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

2021 ◽  
Author(s):  
Victor Vasilyevich Dyakin ◽  
Nika Victorovna Dyakina-Fagnano ◽  
Laura Beth McIntire ◽  
Vladimir Nikolaevich Uversky
Keyword(s):  
Equilibrium Phase ◽  
Time Dependent ◽  
Biological Aging ◽  
Post Translational Modifications ◽  
Cellular Processes ◽  
Enzymatic Transformation ◽  
Psychological Stressors ◽  
Protein Aging ◽  
Response Systems ◽  
Non Equilibrium

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.

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

2021 ◽  
Vol 23 (1) ◽  
pp. 285
Author(s):  
Victor V. Dyakin ◽  
Nuka V. Dyakina-Fagnano ◽  
Laura B. Mcintire ◽  
Vladimir N. Uversky
Keyword(s):  
Equilibrium Phase ◽  
Time Dependent ◽  
Biological Aging ◽  
Cellular Processes ◽  
Enzymatic Transformation ◽  
Psychological Stressors ◽  
Protein Aging ◽  
Response Systems ◽  
Aging Health ◽  
Non Equilibrium

In humans, age-associated degrading changes, widely observed in molecular and cellular processes underly the time-dependent decline in spatial navigation, time perception, cognitive and psychological abilities, and memory. Cross-talk of biological, cognitive, and psychological clocks provides an integrative contribution to healthy and advanced aging. At the molecular level, genome, 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 chirality, 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 related to irreversible PTMs SP has been associated with the nontrivial interplay between somatic (molecular aging) and mental (psychological aging) 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 underappreciated hallmark of aging. We provide the experimental arguments in support of the racemization theory of aging.

scholarly journals Controlling biomolecular condensates via chemical reactions

2021 ◽  
Vol 18 (179) ◽  
pp. 20210255
Author(s):  
Jan Kirschbaum ◽  
David Zwicker
Keyword(s):  
Phase Separation ◽  
Chemical Reactions ◽  
Cell Signalling ◽  
State Theory ◽  
External Energy ◽  
Post Translational Modifications ◽  
Cellular Processes ◽  
Droplet Sizes ◽  
Fast Control ◽  
Non Equilibrium

Biomolecular condensates are small droplets forming spontaneously in biological cells through phase separation. They play a role in many cellular processes, but it is unclear how cells control them. Cellular regulation often relies on post-translational modifications of proteins. For biomolecular condensates, such chemical modifications could alter the molecular interaction of key condensate components. Here, we test this idea using a theoretical model based on non-equilibrium thermodynamics. In particular, we describe the chemical reactions using transition-state theory, which accounts for the non-ideality of phase separation. We identify that fast control, as in cell signalling, is only possible when external energy input drives the reaction out of equilibrium. If this reaction differs inside and outside the droplet, it is even possible to control droplet sizes. Such an imbalance in the reaction could be created by enzymes localizing to the droplet. Since this situation is typical inside cells, we speculate that our proposed mechanism is used to stabilize multiple droplets with independently controlled size and count. Our model provides a novel and thermodynamically consistent framework for describing droplets subject to non-equilibrium chemical reactions.

scholarly journals Spontaneous Determinants of Protein Aging Mini Review

2021 ◽  
Author(s):  
Victor Vasilyevich Dyakin ◽  
Vladimir Nikolaevich Uversky
Keyword(s):  
Equilibrium State ◽  
Protein Misfolding ◽  
Post Translational Modifications ◽  
Molecular Chirality ◽  
Protein Aging ◽  
Living Organisms ◽  
Essential Contribution ◽  
Biological Chirality ◽  
Enzymatic Glycosylation ◽  
Non Equilibrium

The universal chirality is the commonly accepted view of nature. Biological chirality is the distinct part of the more general phenomena. Following this view, all living organisms are characterized by the non-equilibrium state of their molecular constituents. From the thermodynamic perspective, the non-equilibrium state of biomolecular ensemble holds inevitable consequences being the substrate of spontaneous reactions directed to equilibrium (not associated with life) state. At the protein level, spontaneous biological reactions represent the natural part of proteins' post-translational modifications (PTMs). The essential contribution to the origin and maintenance of the non-equilibrium state belongs to prevalent bio-molecular chirality. Correspondently, spontaneous PTMs such as racemization and glycation, working against life-supporting prevalent chirality, are known as the significant determinants of protein misfolding, dysfunctions, and aggregation. Accumulation of aberrant protein during life-span allows consideration of time-dependent spontaneous racemization and glycation as protein aging. Spontaneous PTMs of proteins is occurring in the interaction with other forms of enzymatic and non-enzymatic PTMs. In this review, we are considering the contribution of spontaneous racemization and non-enzymatic glycosylation to protein aging.

scholarly journals Novel Roles for the Sirtuin Deacylase SIRT5 in Normal Physiology and in Cancer

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 741-741
Author(s):  
David Lombard
Keyword(s):  
Mitochondrial Matrix ◽  
Genomic Integrity ◽  
Biological Functions ◽  
Protein Targets ◽  
Post Translational Modifications ◽  
Catalytic Activities ◽  
Cellular Processes ◽  
Specific Cancer ◽  
Cancer Types ◽  
Chromatin Biology

