Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Fundamental Clock of Biological Aging: Convergence of Molecular, Neurodegenerative, Cognitive, and Psychiatric Pathways: Non-Equilibrium Thermodynamics Meet Psychology

Version 1 : Received: 4 November 2021 / Approved: 8 November 2021 / Online: 8 November 2021 (13:08:58 CET)

How to cite: Dyakin, V.V.; Dyakina-Fagnano, N.V.; McIntire, L.B.; Uversky, V.N. Fundamental Clock of Biological Aging: Convergence of Molecular, Neurodegenerative, Cognitive, and Psychiatric Pathways: Non-Equilibrium Thermodynamics Meet Psychology. Preprints 2021, 2021110138 (doi: 10.20944/preprints202111.0138.v1). Dyakin, V.V.; Dyakina-Fagnano, N.V.; McIntire, L.B.; Uversky, V.N. Fundamental Clock of Biological Aging: Convergence of Molecular, Neurodegenerative, Cognitive, and Psychiatric Pathways: Non-Equilibrium Thermodynamics Meet Psychology. Preprints 2021, 2021110138 (doi: 10.20944/preprints202111.0138.v1).

Abstract

In humans, age-associated degrading changes are observed in molecular and cellular processes underly the time-dependent decline in spatial navigation, time perception, cognitive and psy-chological abilities, and memory. Cross talk of biological, cognitive, and psychological clocks provides an integrative contribution to healthy and advanced aging. At the molecular level, ge-nome, proteome, and lipidome instability are widely recognized as the primary causal factors in aging. We narrow attention to the roles of protein aging linked to prevalent amino acids chirali-ty, enzymatic and spontaneous (non-enzymatic) post-translational modifications (PTMs SP), and non-equilibrium phase transitions. The homochirality of protein synthesis, resulting in the steady-state non-equilibrium condition of protein structure, makes them prone to multiple types of enzymatic and spontaneous PTMs, including racemization and isomerization. Spontaneous racemization leads to the loss of the balanced prevalent chirality. Advanced biological aging re-lated to irreversible PTMs SP has been associated with the nontrivial interplay between poor so-matic and mental health conditions. Through stress response systems (SRS), the environmental and psychological stressors contribute to the age-associated “collapse” of protein homochirality. The role of prevalent protein chirality and entropy of protein folding in biological aging is mainly overlooked. In a more generalized context, the time-dependent shift from enzymatic to the non-enzymatic transformation of biochirality might represent an important and yet un-der-appreciated hallmark of aging.

Keywords

spontaneous; non-enzymatic; post translational modifications; racemization; biological clock; natural selection; allostatic load; psychological aging; psychological stress; stress response sys-tem; phase transitions.

Subject

BIOLOGY, Physiology

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