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Tower, J.

Publications and source records attributed to Tower, J..

2 recordsLinked to original sources

Selectively Advantageous Instability and Information Theory in Sex-specific Aging

Biological information is generally thought to be subject to selection for faithful maintenance. However, accurate preservation is often combined with regulated mechanisms that generate state change. Selectively advantageous instability (SAI) of biological information is modeled here as instability that is favored because useful alternatives become accessible. Modeling shows that active destabilization is favored above a threshold determined by environmental change, passive error, destabilization cost, and the relative adaptive targeting of active versus passive variation. When actively generated variation is sufficiently structured, selection simultaneously favors increased maintenance and increased active destabilization of the same information channel. This relationship is described as stabilization-destabilization complementarity. Shannon entropy quantifies uncertainty, whereas relative entropy quantifies mismatch between generated and fitness-relevant state distributions. Aging is not produced by reversible state-space exploration alone. Aging results when selected exploration also causes persistent or cumulative loss of maintained organization. Age and sex extensions show how delayed costs and shared genetic control can generate antagonistic pleiotropy and sexual conflict. A unified interpretation is provided in which SAI can be selected as a mechanism of adaptive state space exploration even when long term information displacement is costly.

systems biology↗

A multi-omic atlas in the African turquoise killifish reveals increased glucocorticoid signaling as a hallmark of brain aging

Aging is the leading risk factor for cognitive impairment and neurodegeneration, yet molecular changes that unfold in the brain over time, and how they drive this vulnerability, remain unclear. The naturally short-lived African turquoise killifish (Nothobranchius furzeri) offers a powerful model to understand brain aging on an accelerated timescale and test the impact of potential interventions. Here, we present a multi-omic atlas of brain aging of female and male African turquoise killifish from 2 independent genetic strains of different captive lifespans, encompassing single-nuclei RNA-seq, single nuclei ATAC-seq, and bulk ATAC-seq to capture transcriptional and regulatory changes. Interestingly, our atlas indicates that aging leads to a significant expansion of microglia numbers, regardless of sex or strain, which we independently validate using in-situ hybridization. In addition, we identify robust and conserved gene regulation changes, that are consistent with activation of glucocorticoid signalling as a hallmark (and potential driver) of vertebrate brain aging. Furthermore, pharmacological inhibition of glucocorticoid receptor activity starting at middle-age led to significant rescue of key molecular and cellular aging phenotypes. Thus, our study provides a powerful resource and framework to leverage the African turquoise killifish and rapidly uncover actionable pathways driving brain aging.

neuroscience↗