Gordleeva, Susanna;
Kanakov, Oleg;
Ivanchenko, Mikhail;
Zaikin, Alexey;
Franceschi, Claudio;
(2020)
Brain aging and garbage cleaning : Modelling the role of sleep, glymphatic system, and microglia senescence in the propagation of inflammaging.
Seminars in Immunopathology
, 42
(5)
pp. 647-665.
10.1007/s00281-020-00816-x.
Preview |
PDF
revisionOK.pdf - Accepted Version Download (4MB) | Preview |
Abstract
Brain aging is a complex process involving many functions of our body and described by the interplay of a sleep pattern and changes in the metabolic waste concentration regulated by the microglial function and the glymphatic system. We review the existing modelling approaches to this topic and derive a novel mathematical model to describe the crosstalk between these components within the conceptual framework of inflammaging. Analysis of the model gives insight into the dynamics of garbage concentration and linked microglial senescence process resulting from a normal or disrupted sleep pattern, hence, explaining an underlying mechanism behind healthy or unhealthy brain aging. The model incorporates accumulation and elimination of garbage, induction of glial activation by garbage, and glial senescence by over-activation, as well as the production of pro-inflammatory molecules by their senescence-associated secretory phenotype (SASP). Assuming that insufficient sleep leads to the increase of garbage concentration and promotes senescence, the model predicts that if the accumulation of senescent glia overcomes an inflammaging threshold, further progression of senescence becomes unstoppable even if a normal sleep pattern is restored. Inverting this process by "rejuvenating the brain" is only possible via a reset of concentration of senescent glia below this threshold. Our model approach enables analysis of space-time dynamics of senescence, and in this way, we show that heterogeneous patterns of inflammation will accelerate the propagation of senescence profile through a network, confirming a negative effect of heterogeneity.
| Type: | Article |
|---|---|
| Title: | Brain aging and garbage cleaning : Modelling the role of sleep, glymphatic system, and microglia senescence in the propagation of inflammaging |
| Location: | Germany |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1007/s00281-020-00816-x |
| Publisher version: | https://doi.org/10.1007/s00281-020-00816-x |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions. |
| Keywords: | Aging, Cell, Glymphatic system, Inflammaging, Microglia, Senescence, Sleep, Waste solutes |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health > Womens Cancer |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10165112 |
Archive Staff Only
 |
View Item |
