Life Of Organism Research Articles

Transport of ‘Nama’‐type biota in sediment gravity and combined flows: Implications for terminal Ediacaran palaeoecology

ABSTRACTThe lower Nama Group in southern Namibia contains trace fossils and soft‐bodied and biomineralized macro‐organisms from the terminal Ediacaran Period (ca 550 to 539 Ma), offering insights into early metazoan evolution. Interpretation of the fossilized Nama Group organisms as being preserved in, or very close to, the environments in which they originally lived has yielded insights into organism feeding habits, reproduction and life histories. Sedimentological evidence presented here reveals that typical ‘Nama‐type’ Ediacaran macro‐fossils (Cloudina, Ernietta, Pteridinium and Rangea) in the Dabis and Zaris formations of the Witputz Sub‐basin seldom preserve organisms in life position in their original palaeoenvironments. Both soft‐bodied and biomineralizing organisms were transported in sediment gravity flows (debris flows, turbidity flows and transitional debris flow‐turbidity flow ‘hybrid’ event beds) or combined flow (hummocky cross‐strata) to their terminal environment of deposition in shoreface and offshore shelf settings. Transport has placed studied beds and their associated macro‐organisms in depositional settings detached from the original life habitat, with macro‐organisms sourced from shallower‐water, up‐slope environments. Integrated sedimentological and palaeontological data indicate that the Nama Group may not provide a high‐fidelity record of original Nama ecosystems. Individual macro‐organisms are clasts within beds, and can be horizontal, imbricated or chaotic in orientation. Transport can blend different communities at various scales (bed, outcrop and basin), complicating interpretations of life habitats, species interactions and taxon‐specific ecology, such as feeding behaviour and life position of organisms. Recognition of organism transport also impacts datasets used for comparing global Ediacaran fossil assemblages, with implications for tracking spatial and temporal patterns in early animal evolution.

Bone infection evolution

The present minireview aims to provide a context for imagination of the timespan for bone infection evolution from the origin of cellular bone tissue to modern orthopedic surgery. From a phylogenetic osteomyelitis-bracketing perspective, and due to the time of osteocyte origin, bacteria might have been able to infect the skeleton for approximately 400 million years. Thereby, bone infections happened simultaneously with central expansions of the immune system and development of terrestrial bone structure. This co-evolution might aid in explaining the many immune evasion strategies seen in the field of bone infections. Bone infection patients with long disease-free periods followed by sudden recurrence and anamnesis of long-term and low-grade infections indicate that bacteria can perform silent parasitism within bone tissue (parasitism; one organism lives on another organism, the host, causing it harm and is structurally adapted to it). The silence seems to be disturbed by immunosuppression and the present minireview shows that a compromised immune system has been associated with bone infection development across all species in the phylogenetic tree. Orthopedic surgery, including arthroplasty and osteosynthesis, favor introduction of bacteria and prosthesis/implant related infections are thus anthropogenic infections (anthropogenic; resulting from the influence of human beings on nature). In that light it is important to remember that the skeleton and immune system have not evolved for millions of years to protect titanium alloys and other metals, commonly used for orthopedic devices from bacterial invasion. Therefore, these relatively new orthopedic infection types must be seen as distinct with unique implant/prosthesis related pathophysiology and immunology.

Environmental legislation analysis improvement approach of global marine plastic pollution from the perspective of holistic system view

Marine plastic pollution (MPP) has posed an unavoidable challenge to the conservation of marine ecosystems, escalating at an unprecedented rate. It extends beyond visible pollution, infiltrating the food chain and microcirculation, ultimately affecting the life and health of marine organisms. Of even greater concern is the fact that MPP has been found to penetrate human bloodstreams. The international community increasingly focuses on MPP, and has formulated a series of laws and regulations. This article analyses marine pollution prevention legislation within the context of international environmental resolutions and conventions, including those established by the United Nations, the European Union law and the domestic legislation of sovereign states. It is evident that the current legislation has played a pivotal role in the preventing MPP. However, global legislation on preventing MPP remains fragmented. The problems existing in the current legislation should be reviewed from the holistic systems perspective, and the integrity and systematicness of new plastics convention should be demonstrated. The proposed Marine Plastics Convention should emphasize environmental justice, protect the rights of vulnerable populations, lower the threshold for risk prevention, and focus on addressing residual risks. It must include clear provisions for regulating hydrosphere plastic pollution (HPP) to mitigate land-based pollution and scientifically define fundamental legal concepts to foster coordinated action among States. Moreover, the convention should establish standardized monitoring methodologies and assessment criteria to ensure accurate evaluation of the pollution status.

