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In recent years the role played by mitochondria in cellular aging has become the focus of intensive research. The concept that these energy-producing organelles are involved in aging derives from the views of Harman (1) and Gerschman (2) linking senescence to the damaging effects of free radic ...

Pentosidine is a highly fluorescent advanced glycation end product (AGE) and crosslink derived from one molecule of arginine and one of lysine bridged in an imidazo-pyridinium structure (Fig. 1). It was first isolated from articular cartilage by Sell and Monnier (1), and has now been detected a ...

It is now recognized that oxidation of low-density lipoprotein (LDL) is a key event in the development of atherosclerosis (1). In vivo, oxidation is believed to occur primarily in the arterial wall. In early atherosclerotic lesions oxidation may be initiated by enzymes, including myeloper ...

The increasing information on the specific DNA sequence alterations that occur in mutated genes of human somatic cells has allowed the establishment of mutational spectra. Endogenous and exogenous exposures as well as individual susceptibility factors seem to contribute to the co ...

Aging is a complex, biological process that is contributed to by intrinsic (genetic) and extrinsic (nutrition, infectious agents, xenobiotic exposure, etc.) factors (1). Several decades ago it was first proposed that instabilities in the organization and expression of the genetic mat ...

8-Oxoguanine is one of the most studied base oxidation products found in DNA. It has potential biological significance, because if present in DNA that is replicating, it can lead to incorporation of adenine rather than cytosine in the daughter strand. Thus it is considered as a premutagenic lesi ...

There is accumulating evidence that oxidative damage to protein, lipid, carbohydrate and DNA is an important cause and/or effect of cellular and subcellular changes associated with disease, and is responsible for at least some of the physiological, but ultimately fatal, changes that acc ...

DNA is the most important target molecule for cell killing or the induction of cellular damage by chemical or physical agents. Cell killing depends on the type and amount of damage induced. Exposure to physical or chemical agents can induce a large variety of lesions in DNA: single- and double-stran ...

A large number of studies indicate that DNA damage and mutation increase with age in human cells and tissues (1). Age-related degenerative disorders in which DNA damage has been invoked include heart disease and neurodegenerative conditions such as Alzheimer’s disease, amyotrophic la ...

The human body is continuously exposed to a wide array of structurally diverse chemicals. Such exposure occurs even at the fetal stage as almost all chemicals that are present in the mother’s blood can readily cross the placenta and reach the fetus. Some of these chemicals are ingested voluntarily, ...

The need to analyze changes in gene expression patterns occuring in senescent cells has stimulated the search for proper methods to identify the actual differences between young and senescent cells. In studies of aging, differential display reverse transcriptase-polymerase cha ...

Most of our models of signal transduction through the T-cell receptor (TCR) involve components and pathways first described in T-cell clones and T-cell lymphomas such as the Jurkat cell line (1). These studies, while providing valuable insights, are not always reliable guides to the analogous ...

Apoptosis describes an intrinsic cell suicide program that may be activated by both endogenous and exogenous stimuli. This method of cell death is characterized by specific morphological features including chromatin condensation, nuclear fragmentation, cell shrinkage, mem ...

Telomere length measurement can be used both to monitor the proliferation of long-term cultures of somatic cells as well as to determine the replicative history of in vivo-derived cells. The most frequently used technique for telomere length measurement is Southern hybridization (1, 4). T ...

Techniques for generating human T-cell clones (TCCs) were first described nearly two decades ago (1, 2). This was a direct consequence of the discovery of T-cell growth factor and the subsequent ability to propagate T-cells over extended periods (3). Early on, numerous publications in immunol ...

In this chapter, we present standard procedures for the culture of human cells that exhibit a finite proliferative capacity (replicative life-span). The use of a cell culture model has the advantage of providing a controlled environment to study a wide variety of cellular phenomena. It also has ...

Enormous advances in our understanding of human aging have occurred during the last 50 yr. From the late 19th to the mid-20th centuries only four comprehensive and important sources of information were available:

The major cause of cystic fibrosis is the presence of processing mutations in CFTR (such as deletion of Phe-508 (F508del-CFTR)) that disrupt folding of the protein and trafficking to the cell surface. Processing mutations appear to inhibit folding of CFTR so that it accumulates in the endoplas ...

Small molecules acting as selective activators (potentiators), inhibitors, or “correctors” of the CFTR chloride channel represent candidate drugs for various pathological conditions including cystic fibrosis and secretory diarrhea. The identification of CFTR pharmac ...

The pilocarpine sweat test, and in vivo assessment of CFTR function via nasal potential difference or intestinal current measurement are important tools to confirm the diagnosis of CF in subjects with suggestive symptoms. Since these tests reflect CFTR function and thus relate to the basic ...