At Longevity Horizon (Online ISSN: 3088-4063) , we bring together the brightest minds from diverse scientific disciplines to contribute to the development of transformative technologies that are poised to shape the future of our world. By uniting experts, researchers, and innovators, we create a dynamic environment where groundbreaking ideas and solutions can flourish. Our mission is to foster collaboration among the world's leading thinkers, making revolutionary scientific discoveries and cutting-edge technologies accessible to the global community. We are dedicated to advancing research that not only has the power to transform individual lives but also to build a more sustainable and thriving future for generations to come. Through our platform, we offer a space for high-quality, peer-reviewed scientific articles that inspire innovation and drive progress. These contributions are paving the way for a future where concepts such as boundless living space, optimal health, food security, and the possibility of eternal youth are no longer distant aspirations, but tangible realities. This is an open access journal, which means that all content is freely available without charge to the user or his/her institution. Users are allowed to read, download, copy, distribute, print, search, or link to the full texts of the articles, or use them for any other lawful purpose, without asking prior permission from the publisher or the author. This is in accordance with the BOAI definition of open access.
Articles published in Longevity Horizon fall under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0). This means authors retain their copyright while granting the journal the right to be the first publisher. Readers are permitted to share and distribute the work as long as proper credit is given. However, the content may not be altered, modified, or used for commercial purposes.
Lake Aquaculture for Catastrophic Food Security
Section: Technology and Innovations Keywords: Food Security, Protein Security, Catastrophe Resilience, Lake Aquaculture, Sustainable Aquaculture, Disaster Preparedness, Polyculture, Resource Efficiency, Climate Adaptation The intensifying frequency of climate disasters, geopolitical conflicts, and pandemics exposes critical vulnerabilities in globalized, input-intensive food systems. Traditional protein sources—terrestrial livestock, crops, and marine fisheries—are highly susceptible to collapse under such catastrophic scenarios due to their dependencies on complex supply chains, external inputs, and stable climatic conditions. This article posits that lake-based aquaculture represents a strategically undervalued yet indispensable component of a resilient food security framework. We argue that the inherent characteristics of lacustrine systems—including superior feed conversion ratios, the utilization of natural trophic pathways, and a static "live storage" production model—confer a unique capacity to function autonomously during prolonged infrastructural and logistical breakdowns. The analysis delineates criteria for selecting resilient fish species, advocates for extensive polyculture management models, and outlines strategies for mitigating risks related to disease, genetic resource security, and ecological degradation. Furthermore, a strategic roadmap is proposed for integrating this approach into national policy, emphasizing legislative action, targeted research, economic incentives, and specialized education. The conclusion asserts that proactive investment in developing lake aquaculture as a decentralized protein reserve is a critical imperative for enhancing national food sovereignty and long-term survivability in an era of escalating systemic risks.
Copyright (c) 2025 Jaba Tkemaladze (Author) https://creativecommons.org/licenses/by-nc-sa/4.0
Section: Technology and Innovations Categories: Cybernetics, Biology, Mathematics Keywords: Bayesian Inference, Stream Processing, Chronotropic Frequencies, Artificial Life, Predictive Coding, Memory Efficiency, Adaptive Systems, Bio-Inspired Computing, Probability Updating This article presents the Ze artificial life system, a novel bio-inspired architecture for predictive processing in infinite data streams under severe memory constraints. The system implements Bayesian probability updating through a mechanism of dynamic chronotropic frequency analysis, demonstrating remarkable computational efficiency and biological plausibility. Unlike traditional approaches such as LSTM networks and Markov models, Ze processes information through parallel beginning and inverse processors, enabling complementary pattern discovery while maintaining sublinear memory complexity. The core algorithm exhibits distinctive probability dynamics characterized by an initial match probability of 0.5 with exponential decay to 0.00001 as counter diversity increases, achieving 78-92% prediction accuracy for stable data flows. Experimental results using synthetic datasets (1,048,576 binary sequences) confirm 37-42% operational savings compared to conventional methods, rapid adaptation to changing stream characteristics within 2-3 seconds, and robust noise tolerance up to 15% input distortion. The Go implementation processes 1.2 million operations per second with 850 nanosecond latency while maintaining memory usage of 12.8 bytes per counter. The system's architecture shows strong neurobiological correlations with predictive coding principles and synaptic plasticity mechanisms, providing both a practical solution for resource-constrained environments and a computational model of Bayesian inference in neural systems. Future development pathways include extension to non-binary data streams, integration with hierarchical Bayesian models, and hardware acceleration through memristor-based implementations.
Concept of Death Awareness as an Existential Regulator in the Age of Biological Immortality
Section: Opinion and Commentary Categories: Biology, Medicine, Physiology, History, Politology, Ecology Keywords: Thanatology, Existential Psychology, Biological Immortality, Senescence, Meaning of Life, Mortality Salience, Terror Management Theory, Identity Crisis, Self-Transcendence The rapid advancement of biogerontology, particularly through interventions like senolytic therapies and stem cell rejuvenation, is transforming the prospect of radical life extension and even biological immortality from science fiction into a plausible future scenario. This impending paradigm shift necessitates a profound re-examination of existential psychology, which has traditionally posited awareness of mortality as the fundamental source of life's meaning, motivation, and authenticity. This article argues that the psychological phenomenon of death awareness would not simply vanish with the elimination of biological finitude. Instead, it would undergo a critical functional transformation. It proposes the concept of an "existential alarm clock," a reconstituted internal mechanism that shifts from serving as a chronological limit to acting as a qualitative regulator of existence. In a state of immortality, this alarm would awaken the individual from the unique perils of an endless lifespan: existential apathy, identity stagnation, and the "bad infinity" of undifferentiated time. The article analyzes the mechanisms of this alarm—triggering identity crises, combating profound boredom, and stimulating self-transcendence—and explores its vast social, cultural, and ethical implications. It concludes that, paradoxically, a continued dialogue with the concept of death remains a crucial condition for a meaningful and authentic life, even in the context of biological immortality.
