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Caloric restriction remains the only nongenetic intervention that has been consistently and reproducibly shown to extend both average and maximal lifespan in a wide variety of species. If shown to be applicable to human aging, it is unlikely that most people would be able to maintain the 30–40% re ...

Normal human somatic cells undergo limited cell division cycles and enter irreversible replication arrest called senescence. Cellular senescence of many human cell types is regulated by the length and status of telomeric sequences, which is shortened after each round of DNA replicat ...

Cellular senescence is generally defined as an irreversible state of G1 cell cycle arrest in which cells are refractory to growth factor stimulation. Cellular senescence can be induced through several different mechanisms. Primary mammalian cells display a finite life span, sugges ...

Maternal age affects oocyte quality and early embryo development. Aberrant meiosis of oocytes and compromised early embryo development from older females could originate from defects in the nucleus, the cytoplasm, or both. Nuclear transfer has been used for decades as a tool to study nucle ...

Ribozymes are naturally-occurring catalytic RNAs from the viroid world and are being engineered in the laboratory to perform sequence-specific cleavage of a desired mRNA target. Since their Nobel Prize-winning discovery, there has been considerable interest in the utility of ribo ...

The methodology of testing anti-aging drugs in laboratory mice is presented. It includes the selection of mouse strain, sex, age at start of treatment, housing conditions, design of the long-term study, some noninvasive methods of assessment, pathology examination, and statistical tre ...

We developed a high-throughput functional genomic screening system that allows identification of genes prolonging lifespan in the baker’s yeast Saccharomyces cerevisiae. The method is based on isolating yeast mother cells with a higher than average number of cell divisions as indi ...

The aging process encompasses changes at the molecular, cellular, and organismal levels that can be analyzed by a variety of methods. For several decades, a popular mode of studying biological aging has been the analysis of cells cultured in vitro that display cellular senescence. Current in ...

Methods to detect and analyze somatic mutations in higher organisms are critically important in view of their causal role in cancer, heritable diseases, and, possibly, aging. Here, we describe detailed protocols for the use of a mutational reporter system based on lacZ-containing plasmi ...

Analyses of mutations affecting life span in model organisms have revealed a number of genes that regulate longevity in evolutionarily conserved signaling pathways. These studies suggest that genes involved in insulin-like signaling pathways, metabolism, stress response, and ...

Molecular and cellular processes related to the senescence syndrome are determined by programs of differential gene expression. Subtractive cDNA hybridization is a powerful approach to identify and isolate differentially expressed genes in various systems. A highly effecti ...

Understanding the genetic basis of the effects of aging on the decline in the immune response is an enormous undertaking. The most prominent age-related change in the immune system is thymic involution. This chapter will focus on the use of C57BL/6 J X DBA/2 J (BXD) recombinant inbred (RI) strains of mice ...

This chapter describes protocols for two-dimensional (2D) gel electrophoresis (isoelectric focusing followed by sodium-dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis ), staining of gels with the fluorescent dye Sypro Ruby, 2D gel image analysis, peptide mass fin ...

Metabolomics is the systematic and theoretically comprehensive study of the small molecules that comprise a biological sample, e.g., sera or plasma. Metabolomics, in conjunction with other “-omics” approaches, offers a new window onto the study of aging and caloric restriction. Here, we p ...

Most normal human cells undergo cellular senescence after accruing a fixed number of cell divisions, or are challenged by a variety of potentially oncogenic stimuli, in culture and most likely in vivo. Cellular senescence is characterized by an irreversible growth arrest and certain alt ...

Culturing and subcultivation of normal human diploid fibroblasts have advanced our understanding of the molecular events involved in aging. This progress is leading to the development of therapies that slow or ablate the adverse physiological and pathological changes associat ...

Cellular senescence, the ultimate and irreversible loss of replicative capacity of cells in primary culture, has been a popular model for studying the aging process. However, the replicative life span of human fibroblasts is heterogeneous even in clonal populations, with the fraction of ...

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 ...