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Aging and disease
Review Article |
Health and Aging: Unifying Concepts, Scores, Biomarkers and Pathways
Georg Fuellen1,*, Ludger Jansen2,*, Alan A. Cohen3, Walter Luyten4, Manfred Gogol5, Andreas Simm6, Nadine Saul7, Francesca Cirulli8, Alessandra Berry8, Peter Antal9,10, Rüdiger Köhling11, Brecht Wouters12, Steffen Möller1
1Rostock University Medical Center, Institute for Biostatistics and Informatics in Medicine and Aging Research (IBIMA), Rostock, Germany.
2 Institute of Philosophy, University of Rostock, Germany.
3Department of Family Medicine, University of Sherbrooke, Sherbrooke, Canada.
4KU Leuven, Department of Pharmaceutical and Pharmacological Sciences, Leuven, Belgium.
5Institute of Gerontology, University Heidelberg, Germany.
6Department of Cardiac Surgery, Medical Faculty, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
7Humboldt-University of Berlin, Institute of Biology, Berlin, Germany.
8Center for Behavioral Sciences and Mental Health, Istituto Superiore di Sanità, Italy.
9Budapest University of Technology and Economics, Budapest, Hungary.
10Abiomics Europe Ltd., Hungary.
11Rostock University Medical Center, Institute for Physiology, Rostock, Germany.
12KU Leuven, Department of Biology, Leuven, Belgium
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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.

Keywords terminology      health      aging      biological age      wellbeing      biomarker     
Corresponding Authors: Georg Fuellen,Ludger Jansen   
Just Accepted Date: 19 November 2018  
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Georg Fuellen
Ludger Jansen
Alan A. Cohen
Walter Luyten
Manfred Gogol
Andreas Simm
Nadine Saul
Francesca Cirulli
Alessandra Berry
Peter Antal
Rüdiger Köhling
Brecht Wouters
Steffen Möller
Cite this article:   
Georg Fuellen,Ludger Jansen,Alan A. Cohen, et al. Health and Aging: Unifying Concepts, Scores, Biomarkers and Pathways[J]. Aging and disease, 10.14336/AD.2018.1030
URL:     OR
StateTime periodUnderlying biological processesPredictor of future state
healthhealthspanhealthspan-enhancing processeshealth biomarkers
survivallifespanlifespan-enhancing processessurvival biomarkers
wellbeing“wellspan”wellspan-enhancing processesbiological age
… and their
illbeing“illspan”aging processes
baseline organismal statechronological timeaverage biological processeschronological age
Table 1  Framework of definitions.
Featurelimited to speciespathologicalReferences
physiological function
stress resistance[17-21], cf.
thermo-tolerance (=heat shock tolerance)[22, 23]
hypoxic stress tolerance[24, 25]
osmotic stress tolerance[26]
oxidative stress tolerance[19, 23, 27]
metabolic status / homeostasisxcf.[2], cf. [28 29]
redox status / homeostasisx[30, 31]
immune status / homeostasisxcf. [20, 32]
physical & cognitive function (=strength and cognition)
motivated/stimulated locomotion(worm)[33]
(motor) balance, dexterityhuman/mouse[34-38]
muscle/neuronal/intestinal integrityx[39-41]
physical function (=strength)
[unmotivated/unstimulated] locomotioncf. [18, 20, 42, 43]
grip strengthhuman/mousecf. [20, 44, 45]
pharyngeal pumpingworm[18, 22, 46, 47]
gait speed, chair risinghuman/ (mouse)cf. [20, 48, 49]
muscle integrityx[40, 41]
cognitive function (=cognition)
sensory perceptioncf. [20, 50-52]
(short-term) memory,
processing speed
(human/ mouse)[53-56]
sleep, cardiac rhythmcf. [20, 57]
executive/verbal functionhuman/ mouse[58, 59]
neuronal integrityx[60]
reproductive function
number of offspring[61-64]
offspring health/survival[65, 66]
lack of frailty, Healthy Aging Index (and similar), allostatic load; lack of physiological dysregulation, self-reported health, quality of life(human)[2, 67-74]
(prodromal) organ/physiological function (heart/cardiovascular, neurological, etc.)
(prodromal) paralysis, protein aggregation/plaques
human/animal modelxcf. [20, 75, 76]
lack of disease and medications(human)e.g., [77, 78]
Table 2  Features contributing to a definition of health.
Table 2  includes dysfunctions, as well as various integrative approaches towards listing and indexing them, such as (lack of) frailty, “healthy aging” indices and the like. Such indices often include features on various levels of abstraction, but a rigorous justification for a specific selection of features is usually lacking. For example, frailty is defined as a state of reduced physiological fitness that includes multimorbidity, functional limitation, and geriatric syndromes, representing a compendium of interacting factors contributing to poorer health outcomes [80]. There are two more widespread definitions of frailty by [67, 68], but there is still a lack of consensus [82]. Further indices were introduced with an emphasis on “healthy” or “successful” aging, for example, the Healthy Aging Index by [69], the Successful Aging Index by [70], or the Healthy Aging Score by [71]. These indices include features from the sociodemographic domain partly based on self-assessment, disease-related scores such as disease counts, some laboratory markers such as blood pressure, and some examination scores such as the Mini-Mental State Examination test result. As another example of an integrative concept, allostatic load is based on laboratory markers [72]. A lot more indexes were developed, recently reviewed by [83], most recently encompassing multiple blood-based biomarkers [84], clinical and blood-based biomarkers [85, 86], functional measures and questionnaires [87], multimorbidity [88], or combinations of these [89].
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