Induction of de novo centriole biogenesis in planarian stem cells
Section: Research Article Categories: Biology, Medicine, Physiology Keywords: Centriole, De Novo Biogenesis, Planarian, Neoblast, Regeneration, Ciliogenesis, Basal Body, PLK4, SAS-6 The centriole is a fundamental organelle templating cilia formation and ensuring genomic stability. While most cells assemble centrioles using a pre-existing mother as a template, the de novo pathway allows for assembly in their absence. However, the physiological role and regulation of de novo biogenesis in vivo remain poorly understood. The planarian Schmidtea mediterranea, with its abundant somatic stem cells (neoblasts) and dependence on a massive ciliated epithelium for locomotion, presents a unique model to address this gap. We demonstrate that quiescent neoblasts are acentriolar, lacking the templates for canonical duplication. Upon tissue injury, neoblasts are activated and initiate a programmed de novo centriole biogenesis pathway. Super-resolution microscopy and transmission electron microscopy reveal the formation of cytoplasmic procentriolar foci and mature centrioles, independent of any parental structure. Crucially, genetic ablation of Sas-6 or pharmacological inhibition of PLK4—interventions that effectively block the canonical pathway—fail to prevent the formation of new centrioles and functional basal bodies in the regenerating ciliated epithelium. This work provides the first in vivo evidence in a whole organism for an induced de novo centriole biogenesis pathway in adult somatic stem cells. We propose this pathway is a key evolutionary adaptation, enabling rapid, large-scale ciliogenesis essential for planarian regeneration, and represents a distinct, genetically regulated program separable from canonical duplication.
Copyright (c) 2025 Jaba Tkemaladze, Gabro Gakely (Author) https://creativecommons.org/licenses/by-nc-sa/4.0
The Tkemaladze Method maps cell lineage with mutant mitochondrial transfer
Section: Research Article Keywords: Cell Lineage Tracing, Mitochondrial DNA, Mitochondrial Transfer, Heteroplasmy, Developmental Biology, Progenitor Cells, Chimeric Model, Cytogenealogical Map, Regenerative Medicine The comprehensive mapping of cellular lineages from the zygote to a fully formed organism remains a fundamental and unresolved challenge in developmental biology. While modern single-cell technologies offer snapshots of cellular heterogeneity, they lack the inherent, permanent markers required to trace progeny through the complex events of asymmetric division and migration over time. This work introduces the Tkemaladze Method, a novel lineage-tracing approach that utilizes mutant mitochondrial DNA (mtDNA) as a stable, inheritable genetic label. The method involves the isolation of mitochondria from cytoplasts harboring known pathogenic mtDNA mutations and their microinjection into murine embryonic stem cells (mESCs). We confirmed successful transfer and functional integration via fluorescence microscopy and quantitative PCR. These labeled progenitor cells were used to generate chimeric embryos, where we demonstrated stable heteroplasmy and faithful inheritance of the mutant mtDNA in clonal progeny throughout development. Using fluorescent reporters, we visualized the fate of individual progenitors, enabling the quantitative construction of a detailed cytogenealogical map across tissues like the central nervous system, liver, and myocardium. A key finding was the tissue-specific segregation of mitochondrial tags, revealing selective pressure in high-energy-demand tissues. The Tkemaladze Method thus provides an unprecedented, powerful tool for fundamental developmental biology, disease modeling, and tracking the fate of transplanted cells in regenerative medicine.
Section: Opinion and Commentary Categories: Biology, Medicine, Physiology, History, Politology, Ecology, Mathematics Keywords: Lifespan Decline, Biogerontology, Life-History Theory, Genetic Bottleneck, Postdiluvian Adaptation, Biblical Longevity, Somatic Maintenance, Reproductive Trade-Off, Divine Action The dramatic decline in human lifespan described in the biblical genealogies of Genesis 5 and 11 presents a unique intersection of theological narrative and biological inquiry. This paper proposes a multidisciplinary theory to explain this phenomenon, integrating textual analysis with principles from biogerontology and population genetics. We argue that the Genesis Flood narrative represents a catastrophic event that triggered a fundamental shift in human life-history strategy. Statistical analysis of the biblical data reveals a synchronized decline in total lifespan, age at sexual maturity, and reproductive window—a triad consistent with an adaptive transition from a slow to a fast life-history strategy in response to postdiluvian environmental harshness and a genetic bottleneck. This model explains the decline as a trade-off favoring rapid reproduction over somatic maintenance. The case of Job’s divinely granted 140 years is analyzed not as a reversion to antediluvian norms, but as a supernatural blessing within the new biological paradigm, affirming divine sovereignty over natural law. The study concludes that the biblical account, while theological in purpose, exhibits an internal consistency with modern biological principles, offering a coherent framework for understanding this ancient mystery.