Abstract Sirtuins are NAD+-dependent deacylases that regulate diverse cellular processes such as metabolic homeostasis and genomic integrity. Mammals possess seven sirtuin family members, SIRT1-SIRT7, that display diverse subcellular localization patterns, catalytic activities, protein targets, and biological functions. Three sirtuins, SIRT3, SIRT4, and SIRT5, are primarily located in the mitochondrial matrix. SIRT5 is a very inefficient deacetylase, instead removing negatively charged post-translational modifications (succinyl, glutaryl, and malonyl groups) from lysines of its target proteins, in mitochondria and throughout the cell. SIRT5 plays only modest known roles in normal physiology, with its major functions occurring in the heart under stress conditions. In contrast, in specific cancer types, including melanoma, we have identified a major pro-survival role for SIRT5. We have traced this function of SIRT5 to novel roles for this protein in regulating chromatin biology. New insights into mechanisms of SIRT5 action in cancer, and in normal myocardium, will be discussed.

scholarly journals TFEB Signalling-Related MicroRNAs and Autophagy

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 985
Author(s):  
Davide Corà ◽  
Federico Bussolino ◽  
Gabriella Doronzo
Keyword(s):  
Transcriptional Regulation ◽  
Stress Factors ◽  
Cellular Functions ◽  
Post Translational Modifications ◽  
Cellular Processes ◽  
Factor Deficiency ◽  
Transcription Factor Eb ◽  
Important Regulator ◽  
Response To Stress ◽  
Post Transcriptional Regulation

The oncogenic Transcription Factor EB (TFEB), a member of MITF-TFE family, is known to be the most important regulator of the transcription of genes responsible for the control of lysosomal biogenesis and functions, autophagy, and vesicles flux. TFEB activation occurs in response to stress factors such as nutrient and growth factor deficiency, hypoxia, lysosomal stress, and mitochondrial damage. To reach the final functional status, TFEB is regulated in multimodal ways, including transcriptional rate, post-transcriptional regulation, and post-translational modifications. Post-transcriptional regulation is in part mediated by miRNAs. miRNAs have been linked to many cellular processes involved both in physiology and pathology, such as cell migration, proliferation, differentiation, and apoptosis. miRNAs also play a significant role in autophagy, which exerts a crucial role in cell behaviour during stress or survival responses. In particular, several miRNAs directly recognise TFEB transcript or indirectly regulate its function by targeting accessory molecules or enzymes involved in its post-translational modifications. Moreover, the transcriptional programs triggered by TFEB may be influenced by the miRNA-mediated regulation of TFEB targets. Finally, recent important studies indicate that the transcription of many miRNAs is regulated by TFEB itself. In this review, we describe the interplay between miRNAs with TFEB and focus on how these types of crosstalk affect TFEB activation and cellular functions.

Thermodynamic and Kinetic Calculation of Non-Equilibrium Microstructure Design of TRIP Steel

2014 ◽  
Vol 783-786 ◽  
pp. 766-770
Author(s):  
Yan Lin He ◽  
Na Qiong Zhu ◽  
Wei Sen Zheng ◽  
Xiao Gang Lu ◽  
Lin Li
Keyword(s):  
Trip Steel ◽  
Equilibrium Phase ◽  
Microstructure Design ◽  
Kinetic Calculation ◽  
Software Comparison ◽  
Thermo Calc Software ◽  
Curve Determination ◽  
Equilibrium Microstructure ◽  
The Relationship ◽  
Non Equilibrium

The non-equilibrium microstructure of Fe-C-Mn-Si TRIP steel is designed bythermodynamic and kinetic calculation. The upper limit of bainitic transformation temperature iscalculated and compared to that characterized by CCT curve determination. s M temperature isdetermined based on thermodynamics of martensitic transformation and sublattice model. Thecalculation is conducted via TQ6-patch in Thermo-Calc software. Comparison between thecalculations and experiments reveals the relationship between non-equilibrium phase compositionand heat treatment parameters which can be utilized to achieve the elaborate design of alloy and heattreatment for super TRIP steel.

Heat Transfer Coefficient in Rapid Solidification of a Liquid Layer on a Substrate

2000 ◽  
Vol 122 (4) ◽  
pp. 792-800 ◽  
Author(s):  
P. S. Wei ◽  
F. B. Yeh
Keyword(s):  
Heat Transfer ◽  
Heat Transfer Coefficient ◽  
Transfer Coefficient ◽  
Biot Number ◽  
Equilibrium Phase ◽  
Density Ratio ◽  
Solid Substrate ◽  
Time Dependent ◽  
Bottom Surface ◽  
Melting Front

The heat transfer coefficient at the bottom surface of a splat rapidly solidified on a cold substrate is self-consistently and quantitatively investigated. Provided that the boundary condition at the bottom surface of the splat is specified by introducing the obtained heat transfer coefficient, solutions of the splat can be conveniently obtained without solving the substrate. In this work, the solidification front in the splat is governed by nonequilibrium kinetics while the melting front in the substrate undergoes equilibrium phase change. By solving one-dimensional unsteady heat conduction equations and accounting for distinct properties between phases and splat and substrate, the results show that the time-dependent heat transfer coefficient or Biot number can be divided into five regimes: liquid splat-solid substrate, liquid splat-liquid substrate, nucleation of splat, solid splat-solid substrate, and solid splat-liquid substrate. The Biot number at the bottom surface of the splat during liquid splat cooling increases and nucleation time decreases with increasing contact Biot number, density ratio, and solid conductivity of the substrate, and decreasing specific heat ratio. Decreases in melting temperature and liquid conductivity of the substrate and increase in latent heat ratio further decrease the Biot number at the bottom surface of the splat after the substrate becomes molten. Time-dependent Biot number at the bottom surface of the splat is obtained from a scale analysis. [S0022-1481(00)01004-5]

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