ISSN:1094-5458    

DOI:10.1089/rej.1.1999.2.1

年代:1999

数据来源: MAL

ISSN:1094-5458    

DOI:10.1089/rej.1.1999.2.3

年代:1999

数据来源: MAL

ISSN:1094-5458    

DOI:10.1089/rej.1.1999.2.7

年代:1999

数据来源: MAL

摘要:

Aging is the accumulation of changes that increase the risk of death. The major contributors after age 28 years are the endogenous chemical reactions that, collectively, produce aging changes that exponentially increase the chances for disease and death with age. These reactions constitute the "inborn aging process." This process is the major risk factor for disease and death of the 98% to 99% of cohorts still alive at age 28 in developed countries, where living conditions are now near optimum.The Free Radical Theory of Aging (FRTA) and, simultaneously, the discovery of the ubiquitous, important involvement of endogenous free radical reactions in the metabolism of biologic systems, arose in 1954 from a consideration of aging phenomena from the premise that a single common process, modifiable by genetic and environmental factors, was responsible for the aging and death of all living things. The FRTA postulates that the single common process is the initiation of free radical reactions. These reactions, however initiated, could be responsible for the progressive deterioration of biologic systems with time because of their inherent ability to produce random change. The theory was extended in 1972 with the suggestion that the life span was largely determined by the rate of free radical damage to the mitochondria.The FRTA suggests the possibility that measures to decrease the rate of initiation and/or the chain length of free radical reactions may, at least in some cases, decrease the rate of reactions that produce aging changes without significantly depressing those involved in maintenance and function. Many studies support this possibility.Applications of the FRTA have been fruitful. For example, it is a useful guide to efforts to increase the life span, and it provides plausible explanations for the aging phenomenon (e.g., the association of disease with age as well as insight into pathogenesis; the gender gap; the association between events in early life and late onset disease; and the shortening of telomeres with cell division). Further, it is reasonable to expect on the basis of animal and epidemiologic studies that the increasing population-wide use of antioxidant supplements and ingestion of foods high in antioxidant capacity over the past 40 years have helped to increase the functional life span of the population by contributing significantly to the decline in "free radical" diseases, to increases in the fraction of elderly, and to the decline in chronic disability in this group.

ISSN:1094-5458    

DOI:10.1089/rej.1.1999.2.15

年代:1999

数据来源: MAL

摘要:

We studied age-related changes in the noradrenergic function in the pancreatic islets of streptozotocin diabetic male Wistar rats. Blood glucose, norepinephrine content, noradrenergic receptor binding, and cyclic adenosine monophosphate (cAMP) content were analyzed in the pancreatic islets of these rats. In the present study, the pancreatic islets of diabetic young and old rats showed a significant increase in noradrenaline content accompanied by a significant increase in Bmaxand Kdfor noradrenergic receptors compared with age-matched controls. The cAMP content increased significantly in diabetic young rats, whereas, in old rats a significant decrease was seen when compared with age-matched controls. These data demonstrate that the cAMP system is inhibited in the pancreatic islets of diabetic old rats, whereas it is stimulated in diabetic young rats. This might play a role in the early recovery shown by streptozotocin-treated young rats. Also, changes in the noradrenergic function in the pancreatic islets occurring during aging might account for the increased risk of diabetes mellitus with age.

ISSN:1094-5458    

DOI:10.1089/rej.1.1999.2.37

年代:1999

数据来源: MAL

摘要:

The comparative neurochemical characteristics of brain and liver membranes of senescence-accelerated mice, prone (SAMP1) and senescence-accelerated mice, resistant (SAMR1) strains were evaluated using males and females of several ages. AbnormalN-methyl-D-aspartic acid (NMDA) binding and monoamine oxidase b activity in SAMP brain membranes may promote increased accumulation of reactive oxygen species (ROS) in neurons. Na/K-adinosine triphosphatase (ATPase) and liver cytochrome P450activities are greater in SAMP1 neurons than in SAMR1 neurons, which may reflect an adaptive tissue response to ROS accumulation.

ISSN:1094-5458    

DOI:10.1089/rej.1.1999.2.43

年代:1999

数据来源: MAL

摘要:

A traditional herb ("Toki-shakuyaku-san" or TJ-23) has been reported to cause clinical improvement in patients with Alzheimer's dementia. To investigate possible neuronal mechanisms, we looked at its effect on cholinergic functions in the cortex, hippocampus, striatum, midbrain, pons-medulla oblongata, and cerebellum of rats. In the aged (compared with the adult) rat brain, we found that choline acetyltransferase (CAT) activity was decreased in the cortex and striatum; acetylcholinesterase activity was decreased in the hippocampus, mid-brain and pons-medulla oblongata and increased in the striatum; and muscarinic receptor binding was increased in the cortex and striatum. In the striatum of aged rats, TJ-23 resulted in increased choline acetyltransferase activity, muscarinic receptor binding, and acetylcholinesterase activity. TJ-23 has a significant effect on cholinergic function in the striatum of aged rats.

ISSN:1094-5458    

DOI:10.1089/rej.1.1999.2.51

年代:1999

数据来源: MAL

摘要:

We propose a possible mechanism for the telomere shortening signal. The suggested solution of this as yet unsolved enigma—how cell senescence is causally linked to telomere shortening—is based on a "fountain theory" of modulation of eukaryotic gene expression, in which gene expression is modulated by ionic channels of the inner nuclear membrane. These Ca2+and Zn2+channels are opened transiently through the action of a special small nuclear RNA (the fountain RNA or fRNA) on the ionic channels as conformational changes of the fRNA and channel-forming protein occur. Specific Ca2+and Zn2+ion channels allow these ions to pass from the perinuclear lumen to the nucleoplasmic gene surroundings. The resultant change of ionic concentration in close vicinity to certain genes, in turn, will alter some intranuclear processes and properties (e.g., mRNA stability, transcript maturation, chromatin configuration, transcriptional activity, and so forth).Such fRNA-dependent ionic "fountains," may serve as a major mechanism regulating quantitative gene (phenotypic) expression in eukaryotes. We suggest that among metal-activated transcription factors, zinc-finger nuclear proteins evolved, and they are used in the nucleus as an alternative, noncalcium, path of gene-activity modulation, by means of fRNA-dependent channels, increasing the versatility of a fountain sys

ISSN:1094-5458    

DOI:10.1089/rej.1.1999.2.59

年代:1999

数据来源: MAL

ISSN:1094-5458    

DOI:10.1089/rej.1.1999.2.75

年代:1999

数据来源: MAL

ISSN:1094-5458    

DOI:10.1089/rej.1.1999.2.79

年代:1999

数据来源: MAL