Production of Functional Gametes from Somatic Cells of the Planarian Schmidtea Mediterranea Via in Vitro Gametogenesis
Section: Research Article Categories: Biology, Chemistry, Medicine, Physiology Keywords: In Vitro Gametogenesis, IVG, Planarian, Schmidtea Mediterranea, Direct Reprogramming, Germ Cell, Transdifferentiation, Somatic Cell, Reprogramming This study establishes a novel and robust protocol for the direct reprogramming of differentiated somatic cells into functional gamete precursors in the planarian Schmidtea mediterranea, bypassing the need for a pluripotent intermediate state. Through an optimized two-phase in vitro gametogenesis (IVG) protocol involving transient low-dose Yamanaka factor exposure followed by a defined germline-commitment cocktail, we successfully redirected cell fate. Molecular analyses confirmed a stepwise transcriptional and epigenetic reprogramming towards a germline identity, marked by the activation of conserved markers (vasa, nanos, sycp1/3) and global DNA demethylation. While in vitro-derived cells (gametocytes) displayed characteristic oocyte-like and spermatid-like morphologies and ultrastructures, full terminal maturation required in vivo transplantation. Crucially, these IVG-derived gametocytes demonstrated full functionality: upon injection into sterilized recipients, they migrated to gonads, completed maturation, and produced viable, genetically donor-derived offspring. This work provides a powerful platform for studying germ cell development and represents a significant proof-of-concept for somatic cell-to-gamete conversion.
Copyright (c) 2025 Jaba Tkemaladze, Gabro Gakely, Laura Gegelia, Iason Papadopulo, Alexander Taktakidze, Nino Metreveli, Natia Berozashvili, Natalia Bondarenko, Ucha Maglakelidze (Author) https://creativecommons.org/licenses/by-nc-sa/4.0
Unlocking the Voynich Cipher via the New Algorithmic Coding Hypothesis
Section: Opinion and Commentary Categories: Cybernetics, Linguistics, Mathematics Keywords: Voynich Manuscript, Cryptography, Data Compression, LZ77, Huffman Coding, Computational Linguistics, Algorithmic Decryption, Entropy Analysis The Voynich Manuscript (VM) remains one of history's most perplexing cryptographic and linguistic puzzles (Landini & Foti, 2020). This paper introduces a novel hypothesis: that the VM's text is not a direct encoding of a natural language but represents a compressed data stream utilizing principles analogous to modern LZ77 compression and Huffman coding (Huffman, 1952; Ziv & Lempel, 1977). We propose that the manuscript's unusual statistical properties, including its low redundancy and specific word structure, are artifacts of a sophisticated encoding process rather than features of an unknown language (Montemurro & Zanette, 2013; Reddy & Knight, 2011). To evaluate this, we developed a computational framework that treats VM transliterations as a encoded bitstream. This framework systematically tests decompression parameters, using Shannon entropy as a primary fitness metric to identify outputs resembling natural language (Shannon, 1948; Cover & Thomas, 2006). While a complete decipherment is not yet achieved, this methodology provides a new, rigorous, and reproducible computational approach to VM analysis, moving beyond traditional linguistic correlation (Hauer & Kondrak, 2011). The framework's architecture and initial proof-of-concept results are presented, outlining a clear pathway for future research with a fully digitized VM corpus.
Why do planarian cells without centrioles divide and cells with centrioles do not divide?
Section: Reviews and Perspectives Categories: Biology, Medicine, Physiology Keywords: planarian, neoblast, centriole, acentrosomal spindle assembly, regeneration, stem cell, differentiation, chromosomal instability, asymmetric cell division Planarians present a unique cellular paradox: their proliferative stem cells (neoblasts) completely lack centrioles, while their post-mitotic, differentiated cells possess them. This review investigates the mechanisms and biological significance of this inverse correlation. We synthesize evidence demonstrating that neoblasts employ a robust, evolutionarily conserved acentrosomal pathway for spindle assembly, reliant on chromatin-mediated nucleation via RanGTP and motor protein-driven self-organization. This adaptation potentially confers advantages including enforced asymmetric division, metabolic economy, and a significantly reduced risk of centrosome amplification-driven genomic instability, which may underpin the planarians' extensive regenerative capabilities and resistance to tumors. Conversely, the quiescence of centriole-bearing somatic cells is not caused by the organelles themselves but is a consequence of terminal differentiation. These cells epigenetically silence the cell cycle machinery and repurpose centrioles as basal bodies for ciliogenesis. The presence of centrioles is thus a marker, not a driver, of the differentiated state. This system represents a profound uncoupling of the mitotic apparatus from the centriole, offering novel insights into stem cell biology, alternative modes of cell division, and providing conceptual frameworks for regenerative medicine and cancer research.
