Despite increasing research efforts, there is a lack of consensus on defining aging or health. To understand the underlying processes, and to foster the development of targeted interventions towards increasing one’s health, there is an urgent need to find a broadly acceptable and useful definition of health, based on a list of (molecular) features; to operationalize features of health so that it can be measured; to identify predictive biomarkers and (molecular) pathways of health; and to suggest interventions, such as nutrition and exercise, targeted at putative causal pathways and processes. Based on a survey of the literature, we propose to define health as a state of an individual characterized by the core features of physiological, cognitive, physical and reproductive function, and a lack of disease. We further define aging as the aggregate of all processes in an individual that reduce its wellbeing , that is, its health or survival or both. We define biomarkers of health by their attribute of predicting future health better than chronological age. We define healthspan pathways as molecular features of health that relate to each other by belonging to the same molecular pathway. Our conceptual framework may integrate diverse operationalizations of health and guide precision prevention efforts.

Dispositions and tendencies feature significantly in the biomedical domain and therefore in representations of knowledge of that domain. They are not only important for specific applications like an infectious disease ontology, but also as part of a general strategy for modelling knowledge about molecular interactions. But the task of representing dispositions in some formal ontological systems is fraught with several problems, which are partly due to the fact that Description Logics can only deal well with binary relations. The paper will discuss some of the results of the philosophical debate about dispositions, in order to see whether the formal relations needed to represent dispositions can be broken down to binary relations. Finally, we will discuss problems arising from the possibility of the absence of realizations, of multi-track or multi-trigger dispositions and offer suggestions on how to deal with them.

Fighting the current COVID-19 pandemic, we must not forget to prepare for the next. Since elderly and frail people are at high risk, we wish to predict their vulnerability, and intervene if possible. For example, it would take little effort to take additional swabs or dried blood spots. Such minimally-invasive sampling, exemplified here during screening for potential COVID-19 infection, can yield the data to discover biomarkers to better handle this and the next respiratory disease pandemic. Longitudinal outcome data can then be combined with other epidemics and old-age health data, to discover the best biomarkers to predict (i) coping with infection & inflammation and thus hospitalization or intensive care, (ii) long-term health challenges, e.g. deterioration of lung function after intensive care, and (iii) treatment & vaccination response. Further, there are universal triggers of old-age morbidity & mortality, and the elimination of senescent cells improved health in pilot studies in idiopathic lung fibrosis & osteoarthritis patients alike. Biomarker studies are needed to test the hypothesis that resilience of the elderly during a pandemic can be improved by countering chronic inflammation and/or removing senescent cells. Our review suggests that more samples should be taken and saved systematically, following minimum standards, and data be made available, to maximize healthspan & minimize frailty, leading to savings in health care, gains in quality of life, and preparing us better for the next pandemic, all at the same time.

BackgroundThe concept of function is central to both biology and technology, but neither in philosophy nor in formal ontology is there a generally accepted theory of functions. In particular, there is no consensus how to include functions into a top-level ontology or whether to include them at all.MethodsWe first review current conceptions of functions in philosophy and formal ontology and evaluate them against a set of criteria. These evaluation criteria are derived from a synopsis of theoretical and practical requirements that have been suggested for formal accounts of functions. In a second step, we elucidate in particular the relation between functions and dispositions.ResultsWe argue that functions should not be taken as a subtype of dispositions. The strongest reason for this is that any view that identifies functions with certain dispositions cannot account for malfunctioning, which is having a function but lacking the matching disposition. As a result, we suggest a cross-classification of realizables with dispositions supervening on the physical structure of their bearer, whereas both functions and roles also have some external grounding. While bearers can survive the gain, loss and change of roles, functions are rigid properties that are essentially connected to their particular bearers. Therefore, Function should not be regarded as a subtype of Disposition; rather, the classes of functions and dispositions are disjoint siblings of Realizable.

Disposition-the tendency of something to act in a certain manner under given circumstances resulting from natural constitution; nature; quality; orderly arrangement. It is not clear what the semicolons are intended to signify in this definition. The terms that are enlisted with semicolons between them do not seem to be synonymous: a nature is distinct from a quality, and both are distinct from an orderly arrangement. Thus, contrary to the official intention of the NCIT, 6 the term "disposition" in the NCIT seems not to signify a unique thing, but rather a somewhat confused bundle of things. Moreover, the NCIT subsumes Disposition under the heading Conceptual Entity and not, as one would expect, under the heading Property or Attribute. Surprisingly again, NCIT contains no sub-items of Disposition, though it seems to be obvious that all tendencies "to act in a certain manner under given circumstances resulting from natural constitution" (for example, Tumorigenicity or Lipophilicity) should be listed as sub-items here. Given the widespread occurrence of words like "tendency" and "disposition" in the medical literature it would be very desirable for the terminologies to reflect this importance by adequately representing these subtypes. This is because one of the most important uses of such terminologies is the annotation of research literature in order to enhance information retrieval. Also, the truth of statements like Tumorigenicity is-a Tendency should be reflected in subsumption relations between the corresponding terms in order to enhance automated reasoning. 1.2 Previous Work Like dispositions, tendencies are causal properties. Standard accounts characterise a tendency as "an entity which can be counteracted by other tendencies" or as "a potentiality which may be exercised without being realized". 7 The first of these characterisations being circular and the second introducing three new undefined terms, these definitions are insufficiently rigorous for the purposes of information systems which are designed to support computational reasoning. Thus we have to go further. While discussion of tendencies can be traced back at least to Aristotle and to what he says on dynamis, physis, and hexis, 8 there is comparatively little discussion of tendencies in the recent philosophical literature. 9 An exception is the work