Calorie restriction increases insulin sensitivity to promote beta cell homeostasis and longevity in mice

Caloric restriction (CR) can extend the organism life- and health-span by improving glucose homeostasis. How CR affects the structure-function of pancreatic beta cells remains unknown. We used single nucleus transcriptomics to show that CR increases the expression of genes for beta cell identity, protein processing, and organelle homeostasis. Gene regulatory network analysis reveal that CR activates transcription factors important for beta cell identity and homeostasis, while imaging metabolomics demonstrates that beta cells upon CR are more energetically competent. In fact, high-resolution microscopy show that CR reduces beta cell mitophagy to increase mitochondria mass and the potential for ATP generation. However, CR beta cells have impaired adaptive proliferation in response to high fat diet feeding. Finally, we show that long-term CR delays the onset of beta cell aging hallmarks and promotes cell longevity by reducing beta cell turnover. Therefore, CR could be a feasible approach to preserve compromised beta cell structure-function during aging and diabetes.

Sitetack: a deep learning model that improves PTM prediction by using known PTMs.

Post-translational modifications (PTMs) increase the diversity of the proteome and are vital to organismal life and therapeutic strategies. Deep learning has been used to predict PTM locations. Still, limitations in datasets and their analyses compromise success. We evaluated the use of known PTM sites in prediction via sequence-based deep learning algorithms. For each PTM, known locations of that PTM were encoded as a separate amino acid before sequences were encoded via word embedding and passed into a convolutional neural network that predicts the probability of that PTM at a given site. Without labeling known PTMs, our models are on par with others. With labeling, however, we improved significantly upon extant models. Moreover, knowing PTM locations can increase the predictability of a different PTM. Our findings highlight the importance of PTMs for the installation of additional PTMs. We anticipate that including known PTM locations will enhance the performance of other proteomic machine learning algorithms. Sitetack is available as a web tool at https://sitetack.net; the source code, representative datasets, instructions for local use, and select models are available at https://github.com/clair-gutierrez/sitetack.

Productive foraging grounds enhance maternal condition and offspring quality in a capital breeding species.

Feeding ecology is an essential component of an organism's life, but foraging comes with risks and energetic costs. Species in which populations exhibit more than one feeding strategy, such as sea turtles, are good systems for investigating how feeding ecology impacts life-history traits, reproduction and carried over effects across generations. Here, we investigated how the feeding ecology of loggerhead sea turtles (Caretta caretta) nesting at the Cabo Verde archipelago correlates with reproductive outputs and offspring quality. We determined the feeding ecology of female turtles before and during the breeding season from stable isotope analysis of carbon and nitrogen and correlated isotopic ratio with female and offspring traits. We found that female turtles feeding at higher trophic positions produced larger clutches. We also found that females with higher δ13C values, typical of productive foraging areas, had greater fat reserves, were less likely to be infected by leech parasites and produced heavier offspring. The offspring of infected mothers with higher δ13C values performed best in crawling and self-righting trials than those of non-infected mothers with higher δ13C values. This study shows adult female loggerheads that exploit productive areas build capital reserves that impact their reproductive success and multiple proxies for offspring quality. Overall, our findings provide valuable insights into the complex interplay between feeding ecology and reproductive success, and reveal the transgenerational carry-over effects of both feeding ecology and health on offspring quality in sea turtles.

Variability of biophysical parameters during La Niña condition in the Eastern Region of the Indian Ocean

The La Niña event not only affected global ocean dynamics but also marine productivity. Due to its importance to the life of organisms and ecosystems, the biophysical aspects should be analyzed. One of the important regions in the eastern region of the Indian Ocean is located in the upwelling system and central marine biodiversity. The study aims to investigate several parameters, including SSTs, dissolved oxygen levels, nitrate distribution, and Chlor-a concentration, which are combined with ocean currents. These parameters are then analyzed in the period 2020 to 2022, which is La Niña condition. Based on the results, significant changes occur in SST during the first transitional season of 2022, where the increase reaches 1–4 °C. There was an increase in La Niña during this period. For marine productivity parameters, the recorded DO is in the range of 197 to 218 mmol/m3, nitrate with a value range of 0 to 0,02 mmol/m3, nanoplankton with a value range of 0 to 0.03 mg/m3, and Chlor-a with a value range of 0 to 4 mg/m3. We also found that changes in ENSO events affect the productivity of the Eastern Region of the Indian Ocean, especially in the Chlor-a parameter, where the occurrence of La Niña extreme is the most important parameter.

