The role of dietary carbohydrates in organismal aging

Carbohydrates are essential nutrients that are used as a primary source of energy. Carbohydrate utilization should be properly controlled, as abnormal regulation of carbohydrate metabolism is associated with diseases, such as diabetes, cardiovascular diseases, and stroke. These metabolic syndromes have become a serious problem in developed countries, and there is an increased need for research examining the influence of carbohydrates on animal physiology. Diets enriched in glucose, a major carbohydrate, are also associated with accelerated aging in several model organisms, including yeast and Caenorhabditis elegans (C. elegans). Genetic factors that mediate the effects of high glucose diets on aging have been identified during the last decade, mostly through the use of C. elegans. In this review, we describe studies that determine the effects of carbohydrate-enriched diets on aging by focusing on the mechanisms through which evolutionarily conserved pathways mediate the lifespan-altering effects of glucose in C. elegans. These include the insulin/insulin-like growth factor-1, sterol-regulatory element-binding protein, and AMP-activated protein kinase signaling pathways. We also discuss the effects of various carbohydrates and carbohydrate-derived metabolites on aging in model organisms and cultured mammalian cells. Finally, we discuss how dietary carbohydrates influence health and aging in humans.     

Glucose-6-phosphate dehydrogenase of rat liver peroxisomes

Summary A study was made of the effect of chronic administration of clofibrate on the activity and intracellular localization of rat liver glucose-6-phosphate dehydrogenase. Clofibrate-activated glucose-6-phosphate dehydrogenase was found to be located in peroxisomes.     

The effect of aging on rat liver regeneration

Summary The effect of age on hepatocyte mensuration and mitotic activity 48 h after partial hepatectomy was investigated in rats. Both age and partial hepatectomy had significant effects upon hepatocyte counts per microscopic field. The number of hepatocytes per microscopic field declined with age in the control groups of different advancing ages and in the experimental groups of advancing ages. There was essentially no mitotic activity in the livers of the control groups. However, mitotic counts were greatly increased in livers from those animals that were partially hepatectomized; the increase in mitotic activity in the 13-month-old animals was double over that observed in both the very young and the very old.Acknowledgment. This research was supported in part by an Eastern Virginia Medical School Biomedical Research Development Fund. The investigators acknowledge the Gerontology Research Center, NIA, Baltimore, Maryland for their support.     

The role of repair in radiobiology

Summary Apart from cancer and mutation induction, radiobiological effects on mammals are mostly attributable to cell death, defined as loss of proliferative capacity. Survival curves relate retention of that capacity to radiation dose, and often manifest a quasi-threshold (shoulder). The shoulder is attributable to an initial mechanism of repair (Q-repair) which is gradually depleted as dose increases. Another form of repair, which is not depleted (P-repair), increases the dose required to deliver an average of one lethal event per cell (dose D₀). Neither form of repair can unambiguously be linked with repair of defects in isolated DNA. An important initial lesion may well be disruption of the complex structural relationship between the DNA, nuclear membrane and associated proteins. One form of P-repair may be restoration of that structural relationship.     

The role of repair in radiobiology

Apart from cancer and mutation induction, radiobiological effects on mammals are mostly attributable to cell 'death', defined as loss of proliferative capacity. Survival curves relate retention of that capacity to radiation dose, and often manifest a quasi-threshold ('shoulder'). The shoulder is attributable to an initial mechanism of repair ('Q-repair') which is gradually depleted as dose increases. Another form of repair, which is not depleted ('P-repair'), increases the dose required to deliver an average of one lethal event per cell (dose 'D0'). Neither form of repair can unambiguously be linked with repair of defects in isolated DNA. An important initial lesion may well be disruption of the complex structural relationship between the DNA, nuclear membrane and associated proteins. One form of P-repair may be restoration of that structural relationship.     

