Speaker
Description
Nearly every physiological function declines with age, as risk of death, disability and chronic disease rises exponentially. Whereas many specific diseases have well-characterized biomarkers and diagnostic thresholds, age-related decline is difficult to quantify and often appears as small, ambiguous changes across many biomarkers. We hypothesized that these changes reflect collective, pathological behaviours that push health systems away from stability, i.e. homeostasis. We used linear order eigen-analysis to characterize these deviations in terms of stability and fixed point drift. We then analyzed associations with adverse outcomes including death and chronic disease – that we surmise occur after deviations reach a tipping point.
We used longitudinal health data from multiple species and datasets\cite{Pridham2023-pi,Pridham2024-ql,Pridham2024-in} to estimate interaction networks to linear order. Stability analysis using the eigen-decomposition consistently revealed that health biomarker data are stable, and demonstrate two characteristic behaviours. The position of the fixed point drifts with age, a phenomenon we call “mallostasis”, and variance accumulates along weakly-stable dimensions, a phenomenon we call “stochastic accumulation”. Each network has only a few such dimensions but they dominate risk of adverse outcomes. Analysis of these dimensions shows that each dimension shares similarities to a different medical syndrome. We discuss the dynamical behaviour and utility of eigen-states for characterizing overall health.
Bibliography
@article{Pridham2023-pi,
title = "Network dynamical stability analysis reveals key “mallostatic”
natural variables that erode homeostasis and drive age-related
decline of health",
author = "Pridham, Glen and Rutenberg, Andrew D",
journal = "Sci. Rep.",
publisher = "Nature Publishing Group",
volume = 13,
number = 1,
pages = "1--12",
month = dec,
year = 2023,
url = "https://www.nature.com/articles/s41598-023-49129-7",
doi = "10.1038/s41598-023-49129-7",
issn = "2045-2322,2045-2322"
}
@article{Pridham2024-in,
title = "Dynamical network stability analysis of multiple biological ages
provides a framework for understanding the aging process",
author = "Pridham, Glen and Rutenberg, Andrew D",
journal = "J. Gerontol. A Biol. Sci. Med. Sci.",
month = jan,
year = 2024,
url = "http://dx.doi.org/10.1093/gerona/glae021",
keywords = "biological age; complexity; eigen analysis; systems biology",
doi = "10.1093/gerona/glae021",
pmid = 38206765,
issn = "1079-5006,1758-535X"
}
@article{Pridham2024-ql,
title = "Systems-level health of patients living with end-stage kidney
disease using standard lab values",
author = "Pridham, Glen and Tennankore, Karthik K and Rockwood, Kenneth
and Worthen, George and Rutenberg, Andrew D",
journal = "arXiv [q-bio.QM]",
month = may,
year = 2024,
url = "http://arxiv.org/abs/2405.20523",
archivePrefix = "arXiv",
primaryClass = "q-bio.QM",
eprint = "2405.20523"
}