Hazard assessment of microplastics and heavy metals contamination in Levant frogs (Pelophylax bedriagae): A bioindicator in Western Iran

The increasing pollution of aquatic ecosystems caused by microplastics (MPs) and heavy metal ions worldwide threatens the life of aquatic organisms, including amphibians. In this study, we investigated the presence and accumulation of MPs and heavy metal ions in the upper gastrointestinal tract (GIT) of the Levant frog (Pelophylax bedriagae) as a bioindicator in contaminated sites of Western Iran. A total of 192 adult frogs from 16 locations in the west and northwest of Iran were collected. We measured the accumulation of MPs and heavy metal ions in the collected frogs and determined the characteristics of MPs in the samples. Our findings revealed widespread MPs and heavy metal ions contamination in the frog GIT across all sampled stations. We found 742 MP particles in the digestive system of frogs, with the highest (7.09 MP/individual) and lowest (2.37 MP/individual) number observed in stations 10 and 9, respectively. Fibers were the most common MPs and polyester (PES) (42.5%) and polyethylene terephthalate (PET) (17.2%) were found to be the most common polymers in the GIT of frogs. The average accumulation of heavy metal ions showed significant differences (P < 0.05) among 16 sampling stations, and zinc (II) and mercury (II) showed the highest and lowest concentrations in frogs. We also found moderate to strong positive correlations between the detected MPs and heavy metal ions in the frog samples across all sampling stations. Our findings confirm the contamination of frogs by MPs and heavy metal ions and the potential capacity of MPs to increase the toxicity of heavy metals in P. bedriagae as a bioindicator in contaminated sites.

B-BIND: Biophysical Bayesian Inference for Neurodegenerative Dynamics.

Throughout an organism's life, a multitude of complex and interdependent biological systems transition through biophysical processes that serve as indicators of the underlying biological states. Inferring these latent, unobserved states is a goal of modern biology and neuroscience. However, in many experimental setups, we can at best obtain discrete snapshots of the system at different times and for different individuals. This challenge is particularly relevant in the study of Alzheimer's Disease (AD) progression, where we observe the aggregation of pathology in brain donors, but the underlying disease state is unknown. This paper proposes a biophysically motivated Bayesian framework (B-BIND: Biophysical Bayesian Inference for Neurodegenerative Dynamics), where the disease state is modeled and continuously inferred from observed quantifications of multiple AD pathological proteins. Inspired by biophysical models, we describe pathological burden as an exponential process. The progression of AD is modeled by assigning a latent score, termed pseudotime, to each pathological state, creating a pseudotemporal order of donors based on their pathological burden. We study the theoretical properties of the model using linearization to reveal convergence and identifiability properties. We provide Markov chain Monte Carlo estimation algorithms, illustrating the effectiveness of our approach with multiple simulation studies across various data conditions. Applying this methodology to data from the Seattle Alzheimer's Disease Brain Cell Atlas, we infer the pseudotime ordering of donors. Finally, we analyze the information within each pathological feature to refine the model, focusing on the most informative pathologies. This framework lays the groundwork for continuous pseudotime modeling in the analysis of neurodegenerative diseases.

Macrozoobenthos Communities Found In The Waters Of Mariah Bandar Springs

Macrozoobenthos found in the waters of Mariah Bandar Springs, Pematang Bandar District, Simalungun Regency, along with physical and chemical parameters, where biological samples, namely macrozoobenthos, were taken using a quadrant and physical and chemical parameters of the water were taken using a dark colored sample bottle and then analyzed at the BTKL The waters that originate from the Mariah Bandar spring have very clear and shallow water, so that the bottom of the waters (substrate) can be seen directly, which consists of sandy rocks. The macrozoobenthos community in the waters of Mariah Bandar spring consists of four classes, namely Clitellata, Gastropod, Bivalvia, Insecta, and eight families, namely Lumbricidae, Thiaridae, Cyrenidae, Chironomidae, Gomphidae, Paludicola, Coenagrionidae, Libellulidae. The temperature at each observation station ranges from 220C – 350C, brightness ranges from 4 – 4.5 m from the surface, dissolved oxygen (DO) ranges from 6.84-8.25 mg/l, pH ranges from 7.36-8.85 , BOD ranged from 1.01-3.42 mg/l. In general, the physical and chemical parameters measured still support the life of freshwater organisms, unless the pH is classified as acid.

