ISSN:1094-5458    

DOI:10.1089/rej.1.1998.1.1

年代:1998

数据来源: MAL

ISSN:1094-5458    

DOI:10.1089/rej.1.1998.1.3

年代:1998

数据来源: MAL

ISSN:1094-5458    

DOI:10.1089/rej.1.1998.1.5

年代:1998

数据来源: MAL

摘要:

During childhood and early adult life, growth hormone (GH), secreted by the anterior pituitary, is involved in the growth of bones and muscles and other organs as well. Aging is characterized by a decrease in muscle mass and bone strength and an increase in adipose, similar to the effects of pathological hyposecretion of GH in the young. Aging is also accompanied by a gradual decrease in the output of GH, like the drying of an internal fountain, until in the eighth decade of life, it is secreted at less than one-fifth of the "youthful" level.The GH hypothesis of aging posits that with the availability of human recombinant growth hormone and human recombinant insulin-like growth factor-I, which mediates most of the effects of GH, the GH hypothesis has become testable. Initial experiments involving short term administration of GH in a group of elderly men did indeed show modest improvement in lean body mass and adipose tissue. These studies are sometimes—and incorrectly—taken as proof of the correctness of the growth hormone hypothesis of aging. Subsequent year-long studies have shown GH therapy causes significant adverse effects. Other concerns of long-term treatment include possible diabetogenic effects, potential for increased risk of cancer, and high costs (>$10,000/yr). IGF-I, which mediates most of the effects of GH, is also being explored experimentally, but its role as a growth factor raises fears about tumor induction.Methods being explored to raise GH levels more physiologically include: GHRH, the GH— releasing hormone produced by the hypothalamus; GH-releasing hexapeptides (GHRPs) which stimulate GH secretion via a novel receptor whose normal function is unknown; and orally active aromatic compounds, developed synthetically which mimic the effects of GHRPs. Because of the unknown long-term effects of elevated GH in the elderly, mimetics should be carefully restricted to clinical trials and temporary

ISSN:1094-5458    

DOI:10.1089/rej.1.1998.1.9

年代:1998

数据来源: MAL

摘要:

The Senescence-Accelerated Mouse (SAM) strain was established in the Department of Senescence Biology, Chest Disease Research Institute, Kyoto University, as a novel murine model of senescence acceleration and age-associated disorders. This strain is actually a group of related inbred strains (recombinant inbred strain-like) including nine strains of accelerated senescence-prone, short-lived mice (SAMP) and three strains of accelerated senescence-resistant, long-lived mice (SAMR). Each SAMP strain shows relatively strain-specific age-associated pathologies. These characteristic pathological phenotypes are similar to those often observed in elder humans. They include senile osteoporosis, osteoarthritis, age-related deficits in learning and memory with/without forebrain atrophy, presbycusis, senile amyloidosis, age-related impairment of the immune response, and so on. The common aging characteristic of SAMP strains is senescence acceleration after normal development and maturation. We have made attempts to intervene the senescence acceleration and specifically in these pathologies: senile osteoporosis and the age-related deficits in learning and memory. These attempts, including caloric restriction, administration of nutrients, chemicals and traditional herbal medicines, show beneficial effects on the aging process of these mice. Similar interventions may prevent or control the onset and progress of age-associated disorders in other species and may have clinical relevance for humans.

ISSN:1094-5458    

DOI:10.1089/rej.1.1998.1.27

年代:1998

数据来源: MAL

摘要:

To date, although the mean human life span has been quite alterable, the maximum human life span has not. Recent work demonstrates that the maximum healthy life span of several species can be extended by dietary restriction and genetic alteration; potentially the maximum healthy human life span might be extended in a similar fashion. More dramatically, researchers have now shown that cell senescence can be reversed by transfection of the catalytic component of telomerase in normal human cells. This allows us to test the hypothesis that cell senescence underlies human aging and age-related disease. This possibility has unprecedented and profound implications for clinical medicine; it has equally unprecedented and profound—and largely unpredictable—implications for our social structures as w

ISSN:1094-5458    

DOI:10.1089/rej.1.1998.1.39

年代:1998

数据来源: MAL

摘要:

