Oklahoma Nathan Shock Aging Center — assessing the basic biology of aging from genetics to protein and function

Since Robert Hooke first described the existence of ‘cells’ in 1665, scientists have sought to identify and further characterise these fundamental units of life. While our understanding of cell location, morphology and function has expanded greatly; our understanding of cell types and states at the molecular level, and how these function within tissue architecture, is still limited. A greater understanding of our cells could revolutionise basic biology and medicine. Atlasing initiatives like the Human Cell Atlas aim to identify all cell types at the molecular level, including their physical locations, and to make this reference data openly available to the scientific community. This is made possible by a recent technology revolution: both in single-cell molecular profiling, particularly single-cell RNA sequencing, and in spatially resolved methods for assessing gene and protein expression. Here, we review available and upcoming atlasing technologies, the biological insights gained to date and the promise of this field for the future.

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Telomere Length as a Biomarker of Biological Aging in Shift Workers

Applied Sciences ◽

10.3390/app10082764 ◽

2020 ◽

Vol 10 (8) ◽

pp. 2764 ◽

Cited By ~ 2

Author(s):

Caterina Ledda ◽

Carla Loreto ◽

Venerando Rapisarda

Keyword(s):

Telomere Length ◽

Biological Aging ◽

Work Schedule ◽

Shift Workers ◽

Daily Work ◽

Occupational Physicians ◽

Age Related ◽

Health Advice ◽

Basic Biology ◽

Biology Of Aging

Shift work (SW) comprises a work schedule that involves recurring times of nonstandard work hours balanced to a fixed daily work plan with regular day work times and has been evaluated as “probably carcinogenic to humans” (Group 2A) by IARC. SW may result in increased age acceleration. This systematic review aims to elucidate the usefulness of telomere length as a biomarker of biological aging in shift workers. All studies analyzed underline a shortening of telomere length in SW, and aging in shift workers and duration of work. Methodologies to measure biological aging are possible to advance efforts to clarify the basic biology of aging and provide clinicians an instrument to communicate complex health advice to workers. Telomere length measures can also give an instrument for precision medicine, useful for occupational physicians in age-related screening conditions.

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Neuroglia

10.1093/med/9780199794591.001.0001 ◽

2013 ◽

Cited By ~ 42

Author(s):

Bruce R. Ransom

Keyword(s):

Neurological Diseases ◽

Normal Brain ◽

Massive Growth ◽

Full Color ◽

Normal Brain Function ◽

Growth Of Knowledge ◽

Basic Biology ◽

Psychiatric Conditions ◽

And Function ◽

The Brain

This resource is the long-awaited new revision of the most highly regarded reference volume on glial cells, and has been completely revised, greatly enlarged, and enhanced with full color figures throughout. Neglected in research for years, it is now evident that the brain only functions in a concerted action of all the cells, namely glia and neurons. Seventy one chapters comprehensively discuss virtually every aspect of normal glial cell anatomy, physiology, biochemistry and function, and consider the central roles of these cells in neurological diseases including stroke, Alzheimer disease, multiple sclerosis, Parkinson's disease, neuropathy, and psychiatric conditions. With more than 20 new chapters it addresses the massive growth of knowledge about the basic biology of glia and the sophisticated manner in which they partner with neurons in the course of normal brain function.

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Bring Back the Rat!

The Journals of Gerontology Series A ◽

10.1093/gerona/glz298 ◽

2020 ◽

Vol 75 (3) ◽

pp. 405-415 ◽

Cited By ~ 8

Author(s):

Christy S Carter ◽

Arlan Richardson ◽

Derek M Huffman ◽

Steven Austad

Keyword(s):

Complete Characterization ◽

Human Aging ◽

Aging Research ◽

Laboratory Rat ◽

Basic Biology ◽

Biology Of Aging ◽

And Behavior ◽

Compare And Contrast

Abstract As 2020 is “The Year of the Rat” in the Chinese astrological calendar, it seems an appropriate time to consider whether we should bring back the laboratory rat to front-and-center in research on the basic biology of mammalian aging. Beginning in the 1970s, aging research with rats became common, peaking in 1992 but then declined dramatically by 2018 as the mouse became preeminent. The purpose of this review is to highlight some of the historical contributions as well as current advantages of the rat as a mammalian model of human aging, because we suspect at least a generation of researchers is no longer aware of this history or these advantages. Herein, we compare and contrast the mouse and rat in the context of several biological domains relevant to their use as appropriate models of aging: phylogeny/domestication, longevity interventions, pathology/physiology, and behavior/cognition. It is not the goal of this review to give a complete characterization of the differences between mice and rats, but to provide important examples of why using rats as well as mice is important to advance our understanding of the biology of aging.

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Ret Signaling Is Required for Tooth Pulp Innervation during Organogenesis

Journal of Dental Research ◽

10.1177/0022034519837971 ◽

2019 ◽

Vol 98 (6) ◽

pp. 705-712 ◽

Cited By ~ 1

Author(s):

C.R. Donnelly ◽

A.A. Shah ◽

E.B. Suh ◽

B.A. Pierchala

Keyword(s):