Response of fruit fly (Drosophila pseudoobscura) to diet manipulation of nutrient density

AbstractCaloric intake can greatly affect many aspects of an organism's life. A deficiency of calories can lead to stress resulting in decreased fecundity, insufficient calories to maintain tissues and increased lifespan. Conversely, increasing caloric density increases fecundity and decreases lifespan. Despite decades of work exploring food quality and quantity on physiology in the model species Drosophila melanogaster Meigan 1830 (Diptera: Drosophilidae) and the melanogaster group in general, relatively little work explores the physiological responses to diet manipulation in other Drosophila species, like the obscura species group. Here, we looked at the effects of five different caloric densities (0.5×, 0.75×, 1.0×, 1.5× and 3.0×) on food intake, body weight, body fat, fecundity and longevity in D. pseudoobscura Frolova &amp; Astaurov, 1929 (Diptera: Drosophilidae). Comparing longevity and fecundity across diets, we found that heavy caloric concentration (3.0×) decreases lifespan and that calorie restriction (0.5× and 0.75×) led to significant decreases in fecundity and body weight. However, calorie concentration did not significantly increase D. pseudoobscura body fat. By expanding our understanding of the physiological responses to diet stress to D. pseudoobscura, we establish the framework for comparative work across Drosophila species. With this information, we can then identify which physiological responses to diet manipulation might be most conserved and comparable across species.

Land of the giants: Body mass estimates of Palaeoloxodon from the Pleistocene of Taiwan

The sea bottom of Taiwan Strait harbors a Late Pleistocene paleo-ecosystem significantly distinct from the present ecosystem structure in Taiwan. The assemblage constitutes fossil remains from the genus Palaeoloxodon, the largest known lineage of proboscideans to have walked on Earth. Body mass holds a pivotal role in our understanding of an organism's biology, ecology, life history, and susceptibility to extinction, and thus, is a key trait while working with extinct taxa. Here we, for the first time, assess the body mass of Palaeoloxodon specimens from Taiwan using well-established allometric scaling equations derived from both extant and extinct species. Our results indicate that Palaeoloxodon individuals from Taiwan exceed 10 tonnes in body mass with a mean body mass of 9.32 tonnes, similar in size to Palaeoloxodon antiquus across Eurasia, and an average shoulder height of 3.49 m. Additionally, our statistical pairwise analysis of body mass distribution shows that Palaeoloxodon specimens from Taiwan significantly differ from the largest species in the genus, Palaeoloxodon namadicus. We further employ equations from extant proboscideans and show notable discrepancies due to differences in body shape between extinct and extant proboscideans. Our estimated body masses offer novel insights into the paleoecology and extinction pressures of the Palaeoloxodon population during the Pleistocene of Taiwan. Further research promises to reveal the habitats capable of sustaining megafaunal populations and extinction events along the easternmost margin of Eurasia.

Preliminary studies of selected Lemna species on the oxygen production potential in relation to some ecological factors.