ObjectiveTo (1) evaluate the GoodOD guideline for ontology development by applying the OQuaRE evaluation method and metrics to the ontology artefacts that were produced by students in a randomized controlled trial, and (2) informally compare the OQuaRE evaluation method with gold standard and competency questions based evaluation methods, respectively.BackgroundIn the last decades many methods for ontology construction and ontology evaluation have been proposed. However, none of them has become a standard and there is no empirical evidence of comparative evaluation of such methods. This paper brings together GoodOD and OQuaRE. GoodOD is a guideline for developing robust ontologies. It was previously evaluated in a randomized controlled trial employing metrics based on gold standard ontologies and competency questions as outcome parameters. OQuaRE is a method for ontology quality evaluation which adapts the SQuaRE standard for software product quality to ontologies and has been successfully used for evaluating the quality of ontologies.MethodsIn this paper, we evaluate the effect of training in ontology construction based on the GoodOD guideline within the OQuaRE quality evaluation framework and compare the results with those obtained for the previous studies based on the same data.ResultsOur results show a significant effect of the GoodOD training over developed ontologies by topics: (a) a highly significant effect was detected in three topics from the analysis of the ontologies of untrained and trained students; (b) both positive and negative training effects with respect to the gold standard were found for five topics.ConclusionThe GoodOD guideline had a significant effect over the quality of the ontologies developed. Our results show that GoodOD ontologies can be effectively evaluated using OQuaRE and that OQuaRE is able to provide additional useful information about the quality of the GoodOD ontologies.

Statements about the behavior of biochemical entities (e.g., about the interaction between two proteins) abound in the literature on molecular biology and are increasingly becoming the targets of information extraction and text mining techniques. We show that an accurate analysis of the semantics of such statements reveals a number of ambiguities that have to be taken into account in the practice of biomedical ontology engineering: such statements can not only be understood as event reporting statements, but also as ascriptions of dispositions or tendencies that may or may not refer to collectives of interacting molecules or even to collectives of interaction events. Molecular interactions: On the ambiguity of ordinary statements CT (SNOMED, 2008)). Especially the development of medical terminology systems has been mainly committed to traditions of semantic networks, lexical semantics, and cognitive science. Thus rather than being construed as describing real world entities by means of logical expressions, the focus has largely been set to concepts (i.e., representations of word meanings or mental representations) by means of conceptual relations. On this assumption, "Lmo-2 interacts with Elf-2" would simply signify that there is some plausible linkage between the concepts (conceived of as mental representations) "Interaction", "Lmo-2" and "Elf-2". As much as this approach might be adequate for structuring knowledge about the world by means of natural language or some kind of abstraction (e.g., in bibliographic thesauri, such as the Medical Subject Headings (MeSH, 2007)), it fails where exact statements and reasoning about biological entities, such as molecules, functions, or pathways are required.Interestingly enough, scientists and other human agents are perfectly able to communicate by means of such statements, and they obviously agree on the referents (the entities in the world) which are denoted by linguistic expressions like "Lmo-2 interacts with Elf-2". It seems that the semantic underdeterminations of these statements are of minor importance for their communication. From a formal ontology perspective, however, one has to take into account that "Lmo-2 interacts with Elf-2" may have more than one possible interpretation and thus more than one formalization in, say, first order predicate logic. In formally representing the meaning of such statements, we have thus to make explicit what the speakers or authors precisely wanted to express.In this paper we will demonstrate that even the formalization of an apparently simple but prototypical statement about protein interaction like "Lmo-2 interacts with Elf-2" may uncover totally different ontological presuppositions.

The molecular basis of aging and of aging-associated diseases is being unraveled at an increasing pace. An extended healthspan, and not merely an extension of lifespan, has become the aim of medical practice. However, a precise definition of health and healthspan is not straightforward, and the causal molecular basis of health "per se" is largely unknown. Here, we define health based on the absence of diseases and dysfunctions. Based on an extensive review of the literature, in particular for humans and C. elegans, we compile a list of features of health and of the genes associated with them. Clusters of these genes based on molecular interaction data give rise to maps of healthspan pathways for humans, featuring the themes transcription initiation, proliferation and cholesterol/lipid processing, and for C. elegans, featuring the themes immune response, mitochondrion and biosynthesis based on genetic and compound intervention data, and lipids, biosynthesis and transcription based on WormBase compound intervention data. Overlaying healthspan-related gene expression data (describing effects of metabolic intervention associated with improvements in health) onto the aforementioned healthspan pathway maps, we observe the downregulation of Notch signalling in humans and of proliferation/cell-cycle in C. elegans. The former reflects the proinflammatory role of the Notch pathway. We identify transcription, proliferation/biosynthesis and lipids as a common theme on the annotation level, and proliferation-related kinases on the gene/protein level. Our literature-based data corpus, including visualization, is available as a reference for future investigations, at http://www.h2020awe.eu/index.php/pathways/.