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Biomarkers and Surrogates in Clinical Studies

Biomarkers are defined as anatomic, physiologic, biochemical, molecular, or genetic parameters associated with the presence, absence, or severity of a disease process. As such, biomarkers may be useful as prognostic and diagnostic tests. Establishing the utility of a given biomarker ...

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Evaluation of Diagnostic Tests

As technology advances, diagnostic tests continue to improve, and each year, we are presented with new alternatives to the standard procedures. Given the plethora of diagnostic alternatives, diagnostic tests must be evaluated to determine their place in the diagnostic armamentari ...

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Analysis of Randomized Controlled Clinical Trials

When analyzing the results of a trial, the primary outcome variable must be kept in clear focus. In the analysis plan, consideration must be given to comparing the characteristics of the subjects, taking account of differences in these characteristics; intention-to-treat analysis; inte ...

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Modeling Longitudinal Data, II: Standard Regression Models and Extensions

In longitudinal studies, the relationship between exposure and disease can be measured once or multiple times while participants are monitored over time. Traditional regression techniques are used to model outcome data when each epidemiological unit is observed once. These models ...

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The Use of Genetically Engineered Mice in Aging Research

The primary model systems used for studying the role of regulated gene expression in senescence and the effects that genetic variations have on this process have been to date either mammalian cells in vitro or invertebrate systems such as yeast, C. elegans, and Drosophila. Both types of model syst ...

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Dietary Restriction and Life-Span Extension

The popularity of the dietary restriction (DR) paradigm (often used interchangeably with calorie restriction) among gerontologists is primarily based on the research finding of the last two decades. Originally discovered by McCay’s group in the 1930s, this paradigm showed that anim ...

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Immunogenetics and Life-Span: HLA

The major histocompatibility complex (MHC) is located in the region 9p216pter on the short arm of chromosome 6 and encompasses approx 4000 kilobases of genomic DNA. Contained within this complex are numerous genes with immune-related functions: notably the class I and class II human leukoc ...

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Age-Related Alterations to Natural Killer Cell Function

Human natural killer (NK) cells represent a heterogeneous lymphoid population involved in the recognition and lysis of tumor and virally infected cells. NK cells are defined by the expression of the IgG Fc receptor CD16 (FcγRIIIA) and/or CD56. NK cells do not rearrange immunoglobulin (Ig) or T- ...

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Dendritic Cells in Old Age

Dendritic cells (DCs) are powerful antigen-presenting cells that have the unique capacity to stimulate naive T-cells (1, 2). DCs are identified by a triad of criteria: Morphologically, they exhibit pronounced cytoplasmic veils that are mobile and can easily be observed under a phase-cont ...

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Assessment of T-Cell Function in the Aged

Certain immunological activities, particularly cell-mediated immunity, decline with advancing age. Gaining insight into the underlying mechanism(s) is complicated by the fact that human T-cells comprise several functionally and phenotypically distinct populations a ...

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Analysis of Mitochondrial DNA Mutations: Point Mutations

Since the first demonstration that mutations of the mitochondrial genome were associated with human disease, more than 100 pathological mitochondrial DNA (mtDNA) defects have been characterized in patients with a broad spectrum of clinical manifestations (1). Single-point mut ...

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Analysis of Mitochondrial DNA Mutations: Deletions

Although the precise mechanisms of the aging process remain poorly understood, a plausible theory for cellular dysfunction and deterioration during aging involves mitochondria (1, 2). The major function of mitochondria is to generate energy for cellular processes in the form of ATP by ox ...

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Causes and Consequences of Damage to Mitochondria: Study of Functional Aspects by Flow Cytometry

A rapidly increasing amount of data supports the view that progressive bioenergetic loss caused by injury of the main energy-producing subcellular organelles, that is, the mitochondria, plays a key role in aging. A link between senescence and energy loss is already implied in Harman’s (1) free ...

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Causes and Consequences of Damage to Mitochondria: Morphological Aspects

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 ...

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Measurement of Pentosidine in Biological Samples

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 ...

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Assessment of Susceptibility of Low-Density Lipoprotein to Oxidation

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 ...

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Somatic Mutations and Aging: Methods for Molecular Analysis of HPRT Mutations

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 ...

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Mutation and the Aging Process: Mutant Frequency at the HPRT Gene Locus as a Function of Age in Humans

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 ...

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Measurement of 8-Oxo-deoxyguanosine in Lymphocytes, Cultured Cells, and Tissue Samples by HPLC with Electrochemical Detection

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 ...

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Assessing Age-Related Changes in Antioxidant Status: The FRASC Assay for Total Antioxidant Power and Ascorbic Acid Concentration in Biological Fluids

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 ...

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