A Novel Integrated Bioprocessing Strategy for the Manufacturing of Shelf-Stable, Nutritionally Upgraded Activated Wheat: Development of a Comprehensive Protocol, In-Depth Nutritional Characterization, and Evaluation of Biofunctional Properties
Section: Research Article Categories: Biology, Chemistry, Medicine, Physiology, Ecology Keywords: activated wheat, grain sprouting, bioreactor technology, phytic acid reduction, nutrient bioavailability, vacuum-assisted drying, functional food ingredients, shelf-life stability, nutritional fortification Background: Wheat, a cornerstone of global nutrition, possesses inherent nutritional constraints primarily due to the presence of phytic acid, which significantly impedes mineral bioavailability. The process of sprouting has been identified as a promising biological strategy to mitigate these limitations and enhance the nutrient profile. However, a major industrial challenge remains: the pronounced perishability and microbial instability of sprouted grains, which limits their practical application in food systems. Objective: The principal aim of this investigation was to conceive, engineer, and rigorously validate an innovative and scalable biotechnological procedure for the generation of shelf-stable activated wheat. This protocol adheres to stringent technical criteria, including the avoidance of aerial agitation, the implementation of in-vessel dehydration, and the exclusion of convective heat transfer mechanisms. Methods: The methodology centered on the design and operational characterization of a Multi-Function Bioreactor (MFB) system. A comparative examination was executed, pitting the novel protocol against two control processes: traditional laboratory-scale sprouting techniques and historical Georgian artisanal practices. A exhaustive analytical framework was employed, encompassing detailed nutritional assessment (targeting phytic acid, essential vitamins, and macro- and micro-minerals) and comprehensive biochemical evaluation (focusing on antioxidant potential and protein profile modifications). Key Results: The implemented protocol yielded a highly successful reduction of phytic acid content, exceeding 60%. Furthermore, it facilitated a substantial augmentation in the concentrations of B-complex vitamins, notably a 30% increase in Thiamine (B1), a 25% rise in Riboflavin (B2), and a 50% enhancement in Folate levels. The antioxidant capacity, as quantified by DPPH radical scavenging assays, reached an impressive 89%. Critically, the final product achieved a shelf-stable format, demonstrating no significant nutritional degradation over a period exceeding 12 months. Conclusion: The innovative methodology described herein effectively translates a traditional food processing concept into a sophisticated, reproducible, and industrially viable biotechnological operation. The resultant product is a premium-grade, shelf-stable functional food ingredient, whose enhanced nutritional credentials have been thoroughly validated through empirical analysis.
The Tkemaladze Method: A Modernized Caucasian Technology for the Production of Shelf-Stable Activated Wheat with Enhanced Nutritional Properties
Section: Technology and Innovations Categories: Biology, Chemistry, Medicine, Physiology, Ecology Keywords: activated wheat, sprouting technology, phytic acid reduction, low-temperature drying, mineral bioavailability, functional ingredient, shelf-stable, food standardization This paper describes an advanced technological protocol for the production of activated wheat, developed by Tkemaladze et al. and based on traditional Caucasian sprouting practices. The method addresses the critical limitation of traditional sprouted wheat—its high perishability—through the introduction of precise control over activation parameters and a novel low-temperature drying stage. The resulting product is a shelf-stable ingredient (6-12 month stability) with a guaranteed low phytic acid content and preserved high bioactivity. Analytical comparisons confirm that the wheat produced by this method exhibits superior nutritional properties, including higher mineral bioavailability and enhanced antioxidant capacity, compared to samples prepared using standard laboratory sprouting protocols. The Tkemaladze method represents a significant step towards the standardization and commercial scalability of activated wheat for the functional food and nutraceutical industries.
The Stage of Differentiation Into Mature Gametes During Gametogenesis in Vitro
Section: Reviews and Perspectives Keywords: in vitro gametogenesis, stem cells, differentiation, meiosis, reproductive biology In vitro gametogenesis (IVG) stands as a revolutionary breakthrough in reproductive biology, offering the unprecedented capability to generate functional gametes from pluripotent stem cells (PSCs). This comprehensive review systematically consolidates contemporary advancements in the differentiation of PSCs into mature germ cells, with a particular emphasis on the pivotal stages governing this intricate process: the formation of primordial germ cells (PGCs), the execution of meiotic division, and the final maturation of gametes. Special attention is devoted to the molecular mechanisms orchestrating each differentiation phase, including the critical roles of BMP and WNT signaling pathways, as well as transcription factors such as PRDM1 and SOX17. In murine models, IVG technology has yielded remarkable outcomes—functional oocytes and spermatozoa capable of successful fertilization and the production of healthy offspring have been reliably generated. However, when applied to human cells, researchers encounter substantial challenges, including suboptimal differentiation efficiency (ranging from 20-40% for PGCs and plummeting to less than 1% for meiotic entry), epigenetic aberrations, and the inadequacy of current in vitro culture systems. This review meticulously examines these limitations and proposes potential strategies to overcome them, such as the integration of organoid technologies, CRISPR-based screening, and epigenetic modulators. The clinical prospects of IVG encompass the treatment of diverse infertility disorders, preimplantation genetic diagnostics, and the conservation of genetic diversity in endangered species. Particular emphasis is placed on the ethical dimensions of this technology and the urgent necessity for establishing international regulatory standards to govern its clinical application. The review underscores the importance of a multidisciplinary approach, merging insights from cell biology, genetic engineering, and reproductive medicine to propel this promising field forward.
Induction of germline-like cells (PGCLCs)
Section: Reviews and Perspectives Categories: Biology, Chemistry, Medicine Keywords: PGCLCs, primordial germ cells, pluripotent stem cells, epigenetic reprogramming, gametogenesis, infertility, reproductive medicine, germ cell specification, in vitro gametogenesis Investigations into primordial germ cell-like cells (PGCLCs) constitute a rapidly evolving frontier in reproductive biology and regenerative medicine, offering transformative potential for both basic research and clinical applications. These in vitro-derived PGCLCs, generated either from pluripotent stem cells (including embryonic and induced pluripotent stem cells) or through direct somatic cell reprogramming, serve as indispensable models for elucidating the intricate molecular mechanisms governing gametogenesis, large-scale epigenetic reprogramming events, and the pathophysiology underlying various forms of infertility. Seminal advancements in this domain include the establishment of robust differentiation protocols employing critical signaling molecules such as bone morphogenetic proteins (BMPs), WNT pathway agonists, and retinoic acid derivatives, alongside innovative approaches involving direct lineage conversion of somatic cell types. Nevertheless, persistent challenges remain, particularly concerning the incomplete recapitulation of epigenetic reprogramming fidelity and suboptimal differentiation efficiencies observed in human cellular systems compared to murine models. The potential applications of PGCLC technology span diverse areas including but not limited to: novel infertility interventions, precise genetic correction of heritable disorders through advanced gene editing techniques, and groundbreaking conservation strategies for endangered species preservation. Importantly, the ethical and regulatory landscapes surrounding artificial gamete derivation, including ontological status considerations and longitudinal safety assessments for potential offspring, necessitate ongoing multidisciplinary discourse and policy development.
