Systems Biology of Human Aging
Network Model
Biochemical and Physiological Interactions

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At first glance this wall chart looks like a complicated web. However, as a conceptual summary, in one view, we can see how most biogerontological processes relate to each other. Importantly, examination of these relationships allows us to pick out reasonably plausible causal chains of events. Within these chains, we can see age-related changes (or accumulations) that appear to be promising targets for future therapy development. Especially harmful is damage to the body's regeneration and repair systems, because they normally repair damage to other structures and systems. Repairing the repair systems should receive high priority in planning the development of new therapies. An important example is age-associated accumulation of lipofuscin inside the lysosomes inside neurons. This can block autophagic removal of damaged structures inside the cells. In this chart, we can follow several important pathways from age-associated causes down through the age-associated pathologies that result.

This symbolic diagram is not really a picture of a cell. It changes in scale from molecular events at the top, through whole cell activities in the middle, to tissue, organ, and whole body diseases at the bottom.
Thick horizontal borders separate transitions in scale. Intracellular events are described on the top left. Extracellular matrix and blood are described on the top right.
Colors have meaning, as indicated in the "Color Key".
Shapes have meanings described in the "Shape Key".
Solid boxes represent physical materials.
Slanted-roof boxes represent increase or decrease in quantities during aging.
Hatched boxes represent activities or processes.
Thin arrows represent causal sequences of events.
Thick arrows represent physical transport or movement.
A circle with an "X" inside represents inhibition of the indicated process; this might mark a candidate target for therapeutic intervention.
Tags pointing in from the far left and right represent environmental factors or interventions or hypothetical interventions.

ABBREVIATIONS: For a printable PDF with meanings of abbreviations used in this diagram: [ Click Here to download printable introductory text pages: "Abstract", "Getting Started", "Abbreviations", and "Acknowledgements and Citations." ==> chartintro.pdf 160 kB ]


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This Network Model of Human Senescence was compiled and arranged by John D. Furber, based upon information in research reports from many scientists. You may cite this chart as References and links to more information about these topics may be found at: Keywords may be searched at your favorite reference or search system. For example: A good, short review of aging mechanisms was published in the journal, Nature by Jan Vijg & Judith Campisi. (2008) Puzzles, promises and a cure for ageing. Nature, 454, 1065-1071.

Special thanks go to the following scientists for their helpful suggestions on earlier versions of this network diagram, which were used to update it to its current form:

(Alphabetical listing)
Arthur Balin, Joe Betts-Lacroix,
Robert Bradbury (deceased),
Ulf T. Brunk, Alexander Buerkle, Ashley I. Bush,
Irina Conboy, Michael Conboy, Richard G. Cutler,
Aubrey de Grey, Juraj Dzifcak,
Caleb Finch, Allen Herbst, Thomas E. Johnson,
James Joseph (deceased),
Pat Langley, George M. Martin,
Mark P. Mattson, Florian Muller,
Mark A. Smith (deceased),
Stanley Primmer, Stephen A. Racunas, Alexandra Stolzing,
Alexei Terman, Bill Vaughan, Michael Verdicchio


This Network Model has been used as the Basis
of Research and Writing by Others:


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  • [ Click Here to download the Wall Chart ==> furberchart.pdf ]
  • [ Click Here to download printable introductory text pages for display with the wall chart: "Abstract", "Getting Started", "Abbreviations", and "Acknowledgements and Citations." ==> chartintro.pdf 160 kB ]
  • [ Click Here to download the printable references, sources, and expansions of the text boxes: ==> chartrefs.pdf 139 kB ]


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Earlier versions of this network model were presented by John D. Furber in lectures or poster sessions at many meetings, including the following:

Please Send feedback, suggested references, and suggestions for improvements: Please email us if you see errors to correct, or if you can suggest ways to improve the clarity or utility of this Network Model as a tool for teaching or research. If you suggest a reference, please identify the box or boxes to which it applies (and the DATE version you are looking at), and a brief (1-3 sentences) summary of how this reference applies. Please also tell us if you are using this chart in your classroom, research institute, or clinic.
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