Physiology最新文献

Understanding the neural mechanisms of memory has been one of the key questions in biology. Long-term memory, specifically, allows one to travel mentally without constraints of time and space. A long-term memory must have gone through a series of temporal processes: encoding, consolidation, storage, and retrieval. Decades of studies have revealed cellular and molecular mechanisms underlying each process. In this article, we first review the emerging concept of memory engrams and technologies of engram labeling, as these methods provide a new avenue to study the molecular mechanisms for memory. Then, we focus on DNA methylation and its role in long-term memory. Finally, we discuss some key remaining questions in this field and their implications in memory-related disease.

Reflecting on the diversity of the natural world, Darwin famously observed that "from so simple a beginning endless forms most beautiful and most wonderful have been, and are being evolved." However, the examples that we are able to observe in nature are a consequence of chance, constrained by selection, drift, and epistasis. Here we explore how the efforts of synthetic biology to build new living systems can expand our understanding of the fundamental design principles that allow life to self-organize biological form, from cellular to organismal levels. We suggest that the ability to impose a length or timescale onto a biological activity is an essential strategy for self-organization in evolved systems and a key design target that is now being realized synthetically at all scales. By learning to integrate these strategies together, we are poised to expand on evolution's success and realize a space of synthetic forms not only beautiful but with diverse applications and transformative potential.

Hormones orchestrate virtually all physiological processes in animals and enable them to adjust internal responses to meet diverse physiological demands. Studies in both vertebrates and insects have uncovered many novel hormones and dissected the physiological mechanisms they regulate, demonstrating a remarkable conservation in endocrine signaling across the tree of life. In this review, we focus on recent advances in insect research, which have provided a more integrative view of the conserved interorgan communication networks that control physiology. These new insights have been driven by experimental advantages inherent to insects, which over the past decades have aligned with new technologies and sophisticated genetic tools, to transform insect genetic models into a powerful testbed for posing new questions and exploring longstanding issues in endocrine research. Here, we illustrate how insect studies have addressed classic questions in three main areas, hormonal control of growth and development, neuroendocrine regulation of ion and water balance, and hormonal regulation of behavior and metabolism, and how these discoveries have illuminated our fundamental understanding of endocrine signaling in animals. The application of integrative physiology in insect systems to questions in endocrinology and physiology is expanding and is poised to be a crucible of discovery, revealing fundamental mechanisms of hormonal regulation that underlie animal adaptations to their environments.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating multisystem disorder of unclear etiology that affects many individuals worldwide. One of its hallmark symptoms is prolonged fatigue following exertion, a feature also observed in long COVID, suggesting an underlying dysfunction in energy production in both conditions. Here, mitochondrial dysfunction and its potential pathogenetic role in these disorders are reviewed.

Nicotinamide adenine dinucleotide (NAD⁺), a coenzyme in cellular metabolism, has never ceased to capture the fascination of scientists since its discovery in 1906. The expansion of NAD⁺'s function from cellular metabolism to DNA repair, gene regulation, cell signaling, and aging reflects the central role of cellular metabolism in orchestrating the diverse cellular pathways. In the past decade, NAD⁺ has emerged as a key regulator of stem cells, opening the door to potential approaches for regenerative medicine. Here we reflect on how the field of NAD⁺ regulation of stem cells has evolved since a decade ago, when sirtuins, NAD⁺-dependent enzymes, were shown to be critical regulators of stem cells. We review the recent development on how NAD⁺ is regulated in stem cells to influence fate decision. We discuss the difference in NAD⁺ regulation of normal and cancer stem cells. Finally, we consider the consequences of NAD⁺ regulation of stem cells for health and diseases.

Aging is a multifaceted process associated with a functional decline in cellular function over time, affecting all lifeforms. During the aging process, metabolism, a fundamental hallmark of life (1), is profoundly altered. In the context of hematopoiesis, the proper function of hematopoietic stem cells, at the apex of the blood system, is tightly linked to their energy metabolism, which in turn shapes hematopoietic output. Here, we review the latest developments in our understanding of the metabolic states and changes in aged hematopoietic stem cells, molecular players and pathways involved in aged hematopoietic stem cell metabolism, the consequences of perturbed metabolism on clonal hematopoiesis and leukemogenesis, and pharmacologic/genetic strategies to reverse or rejuvenate altered metabolic phenotypes.

As life expectancy increases globally, the prevalence and severity of age-related diseases have risen, significantly impacting patients' quality of life and increasing dependency on the healthcare system. Age-related diseases share several pathological commonalities, and emerging evidence suggests that targeting these biological processes ameliorates multiple age-related diseases. Immune aging plays a critical role in the pathogenesis of age-related diseases, given its involvement not only in controlling infection and cancer but also in facilitating tissue homeostasis and repair. Aging causes compositional and functional changes in both innate and adaptive immune cells, thereby significantly contributing to the pathogenesis of age-related disease and systemic low-grade inflammation, termed "inflammaging." This review article aims to describe the current understanding of immune aging and its impact on age-related diseases with particular emphasis on kidney and autoimmune diseases. In addition, this review highlights tertiary lymphoid structures (TLS) as a hallmark of immune aging, exploring their roles in inflammation, tissue damage, and potential therapeutic targeting.