The Human Body as a Super Network: Digital Methods to Analyze the Propagation of Aging

Abstract

Biological aging is a complex process involving multiple biological processes. These can be understood theoretically though considering them as individual networks-e.g., epigenetic networks, cell-cell networks (such as astroglial networks), and population genetics. Mathematical modeling allows the combination of such networks so that they may be studied in unison, to better understand how the so-called "seven pillars of aging" combine and to generate hypothesis for treating aging as a condition at relatively early biological ages. In this review, we consider how recent progression in mathematical modeling can be utilized to investigate aging, particularly in, but not exclusive to, the context of degenerative neuronal disease. We also consider how the latest techniques for generating biomarker models for disease prediction, such as longitudinal analysis and parenclitic analysis can be applied to as both biomarker platforms for aging, as well as to better understand the inescapable condition. This review is written by a highly diverse and multi-disciplinary team of scientists from across the globe and calls for greater collaboration between diverse fields of research.

Keywords: aging; digital medicine; inflammaging; network analysis; propagation of aging.

Figure 1

The seven pillars of aging according to Kennedy et (; blue outer nodes) are connected, such that perturbation in one pillar can affect each other pillar. The impairment of one or more pillars results in a chronic pro-inflammatory status—inflammaging. Inflammaging in a single part of the body can have distal effects on other systems (central circle) and thus can propagate aging. Studying the interaction of all these systems requires a systems biology approach. Given that each pillar or biological process can be represented by its network, this requires a network-of-networks solution.

Figure 2

Neuronal networks—cell types and factors interacting with each other affect age-related diseases. There are three main types of cells within neural cellular networks. A neuron or nerve cell is an electrically excitable cell that communicates with other neurons via specialized connections called synapses. They are the basic (functional and structural) unit of nervous tissue and the central nervous system (CNS). Astrocytes support neuronal function by providing essential structural and nutritional support, neurotransmitter trafficking and recycling and may also contribute to brain information processing. Astrocytes function as versatile metabolic sensors of CNS milieu and play an important role in the maintenance of brain metabolic homeostasis (for a recent review see Marina et al., 2018). Microglia are the only immune cells that permanently reside in the CNS. In the past decade, studies on microglia have expanded from investigating their function as resident macrophages of the brain and mediators of injury, neuroinflammation and neurodegeneration (reviewed in Salter and Stevens, ; Tay et al., 2017) to understanding their origins and non-immunological roles in the CNS. Networks of these cells are under the influence of different factors affecting the development of age-related diseases (pink arrows) and are supporting their metabolism by the interchange of metabolic products with blood vessels.