Recently, there has been an increased incidence of diabetes mellitus in Japan, where the rate of stroke is high. We reviewed the risk factors of stroke with special reference to "Syndrome X." We reviewed a population-based cohort from 1989 through 1991 that consisted of 7,456 subjects over the age of 35 at Akita, a stroke-prevalent rural district in the northeastern part of Japan known to have the shortest longevity and the highest alcohol consumption in the country. Baseline data were obtained by a questionnaire, physical exams, and blood serum tests. Physical characteristics were similar to national norms, although the proportion of heavy (ex-)drinkers was higher (72.5% for male; 12.0% for female). The prevalence of diabetes mellitus, hypertension, and Syndrome X (defined as diabetes mellitus plus hypertension) was 3.0%, 47.0%, and 1.9%. Observed prevalence of Syndrome X was higher than the expected value. The tendency to disease-clustering was strong in young females. The risk factors of Syndrome X were high body mass index (BMI); a family history of diabetes, hypertension or Syndrome X; regular drinking; high serum GOT; and less walking activity (odds ratio: 1.15, 3.91, 1.62, 4.76, 1.35, 3.97, and 1.21). Stressful occupational environment, feelings of daily stress, a tendency to get angry, and snoring also increased risk of Syndrome X. By 1995,129 stroke cases were observed in the cohort; 123 cases were the first episode. Diabetes mellitus, hypertension, Syndrome X, high BMI, high serum GOT, and less walking activity were associated with significantly higher relative risks for stroke (odds ratio: 2.87, 3.78, 7.42, 1.07, 4.00, and 1.28). Intake of salty foods and hypercholesterolemia were not associated with a higher incidence. The population-attributable risks of stroke related to diabetes mellitus, hypertension, Syndrome X, and high serum GOT were 5.2%, 56.7%, 10.6%, and 7.8%. Syndrome X proved to have the highest relative risk of stroke. Important and controllable risk factors of Syndrome X and stroke were habitual alcohol intake with high serum GOT and less walking activity. Genetic factors were also presumably important to the prevention of Syndrome X. These factors must be considered in strategies aimed at preventing cerebrovascular aging.

ISSN:1094-5458    

DOI:10.1089/rej.1.1998.1.45

年代:1998

数据来源: MAL

摘要:

Most phenotypes of aging in vertebrates may be caused by a progressive decline in the ability of antioxidant defences to maintain cellular and systemic homeostasis. This is due both to a diminished efficacy of those defences and to an enhanced level of pro-oxidant toxicity; the imbalance between the two has been termedoxidative stress.However, the cause of this increasing imbalance remains obscure. This article proposes a mechanism by which spontaneously mutant mitochondrial DNA (mtDNA), despite being present only in very small quantities in the body, may be the main generator of oxidative stress. Mutant mtDNA is distributed very unevenly within a tissue: some cells apparently contain no wild-type mtDNA whatever. Those cells must rely on glycolysis for ATP production; furthermore, they require a system to stabilize their NAD+/NADH ratio. This can only be achieved by an efflux of electrons from the cell, most probably mediated by the plasma membrane oxidoreductase (PMOR). It is proposed that the required rate of electron efflux from these anaerobic cells exceeds the local electron-accepting capacity of "safe" acceptors in plasma such as dehydroascorbate, with the result that reactive species, such as Superoxide, are formed. This leads to increased oxidation of lipids in the plasma, notably of low-density lipoprotein (LDL) particles, which are subsequently imported into mitochondrially healthy cells. This oxidized lipoprotein must be destroyed by the recipient cells' antioxidant defences. That task diverts the cell from the degradation of pro-oxidants that it is itself generating; thus, it imposes oxidative stress on the cell. As the number of anaerobic cells in the body rises, so does oxidative stress in all cells. The consistency of this hypothesis with known facts is discussed, and technically feasible tests are suggested both of the proposed mechanism and of its overall contribution to mammalian aging, including plausible interventions to retard the process.

ISSN:1094-5458    

DOI:10.1089/rej.1.1998.1.53

年代:1998

数据来源: MAL

摘要:

Editor's Note: The question of the technical feasibility of extending the human life span spawns the additional question of the social implications of such extension. John Petersen, president of The Arlington Institute, shapes the answer to this latter question in terms of the cost of such longevity therapy, exploring the outcomes dependent on this variable, then explores the global implications. This effort—which many will consider premature—should be considered the basis for inspiring further, more-detailed efforts to anticipate the social forces which a significant increase in the human life span will bring into motion and their consequent outco

ISSN:1094-5458    

DOI:10.1089/rej.1.1998.1.67

年代:1998

数据来源: MAL

ISSN:1094-5458    

DOI:10.1089/rej.1.1998.1.71

年代:1998

数据来源: MAL