搜索结果：Neurobiology of aging

It is now increasingly realized that the underlying mechanism which governs aging (ageing) is a complex interplay of genetic regulation and damage-accumulation. "Aging as a result of accumulation of 'faults' on cellular and molecular levels", has been proposed in the damage (fault)-accumulation theory. However, this theory fails to explain some aging phenotypes such as fibrosis and premature aging, since terms such as 'damage' and 'fault' are not specified. Therefore we introduce some crucial modifications of this theory and arrive at a novel theory: aging of the body is the result of accumulation of Misrepair of tissue. It emphasizes: a) it is Misrepair, not the original damage, that accumulates and leads to aging; and b) aging can occur at different levels, however aging of the body takes place necessarily on the tissue level, but not requiring the aging of cells/molecules. The Misrepair-accumulation theory introduced in the present paper unifies the understanding of the roles of environmental damage, repair, gene regulation, and multicellular structure in the aging process. This theory gives explanations for the aging phenotypes, premature aging, the difference of longevity in d

Automatically generated software, especially code produced by Large Language Models (LLMs), is increasingly adopted to accelerate development and reduce manual effort. However, little is known about the long-term reliability of such systems under sustained execution. In this paper, we experimentally investigate the phenomenon of software aging in applications generated by LLM-based tools. Using the Bolt platform and standardized prompts from Baxbench, we generated four service-oriented applications and subjected them to 50-hour load tests. Resource usage, response time, and throughput were continuously monitored to detect degradation patterns. The results reveal significant evidence of software aging, including progressive memory growth, increased response time, and performance instability across all applications. Statistical analyzes confirm these trends and highlight variability in the severity of aging according to the type of application. Our findings show the need to consider aging in automatically generated software and provide a foundation for future studies on mitigation strategies and long-term reliability evaluation.

Age spots are the brown spots that develop in the skin but change in color and shape with time. To understand the mechanism of development of age spots, characteristics of age spots are analyzed by Misrepair mechanism, a mechanism introduced in Misrepair-accumulation aging theory. An age spot is pathologically a group of aggregated basal cells, which contain lipofuscin bodies. Accumulation of lipofuscin bodies is a sign of aging of a cell. Characteristics of age spots include: inhomogeneity in distribution, growing flatly before becoming protruding, irregularity on shape, inhomogeneity on the color and on the protruding degree of a spot, and softness of a protruding spot. After analyzing these characteristics, we make a hypothesis on the process of development of an age spot. A. Aging of a tissue is the basis for development of age spots. B. A flat spot results from accumulation of lipofuscin containing cells. When an aged cell remains, this cell can accelerate the aging of its neighbor cells by increasing damage sensitivity and reducing repair efficiency of the local tissue. By a viscous circle, more and more neighbor cells become aged and they form a flat spot, which has an irreg

This paper proposes an original theory of aging of multicellular organisms. The cells of multicellular organisms, in contrast to unicellular organisms, are burdened with a two- part genome: housekeeping and specialized (multicellular), responsible for ontogenesis and terminal differentiation. The two parts of the genome compete for limited adaptive resources thereby interfering with the ability of the house-keeping part of the genome to adequately perform reparative and adaptive functions in post mitotic cells. The necessity to complete the ontgenesis program, leads to increased activity of the multicellular components of the genome. As a result, the allocation of cellular resources to specialized genome con-tinuously increases with time. This leads to a deficit of reparative and adaptive capacity in post mitotic cells. Suggestions for future research focus on identifying groups of genes responsible for regulation of growth rate of specialized genome and suppressing ability of the cell division. A better understanding of the relationship between the two parts of the genome will not only help us to manipulate ontogenesis and aging, but will also improve our understanding of cancer d

Lexical Semantic Change (LSC) is the phenomenon in which the meaning of a word change over time. Most studies on LSC focus on improving the performance of estimating the degree of LSC, however, it is often difficult to interpret how the meaning of a word change. Enhancing the interpretability of LSC is a significant challenge as it could lead to novel insights in this field. To tackle this challenge, we propose a method to map the semantic space of contextualized embeddings of words obtained by a pre-trained language model to a neurobiological feature space. In the neurobiological feature space, each dimension corresponds to a primitive feature of words, and its value represents the intensity of that feature. This enables humans to interpret LSC systematically. When employed for the estimation of the degree of LSC, our method demonstrates superior performance in comparison to the majority of the previous methods. In addition, given the high interpretability of the proposed method, several analyses on LSC are carried out. The results demonstrate that our method not only discovers interesting types of LSC that have been overlooked in previous studies but also effectively searches for