Through In Vitro Gametogenesis — Young Stem Cells
Section: Reviews and Perspectives Categories: Biology, Medicine, Physiology Keywords: gametogenesis, in vitro, stem cells, centrioles, reprogramming, reproduction , rejuvenation In vitro gametogenesis (IVG) represents a groundbreaking technology that opens new horizons in reproductive and regenerative medicine. Recent advancements enable the direct reprogramming of somatic cells into germline cells, bypassing the pluripotency stage, which reduces the risk of genetic abnormalities and accelerates the process. The key stages of IVG include the induction of primordial germ cell-like cells (PGCLCs), differentiation into mature gametes, and the formation of functional germ cells under controlled conditions. The primary signaling pathways involved in this process are BMP, WNT, and retinoic acid, which regulate initiation, proliferation, and meiotic entry. To accurately replicate the gonadal microenvironment, researchers employ 3D cultures, organoid systems, and microfluidic devices. Despite significant progress, the efficiency and quality of in vitro-derived gametes still fall short of their natural counterparts. Future developments in this technology hinge on optimizing differentiation protocols, leveraging single-cell technologies, integrating genome editing, and establishing international standards. Additionally, IVG holds promise for systemic rejuvenation by replacing aged stem cells with young ones derived from reprogrammed cells. Ethical and regulatory concerns remain pressing, particularly regarding artificial embryo creation and potential social inequalities. IVG has the potential to become a cornerstone technology in treating aging, extending healthy lifespan, addressing age-related diseases, and overcoming infertility.
Section: Research Article Keywords: artificial intelligence, forecast, filtering, updating, data flow, biologically inspired algorithms, energy-efficient computing This article presents an innovative predictive model of the world based on dynamic updating and adaptive filtering of predicates. The system processes elementary units of information - "crumbs" - to build a probabilistic picture of the environment, demonstrating an initial probability of matches of 0.5 and exponential decay to 0.00001 as the number of counters increases. Key mechanisms include: (1) updating significant patterns with PredictIncrement=2, (2) filtering rarely used predicates while maintaining plasticity balance (γ≥0.95), and (3) resource-efficient architecture providing 37-42% computational savings. Experimental results show prediction accuracy of 78-92% for stable flows, adaptation speed of 2-3 seconds, and robustness to 15% noise. A comparative analysis revealed advantages over LSTM networks (3 times less training data) and Markov models (40% higher adaptability). The model exhibits biologically plausible properties, including nonlinear attention distribution and energy efficiency similar to that of the neocortex (40-45%). Application prospects include IoT, cybersecurity and power system management, and further research is aimed at integrating the temporal model and hierarchical organization of patterns.
Mechanisms of Learning Through the Actualization of Discrepancies
Section: Technology and Innovations Categories: Cybernetics, Biology, Physiology, Linguistics, Mathematics Keywords: adaptive systems, model of the world, updating of discrepancies, reality manipulation, memory, forecasting, learning balance Adaptive systems, whether biological or artificial, rely on internal models to interact with their environment. This study investigates a learning mechanism driven by discrepancies between predictions and reality. A two-level computational system is analyzed: (1) passive pattern memorization and (2) active model correction. Key adaptive elements include fixed input-processing blocks (analogous to sensory channels), dynamic weight adjustments (memory-like), and a balance between model updating (learning acceleration) and stabilization. Memory plays a central role, with statistical data (*_tendency.csv) forming predictive foundations and an optimization algorithm refining them. Healthy adaptation requires equilibrium between plasticity and resilience. The framework demonstrates broad applicability, spanning AI and cognitive science. Unlike traditional views of memory as mere recall, this model emphasizes its dual role in both memorization and world-model formation, achieved through integrated memory functions. The results highlight memory’s potential as a core adaptive mechanism, bridging machine and biological learning. This approach advances AI development while offering novel insights into natural cognition, underscoring the parallels between artificial and biological adaptive systems.
Memorizing an Infinite Stream of Information in a Limited Memory Space: The Ze Method of a Plastic Counter of Chronotropic Number Frequencies
Section: Technology and Innovations Categories: Physics, Cybernetics, Mathematics Keywords: streaming data, chronotropic frequencies, flexible counters, adaptive algorithms, frequency analysis, dynamic normalization, real-time processing This paper presents an innovative method for creating a flexible chronotropic frequency counter for processing endless data streams. The method solves the key problem of limited memory in modern information systems, offering an effective solution for frequency analysis of dynamic flows. The approach is based on a combination of adaptive counters, temporal smoothing and dynamic normalization, which provides high accuracy (±2%) with sublogarithmic memory usage. Experiments on synthetic data (1,048,576 binary sequences) confirmed the advantages of the method: 18.7% higher accuracy compared to the sliding window algorithm and stability when reducing memory to 0.01% of the original volume. The method demonstrates a linear dependence of processing time on the volume of data (R²=0.98) and rapid adaptation to changes in the flow (12.4±3.1 iterations). The practical significance of the research lies in its application to create real artificial intelligence with the ability to independently adapt to changing environmental conditions, as well as analyze network traffic, process biometric data and create adaptive recommendation systems.
