Modeling the Effects of a Simple Immune System and Immunodeficiency on the Dynamics of Conjointly Growing Tumor and Normal Cells

In this paper, we develop a theoretical contribution towards the understanding of the complex behavior of conjoint tumor-normal cell growth under the influence of immuno-chemotheraputic agents under simple immune system response. In particular, we consider a core model for the interaction of tumor cells with the surrounding normal cells. We then add the effects of a simple immune system, and both immune-suppression factors and immuno-chemotherapeutic agents as well. Through a series of numerical simulations, we illustrate that the interdependency of tumor-normal cells, together with choice of drug and the nature of the immunodeficiency, leads to a variety of interesting patterns in the evolution of both the tumor and the normal cell populations

Shortest-Path Network Analysis Is a Useful Approach toward Identifying Genetic Determinants of Longevity

Background Identification of genes that modulate longevity is a major focus of aging-related research and an area of intense public interest. In addition to facilitating an improved understanding of the basic mechanisms of aging, such genes represent potential targets for therapeutic intervention in multiple age-associated diseases, including cancer, heart disease, diabetes, and neurodegenerative disorders. To date, however, targeted efforts at identifying longevity-associated genes have been limited by a lack of predictive power, and useful algorithms for candidate gene-identification have also been lacking. Methodology/Principal Findings We have utilized a shortest-path network analysis to identify novel genes that modulate longevity in Saccharomyces cerevisiae. Based on a set of previously reported genes associated with increased life span, we applied a shortest-path network algorithm to a pre-existing protein–protein interaction dataset in order to construct a shortest-path longevity network. To validate this network, the replicative aging potential of 88 single-gene deletion strains corresponding to predicted components of the shortest-path longevity network was determined. Here we report that the single-gene deletion strains identified by our shortest-path longevity analysis are significantly enriched for mutations conferring either increased or decreased replicative life span, relative to a randomly selected set of 564 single-gene deletion strains or to the current data set available for the entire haploid deletion collection. Further, we report the identification of previously unknown longevity genes, several of which function in a conserved longevity pathway believed to mediate life span extension in response to dietary restriction. Conclusions/Significance This work demonstrates that shortest-path network analysis is a useful approach toward identifying genetic determinants of longevity and represents the first application of network analysis of aging to be extensively validated in a biological system. The novel longevity genes identified in this study are likely to yield further insight into the molecular mechanisms of aging and age-associated disease

Chemotherapy in conjoint aging-tumor systems: some simple models for addressing coupled aging-cancer dynamics

Background In this paper we consider two approaches to examining the complex dynamics of conjoint aging-cancer cellular systems undergoing chemotherapeutic intervention. In particular, we focus on the effect of cells growing conjointly in a culture plate as a precursor to considering the larger multi-dimensional models of such systems. Tumor cell growth is considered from both the logistic and the Gompertzian case, while normal cell growth of fibroblasts (WI-38 human diploid fibroblasts) is considered as logistic only. Results We demonstrate, in a simple approach, how the interdependency of different cell types in a tumor, together with specifications of for treatment, can lead to different evolutionary patterns for normal and tumor cells during a course of therapy. Conclusions These results have significance for understanding appropriate pharmacotherapy for elderly patients who are also undergoing chemotherapy

Applications to Aging Networks

This chapter introduces network concepts, and focuses on the application of the material in the previous chapter to the study of systems biology of aging. In particular, the study of aging networks in two sample species: Caenorhabditis elegans and Saccharomyces cerevisiae are used as an example of the method

TransPanthers: the greying of transgender and the law

Aging is a universal normalising process. No gender identity, no body form, no sex/sexuality is necessarily fixed in time and none of these facets of the human spirit are invulnerable to the ongoing processes of aging. Aging unites us in a way that no other process can. It is universal and inevitable. The emergence of a vocal population of transgender individuals of all ages mandates that we address the problems of aging in this population. The combined stigma of being elderly and transgender can serve as a strong traumatising force in the lives of such individuals. In this article, we focus on the interaction of aging, non-normative body forms and identities, and the law

Modeling the Effects of a Simple Immune System and Immunodeficiency on the Dynamics of Conjointly Growing Tumor and Normal Cells

In this paper, we develop a theoretical contribution towards the understanding of the complex behavior of conjoint tumor-normal cell growth under the influence of immuno-chemotheraputic agents under simple immune system response. In particular, we consider a core model for the interaction of tumor cells with the surrounding normal cells. We then add the effects of a simple immune system, and both immune-suppression factors and immuno-chemotherapeutic agents as well. Through a series of numerical simulations, we illustrate that the interdependency of tumor-normal cells, together with choice of drug and the nature of the immunodeficiency, leads to a variety of interesting patterns in the evolution of both the tumor and the normal cell populations.</p

Growth induced buckling instability of anisotropic tube and its application in wound edge instability

Fiber reinforced anisotropic material abounds in biological world. It has been demonstrated in previous theoretical and experimental works that growth of biological soft tubular tissue plays a significant role in morphogenesis and pathology. Here we investigate growth-induced buckling of anisotropic cylindrical tissue, focusing on the effects of type of growth(constraint/unconstraint, isotropic/anisotropic), fiber property(orientation, density and strength), geometry and any interaction between these factors. We studied one-layer and two-layer models and obtained a rich spectrum of results. For one-layer model, we demonstrate that circumferential fiber orientation has a consistent stabilizing effect under various scenarios of growth. Higher fiber density has a destabilizing effect by disabling high-mode buckling. For two-layer model, we found that critical buckling strain at inner boundary is an invariant under same isotropic growth rate ratio between inner/ outer layer(g1 /g0). Then we applied our model to wound healing and illustrate the effects of skin residual stress, fiber property, proliferation region width and wound size on the wound edge stability. We conclude that fiber-reinforcement is an important factor to consider when investigating growth induced instability of anisotropic soft tissue

Impact of Anticipated Bias from Healthcare Professionals on Perceived Successful Aging Among Transgender and Gender Nonconforming Older Adults

Purpose: Transgender and gender nonconforming (TGNC) persons have routinely experienced high rates of violence and discrimination. Discrimination in healthcare can affect the ability of TGNC persons to age successfully as it often deters them from seeking care. The purpose of this study was to determine if anticipation of bias from healthcare professionals, as well as other variables, predicted perceived successful aging in a sample of TGNC adults. Methods: A total of 384 (of the original 1963) participants older than 50 years completed the relevant parts of an 83-item online survey as part of the Trans MetLife Survey on Later-Life Preparedness and Perceptions in Transgender-Identified Individuals. Results: Larger social support networks and higher levels of confidence that a healthcare professional will treat them with dignity and respect as a TGNC person at the end of their life were associated with increased odds of perceiving that they were aging successfully. Conclusion: With high rates of discrimination and prejudice toward TGNC persons in various contexts (e.g., healthcare, education, and housing), it is imperative that practitioners, researchers, policymakers, and institutions work together to eradicate healthcare disparities, promote social change, and support an environment that encourages successful aging. This calls for a coordinated, proactive outreach effort to put trust back into a system that has historically let down an entire subset of the population