The role of additives such as FEC in extending the calendar life of silicon anodes beyond the cycling benefits is still not fully understood. Herein, the calendar life of high-loading Si (80 wt%) using baseline 1.2 M LiPF6 in EC-EMC electrolyte versus adding 10 wt% FEC is investigated over months. Over 8 days of aging, FEC leads to a 13-fold reduction in irreversible capacity loss in Si-LiFePO4 full cells. Cells without FEC are projected to fall below 80% of their initial capacity within approx. 22 days versus approx. 279 days with FEC. Symmetric Si-Si cells from harvested electrodes show greater increase in interphase resistance without FEC, whereby an increase of 10.81 Ohms is measured for 0 wt% FEC vs. only 3.37 Ohms for 10 wt% FEC over 2 months. Power law modeling of this long-term interphase resistance finds mixed transport-reaction growth behavior in FEC-free cells, suggesting significant dissolution, whereas cells with 10 wt% FEC added display a diffusion-controlled impedance growth behavior, suggesting a robust surface passivation film. Post-mortem FTIR and XPS confirm polycarbonate enrichment of the SEI, which was discovered to predominantly emerge from FEC self-polymeriza

We propose a new theory for aging based on dynamical systems and provide a data-driven computational method to quantify the changes at the cellular level. We use ergodic theory to decompose the dynamics of changes during aging and show that aging is fundamentally a dissipative process within biological systems, akin to dynamical systems where dissipation occurs due to non-conservative forces. To quantify the dissipation dynamics, we employ a transformer-based machine learning algorithm to analyze gene expression data, incorporating age as a token to assess how age-related dissipation is reflected in the embedding space. By evaluating the dynamics of gene and age embeddings, we provide a cellular aging map (CAM) and identify patterns indicative of divergence in gene embedding space, nonlinear transitions, and entropy variations during aging for various tissues and cell types. Our results provide a novel perspective on aging as a dissipative process and introduce a computational framework that enables measuring age-related changes with molecular resolution.

Aging, the process of growing old or maturing, is one of the most widely seen natural phenomena in the world. For the stochastic processes, sometimes the influence of aging can not be ignored. For example, in this paper, by analyzing the functional distribution of the trajectories of aging particles performing anomalous diffusion, we reveal that for the fraction of the occupation time $T_+/t$ of strong aging particles, $\langle (T^+(t)^2)\rangle=\frac{1}{2}t^2$ with coefficient $\frac{1}{2}$, having no relation with the aging time $t_a$ and $α$ and being completely different from the case of weak (none) aging. In fact, we first build the models governing the corresponding functional distributions, i.e., the aging forward and backward Feynman-Kac equations; the above result is one of the applications of the models. Another application of the models is to solve the asymptotic behaviors of the distribution of the first passage time, $g(t_a,t)$. The striking discovery is that for weakly aging systems, $g(t_a,t)\sim t_a^{\fracα{2}}t^{-1-\fracα{2}}$, while for strongly aging systems, $g(t_a,t)$ behaves as $ t_a^{α-1}t^{-α}$.

This chapter demonstrates how computational social science (CSS) tools are extending and expanding research on aging. The depth and context from traditionally qualitative methods such as participant observation, in-depth interviews, and historical documents are increasingly employed alongside scalable data management, computational text analysis, and open-science practices. Machine learning (ML) and natural language processing (NLP), provide resources to aggregate and systematically index large volumes of qualitative data, identify patterns, and maintain clear links to in-depth accounts. Drawing on case studies of projects that examine later life--including examples with original data from the DISCERN study (a team-based ethnography of life with dementia) and secondary analyses of the American Voices Project (nationally representative interview)--the chapter highlights both uses and challenges of bringing CSS tools into more meaningful dialogue with qualitative aging research. The chapter argues such work has potential for (1) streamlining and augmenting existing workflows, (2) scaling up samples and projects, and (3) generating multi-method approaches to address important question

Extrusion-based 3D printing has become one of the most common additive manufacturing methods and is widely used in engineering. This contribution presents the results of flexural creep experiments on 3D printed PLA specimens, focusing on changes in creep behavior due to physical aging. It is shown experimentally that the creep curves obtained on aged specimens are shifted to each other on the logarithmic time scale in a way that the theory of physical aging can explain. The reason for the physical aging of 3D printed thermoplastics is assumed to be the special heat treatment that the polymer undergoes during extrusion. Additionally, results of a long-term flexural creep experiment are shown, demonstrating that non-negligible creep over long periods can be observed even at temperatures well below the glass transition temperature. Such creep effects should be considered for designing components made of 3D printed thermoplastics.

A long term operation of Multi-Strip Multi-Gap Resistive Plate Chambers (MSMGRPC) with gas mixtures based on C2H2F4 and SF6 leads to aging effects, observed as depositions on the surface of the resistive electrodes. Moreover, enhanced depositions and higher noise rates were evidenced around the nylon spacers used for defining the gas gaps between the resistive electrodes. The aging effects are reflected in an increase of the dark current and dark counting rate, with negative impact on the long term performance of the chamber and data volume in a free running readout mode operation. MSMGRPC prototypes designed with a direct gas flow through the gas gaps and minimization of the number of spacers in the active area were developed as mitigation solution. Prototypes with this new design and different granularities were assembled using fishing line as spacers and investigated for aging effects. Although a significant reduction in the dark current and dark counting rate was evidenced, dark counting rate localized around the fishing line spacers remains. In this paper, a new generation of direct flow chambers based on discrete spacers is presented. The results of their aging investigations

