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PubMed1995

Genes that regulate both development and longevity in Caenorhabditis elegans.

The nematode Caenorhabditis elegans responds to conditions of overcrowding and limited food by arresting development as a dauer larva. Genetic analysis of mutations that alter dauer larva formation (daf mutations) is presented along with an updated genetic pathway for dauer vs. nondauer development. Mutations in the daf-2 and daf-23 genes double adult life span, whereas mutations in four other dauer-constitutive genes positioned in a separate branch of this pathway (daf-1, daf-4, daf-7 and daf-8) do not. The increased life spans are suppressed completely by a daf-16 mutation and partially in a daf-2; daf-18 double mutant. A genetic pathway for determination of adult life span is presented based on the same strains and growth conditions used to characterize Daf phenotypes. Both dauer larva formation and adult life span are affected in daf-2; daf-12 double mutants in an allele-specific manner. Mutations in daf-12 do not extend adult life span, but certain combinations of daf-2 and daf-12 mutant alleles nearly quadruple it. This synergistic effect, which does not equivalently extend the fertile period, is the largest genetic extension of life span yet observed in a metazoan.

Animals↗
PubMed1998

Longevity and gray hair, baldness, facial wrinkles, and arcus senilis in 13,000 men and women: the Copenhagen City Heart Study.

BACKGROUND: We have previously reported that men who look older than their contemporaries have a significantly higher risk for myocardial infarction. The purpose of this study was to investigate whether persons with pronounced aging signs such as graying of hair, baldness, or facial wrinkles are prone to a shorter life span compared to their contemporaries. METHODS: In the Copenhagen City Heart Study comprising a random sample of 20,000 men and women, we also recorded, in addition to cardiovascular risk factors, data on signs of aging: extent of gray hair, baldness, facial wrinkles, and arcus senilis (corneal arcus). During 16 years of follow-up, 3,939 persons (1,656 women and 2,283 men) had died. The Cox regression model for proportional hazards, which included age as an explanatory variable, was used for descriptive analysis of the correlation between these aging signs and all-cause mortality. RESULTS: We found no correlation between the mortality and the extent of graying of the hair, or baldness or facial wrinkles in either of the sexes, irrespective of age. A single exception was observed in a small subgroup of men with no gray hair. They had a slightly, but significantly, lower mortality than the rest [relative risk (RR) = .81, 95% confidence interval (CI) .67-.98; p < .05]. The presence of arcus senilis was significantly correlated with a shorter life span in women (RR = 1.25, 95% CI 1.08-1.46; p < .01). For men the same tendency was found, but the correlation was not statistically significant. CONCLUSION: We conclude that the degrees of graying of the hair, baldness, and facial wrinkles are not predictive of a shorter life span in men and women in the Copenhagen City Heart Study.

Adult↗
PubMed2003

Delayed occurrence of fatal neoplastic diseases in ames dwarf mice: correlation to extended longevity.

Ames dwarf mice have drawn much attention in aging research because of their marked life extension. Studies demonstrate that some of the physiological characteristics of Ames dwarf mice are similar to those of dietary restricted mice. Because dietary restriction has been shown to suppress and/or delay the occurrence of various age-related diseases, we investigated age-related pathological changes in Ames dwarf mice. We observed Ames dwarf mice to have a delayed occurrence of presumably fatal neoplastic disease compared with their normal siblings. In addition to the delayed occurrence, we found that the incidence of presumably fatal adenocarcinoma in lung was significantly lower in Ames dwarf mice than for their normal siblings. The delayed occurrence of total neoplastic lesions and reduced incidence of adenocarcinoma in lung possibly could be attributed to the retardation of tumor development by changes in the levels of growth hormone and insulin-like growth factor-1, and thereby be a major contributing factor to the extended life span observed in these mice.

Adenocarcinoma↗
PubMed2006

Water balance and cation levels in Drosophila: can early physiological decline predict aging and longevity?

Many studies demonstrate changes in physiology, biochemistry, or behavior with age, but almost no studies demonstrate such changes being predictive of aging. We subsampled from 10 genetically distinct strains of Drosophila melanogaster as they aged, at three time points, measuring change over time of parameters related to water balance (water content, desiccation survival, and K(+), Mg(2+), and Ca(2+) levels). We then determined whether the change over time in any parameters is predictive of mean life span or time of onset of aging. We observed a schedule of aging-related changes. Time of onset of aging was negatively correlated with decline in desiccation resistance and with decline in K(+) between days 0 and 15, and was positively correlated with decline in Ca(2+) between days 15 and 24. We suggest that the potassium result, at least, may be due to loss of functional cytoplasm. We also discuss the use of different estimates of aging in the context of this study.

Aging↗

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