Dissolved oxygen is fundamental for chemical and biochemical processes occurring in natural waters and critical for the life of aquatic organisms. Many organisms are responsible for altering organic matter and oxygen transfers across ecosystem or habitat boundaries and, thus, engineering the oxygen balance of the system. Due to such Lemna features as small size, simple structure, vegetative reproduction and rapid growth, as well as frequent mass occurrence in the form of thick mats, they make them very effective in oxygenating water. The research was undertaken to assess the impact of various species of duckweed (L. minor and L. trisulca) on dissolved oxygen content and detritus production in water and the role of ecological factors (light, atmospheric pressure, conductivity, and temperature) in this process. For this purpose, experiments were carried out with combinations of L. minor and L. trisulca. On this basis, the content of oxygen dissolved in water was determined depending on the growth of duckweed. Linear regression models were developed to assess the dynamics of changes in oxygen content and, consequently, organic matter produced by the Lemna. The research showed that the presence of L. trisulca causes an increase in dissolved oxygen content in water. It was also shown that an increase in atmospheric pressure had a positive effect on the ability of duckweed to produce oxygen, regardless of its type. The negative correlation between conductivity and water oxygenation, obtained in conditions of limited light access, allows us to assume that higher water conductivity limits oxygen production by all combinations of duckweeds when the light supply is low. Based on the developed models, it was shown that the highest increase in organic matter would be observed in the case of mixed duckweed and the lowest in the presence of the L. minor species, regardless of light conditions. Moreover, it was shown that pleustophytes have different heat capacities, and L. trisulca has the highest ability to accumulate heat in water for the tested duckweed combinations. The provided knowledge may help determine the good habitat conditions of duckweed, indicating its role in purifying water reservoirs as an effect of producing organic matter and shaping oxygen conditions with the participation of various Lemna species.

The Mechanics of Building Functional Organs.

Organ morphogenesis is multifaceted, multiscale, and fundamentally a robust process. Despite the complex and dynamic nature of embryonic development, organs are built with reproducible size, shape, and function, allowing them to support organismal growth and life. This striking reproducibility of tissue form exists because morphogenesis is not entirely hardwired. Instead, it is an emergent product of mechanochemical information flow, operating across spatial and temporal scales-from local cellular deformations to organ-scale form and function, and back. In this review, we address the mechanical basis of organ morphogenesis, as understood by observations and experiments in living embryos. To this end, we discuss how mechanical information controls the emergence of a highly conserved set of structural motifs that shape organ architectures across the animal kingdom: folds and loops, tubes and lumens, buds, branches, and networks. Moving forward, we advocate for a holistic conceptual framework for the study of organ morphogenesis, which rests on an interdisciplinary toolkit and brings the embryo center stage.

The Self-ish Gene: Retroactive Tropes in Richard Dawkins’s Evolutionary Logic

ABSTRACT Building on recent developments in Lacanian rhetorical criticism, this essay demonstrates how contemporary evolutionary theory posits genetic determinism without a clear definition of the gene. It makes this case through close readings of Richard Dawkins’s The Selfish Gene, the landmark text of neo-Darwinian genetics. It demonstrates how Dawkins uses metaphors to substitute a single determinate agent in place of the genome’s essential complexity. Despite Dawkins’s admission that he could not define the gene, his metaphors give his “self-ish gene” a sense of unity and coherence that allows him to describe all other levels of life (organisms, species, ecosystems) as reducible to it. Dawkins’s use of metaphor leverages a broader reductionist logos, one that operates in discourses far beyond the biological. Methodologically, the essay advances the study of scientific metaphor by focusing on the formal properties of metaphor and the ways they afford logical closure.

Genetic drift drives faster-Z evolution in the salmon louse Lepeophtheirus salmonis.

How sex chromosomes evolve compared to autosomes remains an unresolved question in population genetics. Most studies focus on only a handful of taxa, resulting in uncertainty over whether observed patterns reflect general processes or idiosyncrasies in particular clades. For example, in female heterogametic (ZW) systems, bird Z chromosomes tend to evolve quickly but not adaptively, while in Lepidopterans they evolve adaptively, but not always quickly. To understand how these observations fit into broader evolutionary patterns, we explore Z chromosome evolution outside of these two well-studied clades. We utilize a publicly available genome, gene expression, population, and outgroup data in the salmon louse Lepeophtheirus salmonis, an important agricultural pest copepod. We find that the Z chromosome is faster evolving than autosomes, but that this effect is driven by increased drift rather than adaptive evolution. Due to high rates of female reproductive failure, the Z chromosome exhibits a slightly lower effective population size than the autosomes which is nonetheless to decrease efficiency of hemizygous selection acting on the Z. These results highlight the usefulness of organismal life history in calibrating population genetic expectations and demonstrate the value of the ever-expanding wealth of publicly available data to help resolve outstanding evolutionary questions.

Organismal trade-offs and the pace of planktonic life.