Ontogenetic Permanence of Non-Renewable Biomechanical Configurations in Homo Sapiens Anatomy
Section: Editorial Categories: Biology, Medicine, Physiology Keywords: aging, entropy, irreparable structures, centrioles, mitochondria, crystallins, neuronal DNA Aging in biological organisms is intricately linked to the accumulation of damage in long-lived irreparable structures, which remain unchanged throughout life. These structures include lens proteins (crystallins), DNA of postmitotic neurons, mitochondria of cardiomyocytes, tooth enamel, and centrioles of stem cells. Formed in the early stages of ontogenesis, they serve as "entropy accumulators"—a thermodynamic measure of molecular disorder. The impossibility of their replacement is dictated by evolutionary compromises: for instance, the stability of centrioles is crucial for the asymmetric division of stem cells, yet their selective inheritance results in the transfer of damage to progeny, thereby accelerating tissue aging. The accumulation of oxidized proteins, DNA mutations, and dysfunctional organelles disrupts homeostasis, triggering neurodegeneration, cataracts, and heart failure. This article examines the mechanisms underlying the damage to these structures, their role in age-related pathologies, and promising therapeutic strategies, including senolytics, CRISPR correction, and biomimetic materials. Special emphasis is placed on centrioles as key regulators of cellular entropy: while their stability supports tissue regeneration, defect accumulation leads to gene expression disruption and contributes to oncogenesis. Understanding the balance between longevity and vulnerability in irreparable structures opens new avenues for combating aging through targeted entropy management.
Different Molecular Pathways of Cardiovascular Aging
Section: Reviews and Perspectives Categories: Biology, Medicine, Physiology Keywords: aging heart, cardiovascular aging, senescence, molecular pathways Aging is an inevitable process that affects every living organism. It is a bodys response to a variety of stressors and is connected to many chronic diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), cardiovascular disease… The aim of this review was to further comprehend the mechanisms of aging process and its effect on cardiovascular system. For collecting sufficient data, different scientific databases were used. In the end, there is no exact conclusion of exactly what causes aging, instead we have different theories of its molecular origins such as: oxidative stress, general wear-and-tear and genetic instability, mitochondrial genome damage, telomere shortening, genetic aging programs… Aging process, especially oxidative stress plays a major role in the pathophysiology of cardiomyocyte senescence. Biological compounds like MicroRNAs, SIR1 gene, NF-κB and IL-4, P66Shc, AMP-activated kinase (AMPK) has also been shown to participate or conduct molecular pathways that take part in aging process as well.
Copyright (c) 2025 mariam beriashvili (Author) https://creativecommons.org/licenses/by-nc-sa/4.0
Anti-Blastomic Substances in the Plasma of Schizophrenia Patients: A Dual Role of Complement C4 in Synaptic Pruning and Tumor Suppression
Section: Research Article Categories: Biology, Chemistry, Medicine, Physiology Keywords: schizophrenia spectrum disorders, C4A genetic variants, synaptic refinement processes, complement cascade activation, anti-tumor immunity mechanisms, precision medicine strategies, integrative biomedical research Schizophrenia, a multifaceted neuropsychiatric disorder characterized by disruptions in neurodevelopmental trajectories, has been robustly linked to dysregulated synaptic pruning mechanisms and persistent immune system activation. The present study investigates the intricate interplay between the activity of the complement C4 gene—a pivotal regulator of synaptic pruning—and the incidence of malignant neoplasms in individuals diagnosed with schizophrenia. Our methodological approach integrated three primary investigative arms: (1) large-scale epidemiological meta-analyses encompassing a cohort of 15,000 patients, (2) in vitro experiments utilizing serum from schizophrenia patients to assess its impact on cancer cell proliferation, and (3) genetic profiling to quantify C4 expression patterns. Key findings revealed: (1) a statistically significant 20% reduction in cancer incidence among schizophrenia patients relative to the general population (p<0.01), (2) potent suppression of neoplastic cell growth (up to 40%) following exposure to patient-derived serum, and (3) a strong positive correlation between C4A allelic variants and anti-proliferative efficacy (r=0.58, p<0.001). We postulate that C4 hyperactivation in schizophrenia exerts dual biological effects: exacerbating synaptic elimination through microglial-mediated pruning while concurrently enhancing tumor surveillance via complement-dependent immunomodulation. These findings illuminate the pleiotropic nature of complement proteins in both neurodevelopmental pathology and oncological protection, offering novel therapeutic avenues for cancer management and schizophrenia pathobiology.
Copyright (c) 2025 Jaba Tkemaladze (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
Exploring the Chemical Composition, Therapeutic Properties, and Innovative Delivery Methods of Melissa officinalis
Section: Reviews and Perspectives Melissa officinalis L., colloquially termed lemon balm, stands as a preeminent medicinal herb lauded for its intricate phytochemical matrix and diverse therapeutic applications. This comprehensive review synthesizes contemporary research on its chemical constituents, pharmacological efficacy, and advancements in nanotechnology-driven delivery platforms. The plant’s bioactive arsenal—encompassing flavonoids, terpenoids, phenolic acids, and volatile oils—exerts antioxidant, antimicrobial, anti-inflammatory, and neuroprotective effects. Innovations in drug delivery, such as nanoemulsions, lipid nanoparticles, and polymeric films, aim to enhance bioavailability and therapeutic precision. By integrating multidisciplinary insights, this article underscores the imperative for continued exploration of Melissa officinalis in modern pharmacotherapy.
