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 ...
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 ...
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 ...
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 ...
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 ...
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 ...
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 ...
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- ...
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 ...
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 ...
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 ...
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 ...
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 ...
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 ...