Normal human cells have a finite proliferative potential in vitro. However, some DNA viral proteins, such as SV40 Tg, can alter this and extend the lifespan after which the cells enter crisis, a period when massive cell death occurs. Based on these observations, a two-stage model for cellular senescence has been proposed with a distinct function for each stage.
Aging is characterized by a progressive decline of cellular functions. The aging liver appears to preserve its function relatively well. Aging is associated in human liver with morphological changes such as decrease in size attributable to decreased hepatic blood flow. Ultrastructural analysis of the human liver has revealed that the integrity of mitochondria and enzymatic activity remain mostly unchanged with aging. Reactive oxygen species (ROS) are involved in the aging process and result mainly from nonenzymatic processes in the liver.
The nematode Caenorhabditis elegans is an important model for studying the genetics of ageing, with over 50 life-extension mutations known so far. However, little is known about the pathobiology of ageing in this species, limiting attempts to connect genotype with senescent phenotype. Using ultrastructural analysis and visualization of specific cell types with green fluorescent protein, we examined cell integrity in different tissues as the animal ages.
Caloric restriction (CR) may retard aging processes and extend lifespan in organisms by altering energy-metabolic pathways. In CR rodents, glucose influx into tissues is not reduced, as compared with control animals fed ad libitum (AL), although plasma concentrations of glucose and insulin are lower. Gene expression profiles in rodents have suggested that CR promotes gluconeogenesis and fatty acid biosynthesis in skeletal muscle. In the liver, CR promotes gluconeogenesis but decreases fatty acid synthesis and glycolysis.
For nearly 70 years it has been recognized that reduction in caloric intake by 30-40% from ad libitum levels leads to a significant extension of mean and maximal lifespan in a variety of short-lived species. This effect of caloric restriction (CR) on lifespan has been reported in nearly all species tested and has been reproduced hundreds of times under a variety of different laboratory conditions. In addition to prolonging lifespan, CR also prevents or delays the onset of age-related disease and maintains many physiological functions at more youthful levels.
Studies were conducted to directly test whether the introduction of telomerase protects cancer-prone human mammary epithelial cells from chromosomal instability and spontaneous immortalization. Using a model for Li Fraumeni Syndrome (LFS), infection of human telomerase resulted in maintenance of telomere lengths, extension of in vitro lifespan, and prevention of spontaneous immortalization.
Definitions of psychological abuse are reviewed and a new definition proposed, operationalized as an extension of an existing measure of childhood, the Childhood Experience of Care and Abuse (CECA). This semistructured, investigator-based interview is designed for use with adults to collect retrospective accounts of childhood adverse experience. The CECA extension identifies nine subtypes of psychological abuse, with a single global severity rating.
A new retrospective interview assessment of childhood psychological abuse, an extension to the Childhood Experience of Care and Abuse (CECA) instrument, is described in a companion article (Moran, Bifulco, Ball, Jacobs, & Benaim, 2002). The purpose of the present article is to examine the relationship of childhood psychological abuse to other adverse childhood experiences and to major depression and suicidal behavior in adult life. Childhood experience and lifetime disorder were assessed retrospectively in a high-risk, community series of London women (n = 204).
Numerous studies have shown that supplementation of the growth medium of human fibroblasts with dexamethasone at physiologic concentrations extends replicative lifespan up to 30%. While this extension of lifespan has been used to probe various aspects of the senescent phenotype, no mechanism for the increased lifespan of human fibroblasts grown in the presence of dexamethasone has ever been identified.
The lifespan of human foreskin fibroblasts (HFF5), cultured under standard in vitro conditions (including ambient atmospheric oxygen tension), was extended slightly by expression of exogenous mortalin (mot-2)/mthsp70/Grp75, but not by the catalytic subunit of telomerase, hTERT. Together, mot-2 and hTERT permitted bypass of senescence, a substantial extension of lifespan, and possibly immortalization. This is the first demonstration that mot-2 and telomerase can cooperate in the immortalization process.