Copyright (c) 2025 Marima Kipshidze (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
Aging Model Based on Drosophila melanogaster: Mechanisms and Perspectives
Section: Reviews and Perspectives Keywords: aging, drosophila melanogaster, dietary restrictions, signaling pathways, metabolism, epigenetics, model Aging is a multifaceted biological process characterized by a gradual decline in physiological functions, ultimately resulting in reduced reproductive capacity and eventual death of the organism. For over a century, Drosophila melanogaster, the common fruit fly, has served as a pivotal model for investigating the underlying mechanisms of aging, owing to its relatively short lifespan, ease of genetic manipulation, and high degree of conservation of molecular pathways with higher organisms. This article delves into the principal aspects of utilizing Drosophila in aging research, encompassing the influence of dietary restrictions, insulin/IGF-1, mTOR, and AMPK signaling pathways, as well as the roles of various tissues—such as the intestine and muscles—in modulating lifespan. Special emphasis is placed on the interplay between metabolic and epigenetic factors that determine the rate of aging and on the potential applications of these findings in the development of anti-aging therapeutic strategies.
The Centriolar Theory of Differentiation Explains the Biological Meaning of the Centriolar Theory of Organismal Aging
Section: Reviews and Perspectives Categories: Biology, Medicine, Physiology Keywords: centrioles, aging, genomic instability, senescence, oxidative stress, stem cell dysfunction, biogerontology Centrioles, once thought to be simple structural components of the cell, have emerged as critical players in the aging process. This article reviews the existing theories linking centrioles to organismal aging, focusing on their roles in genomic stability, stem cell function, ciliary signaling, oxidative stress, and replicative Hyflick limit. Explored the evidence from model organisms, human studies, and clinical implications, highlighting the potential of centriole-targeted therapies to delay aging and prevent age-related diseases. By integrating findings from cellular biology, genetics, and clinical research, this article provides a comprehensive overview of the current understanding of centrioles in aging and outlines future directions for research and therapeutic development. The Centriolar Theory of Aging of the Organism is presented, which sees the accumulation of old, unrepairable centrioles in the organism as the main cause of the aging phenomenon. The biological meaning of this theory is explained by the Centriolar Theory of Differentiation, which links differentiation with centrioles. Thus, aging of the organism is not a separately programmed process or a separately stochastic process - both of these processes contribute. Aging of the organism is the result of the accumulation of old, unrepairable centrioles (stochastically accumulating defects) by the organism due to the implementation of differentiation programs (in the processes of development and then self-restoration).
Molecular Insights and Radical Longevity from Ancient Elixirs to Mars Colonies
Section: Technology and Innovations Categories: Biology, Medicine, Physiology, History Keywords: aging, longevity, centrioles, stem cells, CRISPR, autophagy, biogerontology Aging is a complex biological process that has intrigued humanity for millennia, shaping cultural beliefs, scientific exploration, and medical advancements. From ancient Egyptian notions of "heart exhaustion" to contemporary models of cellular senescence, the perception of aging has evolved alongside technological progress. This article provides an interdisciplinary analysis of aging, integrating historical, philosophical, and molecular perspectives. It examines key theories, from early humoral concepts to modern insights into genomic instability, mitochondrial dysfunction, and the accumulation of damaged centrioles. Special attention is given to recent breakthroughs in longevity research, including genome editing, senolytics, and stem cell-based rejuvenation strategies. Advances in artificial intelligence and bioinformatics have further accelerated the search for geroprotective interventions, enabling the identification of novel molecular targets. Despite these achievements, aging remains a major risk factor for chronic diseases, necessitating a shift from symptom-based treatments to fundamental interventions aimed at delaying or reversing biological aging. By synthesizing data from diverse fields, this article proposes an integrative framework for addressing aging, emphasizing the need for a systemic approach that combines gerontology, molecular biology, and computational modeling to extend healthspan and lifespan.
Protocol for Transplantation of Healthy Cells Between Adult Drosophila of Different Ages and Sexes
Section: Technology and Innovations Categories: Biology, Chemistry, Medicine Keywords: аllotransplantation, drosophila melanogaster,, sexual dimorphism, pathway, aging, signaling Drosophila melanogaster serves as a powerful and versatile model organism for studying tissue allotransplantation due to its short life cycle, genetic manipulability, and significant homology to mammalian signaling pathways. This protocol outlines a procedure for performing tissue transplants between adult individuals of different ages and sexes. Key steps include dissection of the donor’s midgut tissue, microinjection into the recipient, and tracking engraftment using sex chromosome differences. The protocol demonstrates high short-term survival (over 80%) of host organisms, with transplanted tissues encapsulated by hemocytes. Sexual dimorphism affects transplant outcomes, with females showing stronger immune responses through the Toll pathway, resulting in more frequent rejections, while males exhibit greater tissue tolerance. Age-related factors, including reduced regenerative capacity and oxidative stress in older individuals, impact transplantation success. This methodology also enables modeling of intestinal stem cell regeneration. Despite challenges such as small tissue size and lack of an adaptive immune system, the protocol offers valuable insights into innate immunity, aging, and intercellular interactions, positioning Drosophila as an ideal preclinical model for studying tissue regeneration and immune response.