Dental Pulp ◽

Substantial Reduction ◽

Cell Types ◽

Conditional Knockout ◽

Tooth Pulp ◽

Spatiotemporal Regulation ◽

Basic Biology ◽

And Function ◽

Tooth Innervation

During organogenesis, the timing and patterning of dental pulp innervation require both chemoattractive and chemorepellent cues for precise spatiotemporal regulation. Our understanding of the signaling mechanisms that regulate tooth innervation during development, as well as the basic biology of these sensory neurons, remains rudimentary. In this study, we analyzed the expression and function of glial cell line–derived neurotrophic factor (GDNF) and its receptor tyrosine kinase, Ret, in the regulation of innervation of the mouse tooth pulp by dental pulpal afferent (DPA) neurons of the trigeminal ganglion (TG). Using reporter mouse models, we demonstrate that Ret is highly expressed by a subpopulation of DPA neurons projecting to the tooth pulp at both postnatal day 7 (P7) and in the adult. In the adult tooth, GDNF is highly expressed by many cell types throughout the dental pulp. Using a ubiquitous tamoxifen (TMX)–inducible Cre ( UBC-Cre/ERT2) line crossed to Ret conditional knockout mice ( Retfx/fx), Ret was deleted immediately prior to tooth innervation, and the neural projections into P7 molars were analyzed. TMX treatment was efficient in ablating >95% of Ret protein. We observed that UBC-Cre/ERT2; Retfx/fx mice had a significant reduction in the total number of neurites present within the pulp at P7, with a significant accumulation of aberrant fibers in the dental follicle and periodontium. In agreement with these findings, inhibition of Ret signaling through in vivo administration of a highly specific pharmacologic inhibitor (1NM-PP1) of Ret also caused a substantial reduction in pulpal innervation. Taken together, these findings indicate that Ret signaling regulates the timing and patterning of tooth innervation by dental primary afferent neurons of the TG during organogenesis and provide a rationale to explore whether alterations in the GDNF-Ret pathway contribute to pathophysiological conditions in the adult dentition.

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Recent Advances in Three-Dimensional Multicellular Spheroid Culture and Future Development

Micromachines ◽

10.3390/mi12010096 ◽

2021 ◽

Vol 12 (1) ◽

pp. 96

Author(s):

Honglin Shen ◽

Shuxiang Cai ◽

Chuanxiang Wu ◽

Wenguang Yang ◽

Haibo Yu ◽

...

Keyword(s):

Three Dimensional ◽

Multicellular Spheroids ◽

Three Dimensional Model ◽

Advantages And Disadvantages ◽

High Throughput Drug Screening ◽

Tumor Research ◽

Basic Biology ◽

And Function

Three-dimensional multicellular spheroids (MCSs) have received extensive attention in the field of biomedicine due to their ability to simulate the structure and function of tissues in vivo more accurately than traditional in vitro two-dimensional models and to simulate cell–cell and cell extracellular matrix (ECM) interactions. It has become an important in vitro three-dimensional model for tumor research, high-throughput drug screening, tissue engineering, and basic biology research. In the review, we first summarize methods for MCSs generation and their respective advantages and disadvantages and highlight the advances of hydrogel and microfluidic systems in the generation of spheroids. Then, we look at the application of MCSs in cancer research and other aspects. Finally, we discuss the development direction and prospects of MCSs

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Cilia-mediated Hedgehog signaling controls form and function in the mammalian larynx

eLife ◽

10.7554/elife.19153 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 31

Author(s):

Jacqueline M Tabler ◽

Maggie M Rigney ◽

Gordon J Berman ◽

Swetha Gopalakrishnan ◽

Eglantine Heude ◽

...

Keyword(s):

Hedgehog Signaling ◽

Animal Communication ◽

Molecular Genetic ◽

Form And Function ◽

Vocal Apparatus ◽

Important Challenge ◽

Genetic Mechanisms ◽

Basic Biology ◽

Mechanisms Of Development ◽

And Function

Acoustic communication is fundamental to social interactions among animals, including humans. In fact, deficits in voice impair the quality of life for a large and diverse population of patients. Understanding the molecular genetic mechanisms of development and function in the vocal apparatus is thus an important challenge with relevance both to the basic biology of animal communication and to biomedicine. However, surprisingly little is known about the developmental biology of the mammalian larynx. Here, we used genetic fate mapping to chart the embryological origins of the tissues in the mouse larynx, and we describe the developmental etiology of laryngeal defects in mice with disruptions in cilia-mediated Hedgehog signaling. In addition, we show that mild laryngeal defects correlate with changes in the acoustic structure of vocalizations. Together, these data provide key new insights into the molecular genetics of form and function in the mammalian vocal apparatus.

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The Translational Geroscience Network: Supporting a New Paradigm to Alleviate Age-Related Chronic Disease

Innovation in Aging ◽

10.1093/geroni/igaa057.3042 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 831-831

Author(s):

Jamie Justice ◽

Stephen Kritchevsky ◽

George Kuchel ◽

James Kirkland

Keyword(s):

Biological Aging ◽

Small Scale ◽

New Paradigm ◽

Aging Research ◽

Age Related ◽

Treatment Focus ◽

Working Together ◽

Basic Biology ◽

Biology Of Aging ◽

Traditional Approaches

Abstract Aging is the leading risk factor for many chronic diseases. Through traditional approaches to drug development and treatment focus on treating one disease at a time, the geroscience hypothesis posits that by targeting fundamental aging processes one could alleviate multiple age-related diseases. Now several geroscience-guided interventions are at the point of entering human clinical trials. To accelerate testing of this important hypothesis, an interdisciplinary Translational Geroscience Network (TGN; R33 AG061456) has recently been established. The TGN is a new national resource of aging research centers committed to working together toward complementary, small-scale, proof-of-concept “use case” clinical studies. One such pilot will be highlighted: a translational trial of senolytics, or drugs targeting the biological aging process cellular senescence in patients with idiopathic pulmonary fibrosis. The promise of geroscience provides another reason “why age matters”: by studying the basic biology of aging, we may open novel therapeutic opportunities for challenging age-related diseases.

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