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Most somatic cells of long-lived species undergo telomere shortening throughout life. Critically short telomeres trigger loss of cell viability in tissues, which has been related to alteration of tissue function and loss of regenerative capabilities in aging and aging-related dis ...

Epigenetic alterations of DNA play key roles in determining gene structure and expression. Methylation of the 5-position of cytosine is thought to be the most common modification of the genome in mammals. Studies have generally shown that hypermethylation in gene regulatory regions is a ...

The methylation of CpG dinucleotides located in key protein binding sites within gene regulatory regions often leads to gene silencing. A mechanism of aging is proposed whereby an accumulation of methylation at gene regulatory sites contributes to cellular senescence. DNA methyltr ...

The chronological life span of yeast, which is measured as the survival time of populations of nondividing cells, has been used successfully for the identification of key pathways responsible for the regulation of aging. These pathways have remarkable similarities with those that regu ...

The diet known as caloric restriction (CR) has been known for 70 yr to extend the life span of rodents (1). CR can also extend life span in a broad range of other species as well, from unicellular organisms (2,3), to invertebrates (4) and most likely primates, as well (5). The budding yeast Saccharomyces cerevis ...

Measurements of renal clearance, including the measurement of the glomerular filtration rate (GFR), renal plasma flow (RPF), and electrolyte excretion rate, form the foundation for evaluating kidney function in the intact organism. Although much of our current knowledge regarding ...

Proteomics approaches can be useful in identifying biomarkers of renal disease as well as in understanding biological processes specific to renal function. When combined with laser-capture microdissection (LCM), proteomics techniques can identify biomarkers that are speci ...

The kidneys are not only intimately involved in the long-term regulation of blood pressure (BP), but hypertension per se leads to secondary alterations in renal function (1–4). Moreover, the kidneys are a major target site for end-organ hypertensive damage. Indeed, hypertension plays a domi ...

Renin is an aspartyl peptidase that is synthesized, stored, and released from juxtaglomerular (JG) granular cells in the lamina media of the afferent arteriole. Each afferent arteriole contains 5–20 JG cells. Renin catalyzes the cleavage of angiotensin I (ANG I) from renin substrate; angio ...

Mitochondrial oxidative phosphorylation generates 20-fold greater amounts of adenosine triphosphate (ATP) through pyruvate oxidation to CO2 than anaerobic glycolysis, which produces ATP by enzymatic reactions from glucose to pyruvate. In the kidney, proximal tubules are a ...

Segmentation of the nephron relative to transport mechanisms and secretory activity has been recognized for decades, beginning with the pioneering studies of Alfred Newton Richards (1). Nephron segmentation regarding transcellular sodium and water movement has been subject ...

Nitric oxide (NO) is a diatomic free-radical product of mammalian cells that has diverse and important physiological functions, including the regulation of renal, cardiovascular, pulmonary, gastrointestinal, neuronal, inflammatory, and immune systems. At the cellular level, ...

As the key enzyme in heme degradation, heme oxygenase activity governs cellular heme concentration. Heme oxygenase catalyzes the conversion of heme to carbon monoxide and bilirubin with the release of iron, which can drive the synthesis of ferritin for iron sequestration (1,2). This is the ma ...

Major aspects of renal function such as glomerular filtration, blood flow autoregulation, tubular reabsorption, and medullary concentrating ability rely on an exquisite paracrine-autocrine control of renal microvascular resistances, and on the coordinated network beha ...

As originally described by Golgi, one consistent anatomical feature of all mammalian and many vertebrate kidneys is that a segment of the distal tubule is firmly attached to the vascular pole of its own glomerulum (1). This attachment is formed early in development, and is maintained throughout ...

In vitro microperfusion was developed in order to study the transport of solutes and water across nephrons (1,2). The approach was later extended to renal microvessels for the purpose of measuring vasomotion of glomerular arterioles (3). The purpose of this chapter is to provide a general desc ...

The advent of the technique of the isolated perfused tubule allowed renal physiologists to examine the transport characteristics of all portions of the nephron for the first time. The understanding of renal function prior to the advent of in vitro microperfusion rested on the integrative u ...

Clinical research, like all research, stems from curiosity. Although some research questions are harder to answer than others, the application of a well-designed trial coupled with the right question can yield valuable information. Indeed, a poorly designed randomized trial will not g ...

Bacon’s idealistic description of a research process, as naive and utopian as it sounds today, actually depicts the many functions of a single investigator, from literature search and collection of data to attempts of summing-up the investigation: the merchant, the miner, the depredator and ...

Type 2 diabetes (T2D) is one of the fastest growing threats to human health in westernised and developing countries and is associated with central obesity, atherosclerosis, dyslipidaemia, hyperinsulinaemia and hypertension. Insulin resistance, defined as a diminished response ...