Rapid anthropogenic environmental changes, including those due to habitat contamination, degradation, and climate change, have far-reaching effects on biological systems that may outpace animals' adaptive responses (Radchuk et al., 2019). Neurobiological systems mediate interactions between animals and their environments and evolved over millions of years to detect and respond to change. To gain an understanding of the adaptive capacity of nervous systems given and unprecedented pace of environmental change, mechanisms of physiology and behavior at the cellular and biophysical level must be examined. While behavioral changes resulting from anthropogenic activity are becoming increasingly described, identification and examination of the cellular, molecular, and circuit-level processes underlying those changes are profoundly under-explored. Hence, the field of neuroscience lacks predictive frameworks to describe which neurobiology systems may be resilient or vulnerable to rapidly changing ecosystems, or what modes of adaptation are represented in our natural world. In this review, we highlight examples of animal behavior modification and corresponding nervous system adaptation in res

Recent studies have demonstrated that network approaches are highly appropriate tools to understand the extreme complexity of the aging process. The generality of the network concept helps to define and study the aging of technological, social networks and ecosystems, which may give novel concepts to cure age-related diseases. The current review focuses on the role of protein-protein interaction networks (interactomes) in aging. Hubs and inter-modular elements of both interactomes and signaling networks are key regulators of the aging process. Aging induces an increase in the permeability of several cellular compartments, such as the cell nucleus, introducing gross changes in the representation of network structures. The large overlap between aging genes and genes of age-related major diseases makes drugs which aid healthy aging promising candidates for the prevention and treatment of age-related diseases, such as cancer, atherosclerosis, diabetes and neurodegenerative disorders. We also discuss a number of possible research options to further explore the potential of the network concept in this important field, and show that multi-target drugs (representing "magic-buckshots" inste

Addressing the unavoidable bias inherent in supervised aging clocks, we introduce Sundial, a novel framework that models molecular dynamics through a diffusion field, capturing both the population-level aging process and the individual-level relative aging order. Sundial enables unbiasedestimation of biological age and the forecast of aging roadmap. Fasteraging individuals from Sundial exhibit a higher disease risk compared to those identified from supervised aging clocks. This framework opens new avenues for exploring key topics, including age- and sex-specific aging dynamics and faster yet healthy aging paths.

The study and development of software able to show the effect of aging of faces is one of the tasks of face recognition technologies. Some software solutions are used for investigations, some others to show the effects of drugs on healthy appearance, however some other applications can be proposed for the analysis of visual arts. Here we use a freely available software, which is providing interesting results, for the comparison of ancient marble busts. An analysis of Augustus busts is proposed.

We investigate the effects of aging in the noisy voter model considering that the probability to change states decays algebraically with age $τ$, defined as the time elapsed since adopting the current state. We study the complete aging scenario, which incorporates aging to both mechanisms of interaction: herding and idiosyncratic behavior, and compare it with the partial aging case, where aging affects only the herding mechanism. Analytical mean-field equations are derived, finding excellent agreement with agent-based simulations on a complete graph. We observe that complete aging enhances consensus formation, shifting the critical point to higher values compared to the partial aging case. However, when the aging probability decays asymptotically to zero for large $τ$, a steady state is not always attained for complete aging.

Motivated by recent research of aging in E. coli, we explore the effects of aging on bacterial fitness. The disposable soma theory of aging was developed to explain how differences in lifespans and aging rates could be linked to life history trade-offs. Although generally applied for multicellular organisms, it is also useful for exploring life history strategies of single celled organisms such as bacteria. Starting from the Euler-Lotka equation, we propose a mathematical model to explore how a finite lifespan effects fitness of bacteria. We find that that there is surprisingly little loss of fitness when the bacterium has limited opportunities to reproduce. Instead, the fitness gained each time the bacteria reproduces decreases rapidly, and investing resources to survive to reproduce the first few times is likely more advantageous than investing additional resources to try to maintain cell integrity longer.

Face aging is an ill-posed problem because multiple plausible aging patterns may correspond to a given input. Most existing methods often produce one deterministic estimation. This paper proposes a novel CLIP-driven Pluralistic Aging Diffusion Autoencoder (PADA) to enhance the diversity of aging patterns. First, we employ diffusion models to generate diverse low-level aging details via a sequential denoising reverse process. Second, we present Probabilistic Aging Embedding (PAE) to capture diverse high-level aging patterns, which represents age information as probabilistic distributions in the common CLIP latent space. A text-guided KL-divergence loss is designed to guide this learning. Our method can achieve pluralistic face aging conditioned on open-world aging texts and arbitrary unseen face images. Qualitative and quantitative experiments demonstrate that our method can generate more diverse and high-quality plausible aging results.

Recent results of an aging test performed at the CERN Gamma Irradiation Facility on a single--gap RPC prototype developed for the LHCb Muon System are presented. The results are based on an accumulated charge of about 0.45 C/cm$^2$, corresponding to about 4 years of LHCb running at the highest background rate. The performance of the chamber has been studied under several photon flux values exploiting a muon beam. A degradation of the rate capability above 1 kHz/cm$^2$ is observed, which can be correlated to a sizeable increase of resistivity of the chamber plates. An increase of the chamber dark current is also observed. The chamber performance is found to fulfill the LHCb operation requirements.