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Reductionism versus Systems Thinking in Aging Research
Published in Shamim I. Ahmad, Aging: Exploring a Complex Phenomenon, 2017
In an attempt to bridge the gap between these first two models of aging research (reductionist approach) and the third one which defines a more comprehensive, multidimensional view of aging (a “systems thinking” approach), I will now discuss the concept of Molecular Pathological Epidemiology (MPE), and how this may share elements with cybernetic and “wholistic” (as in “whole”) views on aging. A reductionist First or Second Phase Science model is at odds with a concept developed by Shuji Ogino, that of MPE [49]. MPE combines elements from epidemiology and pathology in order to study the heterogeneity and etiology of disease and degeneration. In this case, the focus is both at a microscopic (molecular and cellular) and macroscopic (organismal and population) levels. Therefore MPE may act as a link between reductionism and systems thinking perspectives. In this way, it is possible to form a more inclusive view of the different disease processes. In essence, MPE helps us study the influence of the environment on genetic factors, and it shares many frontiers with Social Genomics, although it is also focused on epidemiological matters. However, if we are using only a simplistic model to study aging, we may encounter problems such as an uncontrollable and unpredictable multiplication of random errors in the repair process which a theoretical antiaging drug/therapy may be associated with [50]. On the basis of principles developed within MPE, we may find that there are several inherently heterogeneous interacting pathological processes which may lead to disease. We cannot adequately predict, or even study, these multiple processes which can cause significant variations of diseases even in similar patients [51]. The net result is that in order for a therapy to be effective for any given patient, it is necessary to develop tailor-made interventions for each patient, and not rely on generic treatments. This may prove to be an impossible task [52]. It has been termed the “Precision Medicine Concept” or the “Unique Disease Principle,” which suggests that each individual patient exhibit unique disease profiles based on an interaction of genetic, epigenetic, and other factors such as cell interactions, nutrition, lifestyle, microbial exposure, social and racial elements, age differences, etc. All of these factors need to be taken into account in the designing and application of any putative anti-aging therapy. In other words, both the biological and the social/environmental elements need to be taken together, whereas currently the reductionist model of one “fit-all” therapy takes into account only the biological element.
Leveraging proteomics in orphan disease research: pitfalls and potential
Published in Expert Review of Proteomics, 2021
Daniela Braconi, Giulia Bernardini, Ottavia Spiga, Annalisa Santucci
Compelling evidence clearly shows that environmental factors such as diet, lifestyle, and microbiota can have pathogenic roles and affect multiple ‘ome’ repertoires in a variety of cell types. Hence, an interdisciplinary approach combining epidemiology, biostatistics, and bioinformatics could be a fruitful endeavor in the orphan disease field too, as recently exemplified in neoplastic and non-neoplastic diseases [168]. This idea has been conceptualized as ‘molecular pathological epidemiology,’ a hybrid field of pathology where knowledge of the genetic background and the environment is integrated to understand molecular pathologic changes observed, for instance, at the proteome and metabolome level [169]. In each individual, in fact, the development of a disease is determined by a combination of endogenous (including germlines and immunity) and exogenous factors, producing different molecular and pathological subtypes of the disease [170]. Though challenges are to be faced here, mainly due to the lack of scientists with such an interdisciplinary expertise, novel opportunities might arise: molecular pathological epidemiology is a versatile, genuinely method-based discipline that can be applied to any research area and, virtually, to all human diseases [169,171].
Promoting the value of precision medicine to the public: the power of storytelling
Published in Expert Review of Precision Medicine and Drug Development, 2018
The Genetics Home Reference has defined ‘precision medicine’ as ‘an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person’ [1]. While the concept is sound, most physicians may find it difficult to quantitatively assess an individual’s environment and lifestyle variations, short of obvious factors, such as smoking, lack of exercise, and poor dietary habits. The field of molecular pathological epidemiology has begun to link a patient’s environment and lifestyle to his disease management [2]. In contrast, there has been much progress in determining the role of germ-line and somatic mutations for the diagnosis and prevention of specific diseases, but especially for selecting the most appropriate therapeutic treatment. ‘Companion diagnostics’ usually refers to use of specific drugs or biologics to treat patients who have demonstrated the presence of a specific somatic variance in order to improve therapeutic efficacy. The adoption of ‘companion diagnostics’ continues at a reasonable pace. As of 27 April 2018, the FDA has approved 26 companion tests linked with therapeutics for treatment of various diseases, with several more in process [3]. Medical specialists such as oncologists, rheumatologists, and others who see these patients have been the drivers for the use of these special laboratory tests.
TIME (Tumor Immunity in the MicroEnvironment) classification based on tumor CD274 (PD-L1) expression status and tumor-infiltrating lymphocytes in colorectal carcinomas
Published in OncoImmunology, 2018
Tsuyoshi Hamada, Thing Rinda Soong, Yohei Masugi, Keisuke Kosumi, Jonathan A. Nowak, Annacarolina da Silva, Xinmeng Jasmine Mu, Tyler S. Twombly, Hideo Koh, Juhong Yang, Mingyang Song, Li Liu, Mancang Gu, Yan Shi, Katsuhiko Nosho, Teppei Morikawa, Kentaro Inamura, Sachet A. Shukla, Catherine J. Wu, Levi A. Garraway, Xuehong Zhang, Kana Wu, Jeffrey A. Meyerhardt, Andrew T. Chan, Jonathan N. Glickman, Scott J. Rodig, Gordon J. Freeman, Charles S. Fuchs, Reiko Nishihara, Marios Giannakis, Shuji Ogino
Our study has notable strengths including the use of a molecular pathological epidemiology database derived from two U.S. prospective cohort studies with long duration of follow-up.53,54 Integrated data on tumor molecular characteristics and pathological findings allowed us to comprehensively characterize TIME subtypes of colorectal cancer. Of note, our study population was derived from a large number of cases from hospitals located throughout the U.S., contributing to increased generalizability of our findings.