The role of thrombospondin-1 in apoptosis

The thrombospondins are a family of extracellular proteins that participate in cell-to-cell and cell-to-matrix communication. They regulate cellular phenotype during tissue genesis and repair. Five family members, each representing a separate gene product, probably exist in most vertebrate species. Like most extracellular proteins, the thrombospondins are composed of several structural domains that are responsible for the numerous biological functions that have been described for this protein family. Considerable progress has been made towards understanding the function of thrombospondins. The role of thrombospondin in the process of apoptosis or programmed cell death has recently come into focus. In this review we will concentrate on the role of thrombospondin-1 in the broad field of apoptotis research. Received 5 December 2001; received after revision 28 March 2002; accepted 28 March 2002     

The role of judgement in macroeconomic forecasting

This paper examines the rationale for, and influence of, judgemental adjustments in macroeconomic forecasting, using two particular forecasts for the UK economy recently published by the National Institute of Economic and Social Research and the London Business School. It is found that in some cases such adjustments have a major effect on the forecasts and can also explain some of the differences in the two rival forecasts. However the number of adjustments for which this is true is not great. An implication of these findings is that, if these forecasts can be regarded as typical, then macroeconomic forecasters should be urged to give a reasonable account of the role of judgemental adjustments in their forecasts, particularly since the amount of information which would be required is not likely to be excessive.     

The role of Epac in the heart

As one of the most important second messengers, 3′,5′-cyclic adenosine monophosphate (cAMP) mediates various extracellular signals including hormones and neurotransmitters, and induces appropriate responses in diverse types of cells. Since cAMP was formerly believed to transmit signals through only two direct target molecules, protein kinase A and the cyclic nucleotide-gated channel, the sensational discovery in 1998 of another novel direct effecter of cAMP [exchange proteins directly activated by cAMP (Epac)] attracted a great deal of scientific interest in cAMP signaling. Numerous studies on Epac have since disclosed its important functions in various tissues in the body. Recently, observations of genetically manipulated mice in various pathogenic models have begun to reveal the in vivo significance of previous in vitro or cellular-level findings. Here, we focused on the function of Epac in the heart. Accumulating evidence has revealed that both Epac1 and Epac2 play important roles in the structure and function of the heart under physiological and pathological conditions. Accordingly, developing the ability to regulate cAMP-mediated signaling through Epac may lead to remarkable new therapies for the treatment of cardiac diseases.     

The role of endosomal-recycling in long-term potentiation

Long-term potentiation (LTP) defines persistent increases in neurotransmission strength at synapses that are triggered by specific patterns of neuronal activity. LTP, the most widely accepted molecular model for learning, is best characterised at glutamatergic synapses on dendritic spines. In this context, LTP involves increases in dendritic spine size and the insertion of glutamate receptors into the post-synaptic spine membrane, which together boost post-synaptic responsiveness to neurotransmitters. In dendrites, the material required for LTP is sourced from an organelle termed the endosomal-recycling compartment (ERC), which is localised to the base of dendritic spines. When LTP is induced, material derived from the recycling compartment, which contains α-amino-3-hydroxy-5-methyl-4-isoxazole propionate-type glutamate receptors (AMPARs), is mobilised into dendritic spines feeding the increased need for receptors and membrane at the spine neck and head. In this review, we discuss the importance of endosomal-recycling and the role of key proteins which control these processes in the context of LTP.     

The role of hypercapnia in acetazolamide teratogenesis

Zusammenfassung Für die teratogene Wirkung von Acetazolamid beim Hamster ist nicht nur der die CO₂-Konzentration erhöhende Effekt verantwortlich. Das Aussetzen der mit Acetazolamid behandelten Muttertiere in eine mit 10% CO₂ angereicherte Atmosphäre erhöhte zwar die Inzidenz, nicht aber den Schweregrad der Missbildungen der Vorderextremität.

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This work was supported by NIH grants No. HD 03298 and GM 00687, and the elective program of the Johns Hopkins University School of Medicine, Baltimore, Maryland. Acetazolamide was kindly supplied by Lederle Laboratories, Pearl River, N. Y.