No one is perfect, and organisms that perform well in some habitat or with respect to some tasks, do so at the cost of performance in others: there are inescapable trade-offs. Organismal trade-offs govern the structure and function of ecosystems and attempts to demonstrate and quantify trade-offs have therefore been an important goal for ecologists. In addition, trade-offs are a key component in trait-based ecosystem models. Here, I synthesise evidence of trade-offs in plankton organisms, from bacteria to zooplankton, and show how a slow-fast gradient in life histories emerges. I focus on trade-offs related to the main components of an organism's Darwinian fitness, that is resource acquisition, survival, and propagation. All consumers need to balance the need to eat without being eaten, and diurnal vertical migration, where zooplankton hide at depth during the day to avoid visual predators but at the cost of missed feeding opportunities in the productive surface layer, is probably the best documented result of this trade-off. However, there are many other more subtle but equally important behaviours that similarly are the result of an optimisation of these trade-offs. Most plankton groups have also developed more explicit defence mechanisms, such as toxin production or evasive behaviours that are harnessed in the presence of their predators; the costs of these have often proved difficult to quantify or even demonstrate, partly because they only materialise under natural conditions. Finally, all multicellular organisms must allocate time and resources among growth, reproduction, and maintenance (e.g. protein turnover and DNA repair), and mate finding may compromise both survival and feeding. The combined effects of all these trade-offs is the emergence of a slow-fast gradient in the pace-of-life, likely the most fundamental principle for the organisation of organismal life histories. This crystallisation of trade-offs may offer a path to further simplification of trait-based models of marine ecosystems.

Sitetack: A Deep Learning Model that Improves PTM Prediction by Using Known PTMs.

Post-translational modifications (PTMs) increase the diversity of the proteome and are vital to organismal life and therapeutic strategies. Deep learning has been used to predict PTM locations. Still, limitations in datasets and their analyses compromise success. Here we evaluate the use of known PTM sites in prediction via sequence-based deep learning algorithms. Specifically, PTM locations were encoded as a separate amino acid before sequences were encoded via word embedding and passed into a convolutional neural network that predicts the probability of a modification at a given site. Without labeling known PTMs, our model is on par with others. With labeling, however, we improved significantly upon extant models. Moreover, knowing PTM locations can increase the predictability of a different PTM. Our findings highlight the importance of PTMs for the installation of additional PTMs. We anticipate that including known PTM locations will enhance the performance of other proteomic machine learning algorithms.

Bacterial cell differentiation enables population level survival strategies.

Clonal reproduction of unicellular organisms ensures the stable inheritance of genetic information. However, this means of reproduction lacks an intrinsic basis for genetic variation, other than spontaneous mutation and horizontal gene transfer. To make up for this lack of genetic variation, many unicellular organisms undergo the process of cell differentiation to achieve phenotypic heterogeneity within isogenic populations. Cell differentiation is either an inducible or obligate program. Induced cell differentiation can occur as a response to a stimulus, such as starvation or host cell invasion, or it can be a stochastic process. In contrast, obligate cell differentiation is hardwired into the organism's life cycle. Whether induced or obligate, bacterial cell differentiation requires the activation of a signal transduction pathway that initiates a global change in gene expression and ultimately results in a morphological change. While cell differentiation is considered a hallmark in the development of multicellular organisms, many unicellular bacteria utilize this process to implement survival strategies. In this review, we describe well-characterized cell differentiation programs to highlight three main survival strategies used by bacteria capable of differentiation: (i) environmental adaptation, (ii) division of labor, and (iii) bet-hedging.

The beginning of becoming a human.

According to birth certificates, the life of a child begins once their body comes out of the mother's womb. But when does their organismal life begin? Science holds a palette of answers-depending on how one defines a human life. In 1984, a commission on the regulatory framework for human embryo experimentation opted not to answer this question, instead setting a boundary, 14 days post-fertilization, beyond which any experiments were forbidden. Recently, as the reproductive technologies developed and the demand for experimentation grew stronger, this boundary may be set aside leaving the ultimate decision to local oversight committees. While science has not come closer to setting a zero point for human life, there has been significant progress in our understanding of early mammalian embryogenesis. It has become clear that the 14-day stage does in fact possess features, which make it a foundational time point for a developing human. Importantly, this stage defines the separation of soma from the germline and marks the boundary between rejuvenation and aging. We explore how different levels of life organization emerge during human development and suggest a new meaning for the 14-day stage in organismal life that is grounded in recent mechanistic advances and insights from aging studies.