Centriole Elimination: A Mechanism for Resetting Entropy in the Cell
Section: Reviews and Perspectives Categories: Biology, Medicine, Physiology Keywords: centrioles, elimination, entropy, totipotency, differentiation, aging Centrioles are highly conserved organelles within the eukaryotic domain of life, playing an indispensable role in microtubule organization, cellular differentiation, and the formation of cilia and flagella. However, in the processes of oogenesis and spermatogenesis in certain organisms, centrioles undergo elimination, thereby preventing the transmission of either young or aged centrioles to the zygote, depending on the specific system of asymmetric division. The removal of centrioles in gametes can be interpreted as a mechanism of resetting cellular entropy and restoring totipotency, which is crucial for embryonic development. In somatic cells, centriole elimination is also observed during terminal differentiation, suggesting a potential connection to replicative aging. Research indicates that the programmed removal of centrioles is linked to degradation mechanisms involving microtubule breakdown and the ubiquitin-proteasome system. Centrioles are unique in the cellular architecture as they lack self-repair mechanisms, leading to the continuous accumulation of entropy, thereby contributing to cellular and organismal aging. Consequently, eliminating centrioles where they are no longer needed can be seen as a countermeasure against aging. Furthermore, centriole elimination plays a pivotal role in preventing centrosome-related pathologies, abnormal cell division, and possibly even oncogenesis. Investigating the mechanisms of centriole elimination opens promising avenues in biomedicine, including strategies for tissue rejuvenation and aging control.
Asymmetry in the Inheritance of Centrosomes / Centrioles and Its Consequences
Section: Opinion and Commentary Categories: Biology, Chemistry, Medicine Keywords: centrosome, centrioles, stem cells, asymmetric division, progenitor cells, sibling cells Asymmetric division of stem cells plays a fundamental role in maintaining tissue homeostasis by ensuring a delicate balance between self-renewal and differentiation. Within this process, the centrosome and its components, including centrioles, exhibit both functional and structural asymmetry. The mother and daughter centrioles are inherited in a stereotypical manner, influencing the fate of sibling cells. The mother centriole, possessing a higher microtubule-organizing capacity, often remains in the stem cell, while the daughter centriole is transmitted to the differentiating progeny. This mechanism has been observed in germline stem cells of Drosophila and radial glial cells in mammals. However, in Drosophila neuroblasts, an opposite strategy is maintained: the daughter centriole remains in the stem cell, whereas the mother centriole is passed on to the progenitor cells. These differences may be linked to the regulation of cell fate, aging, and tissue longevity. A deeper understanding of the role of centrioles in these processes could pave the way for new approaches in regenerative medicine and anti-aging therapies.
Differentiation of Somatic Cells in Multicellular Organisms
Section: Reviews and Perspectives Categories: Biology, Medicine, Physiology Keywords: asymmetric cell division, tf, grn, replicative aging, fibroblast cultures, telomeres Multicellular organisms employ intricate gene regulatory networks (GRNs) to orchestrate cell fate decisions, yet the precise regulatory mechanisms that govern transcription factors (TFs) within these networks remain exceptionally complex. A long-standing question in this field pertains to how these intricate interactions synergistically contribute to decision-making processes. To gain a comprehensive understanding of the role of regulatory logic in cell fate determinations, we developed a logical model of GRNs and examined its behavior under two distinct driving forces—one governed by stochastic noise and the other by deterministic signaling. Under noise-driven conditions, we identified a correlation between fate biasing, regulatory logic, and noise profile dynamics. In the signal-driven mode, we established a connection between regulatory logic and the trade-off between accuracy and progression speed, revealing distinct reprogramming trajectories influenced by specific logical motifs. Through differentiation studies, we characterized a unique priming stage that is dependent on regulatory logic, employing decision landscapes for analysis. Finally, we applied our findings to elucidate three biological cases: hematopoiesis, embryogenesis, and transdifferentiation. Orthogonally to classical expression profile analysis, we leveraged noise pattern recognition to construct GRNs corresponding to fate transitions. Our research presents a generalizable framework for downstream investigations of fate determination and offers a practical approach for the taxonomy of cell fate decisions.
Section: Letters to the Editor Keywords: replicative limit, replicative aging, replicometer, fibroblast cultures, telomeres In the mid-20th century, Leonard Hayflick discovered that normal human cells have a limited number of divisions, which became a significant contribution to the study of replicative aging. Together with Paul Moorhead, he demonstrated that the replicative limit of cells is a fundamental biological feature. Their research led to the concept of the replicometer and the idea of telomeres as a mechanism that restricts cell divisions. Alexey Olovnikov proposed a hypothesis explaining the shortening of telomeres during each replication cycle. The discoveries of Hayflick, Olovnikov, and Blackburn laid the foundation for research into replicative immortality, which is of critical importance for understanding replicative aging and cancer. Research has identified the existence of two classes of cells—replicatively mortal and replicatively immortal. To this day, the replicometer remains to be discovered.
Anatomy, Biogenesis, and Role in Cell Biology of Centrioles
Section: Reviews and Perspectives Categories: Biology, Medicine, Physiology Keywords: centrioles, biogenesis, microtubules, cell cycle, cell polarity, maturation Centrioles are essential cellular organelles that play a key role in cell division, cytoskeletal organization, and microtubule dynamics. Their unique structure and ability to self-replicate make centrioles indispensable for the regulation of cellular processes. This article focuses on the anatomy of centrioles, their biogenesis, and their role in cell biology. The first part of the study describes the structural features of centrioles, including the ninefold symmetry that forms the foundation of their morphology. Special attention is given to centriole biogenesis, covering processes such as the initiation of assembly, the establishment of ninefold symmetry, microtubule assembly, and elongation. Mechanisms of temporal regulation, length control, and the formation of the distal end are also discussed. Additionally, the article examines centriole maturation processes and their functional significance in the context of the cell cycle, cell polarity, and intracellular transport. The presented data are based on a review of contemporary studies, including structural models and biochemical mechanisms. This work highlights the importance of centrioles for understanding fundamental cellular biology processes and provides a foundation for further research into their roles in health and disease.