical definition of frailty is still wanted. In the geriatric literature, frailty has been conceived in two different ways. The first one is a threshold beyond which the functional reserve of a person is critically reduced and the tolerance of stress negligible. The second is as a progressive reduction of functional reserve due to a progressive accumulation of deficit. In this construct it may be hard to distinguish frailty from aging. Neither concept has at present a clear application in the management of older cancer patients...

As older patients present with an average of three comorbidities beside their cancer, geriatric oncology can provide unique clues to translational research in aging and cancer. We illustrate this approach with the example of the metabolic syndrome and cancer. Epidemiologic and clinical cohorts highlighted an association between the metabolic syndrome and a higher risk and worse prognosis of various cancers. In a bedside-to-bench transition, this led to an interest in analyzing the potential mechanisms underlying this association...

The incidence and prevalence of most cancers increase with age. The immune system is a unique mechanism of defense against pathogens and possibly cancers, however there is a body of evidence that the immune system of the aged is eroded, a phenomenon termed immunosenescence. Each arm of the immune system, innate and adaptive, is altered with aging, contributing to increased tumorigenesis. Related to immunosenescence, a low-grade inflammation also develops with aging contributing also to increase carcinogenesis...

Cancer vaccination is less effective at old than at young age, due to T cell unresponsiveness. This is caused by various age-related changes of the immune system, such as lack of naïve T cells, defects in activation pathways of T cells and antigen-presenting cells, and age-related changes in the tumor microenvironment. Natural killer, natural killer T cells, and γδT cells of the innate immune system also change with age but these responses may be more susceptible for improvement than adaptive immune responses at older age...

Cancer is a devastating disease that increases exponentially with age. Cancer arises from cells that proliferate in an unregulated manner, an attribute that is countered by cellular senescence. Cellular senescence is a potent tumor-suppressive process that halts the proliferation, essentially irreversibly, of cells at risk for malignant transformation. A number of anti-cancer drugs have emerged that induce tumor cells to undergo cellular senescence. However, although a senescence response can halt the proliferation of cancer cells, the presence of senescent cells in tissues has been associated with age-related diseases, including, ironically, late-life cancer...