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S N Austad

Publications and source records attributed to S N Austad.

At least 19 recordsLinked to original sources
PubMed2001

A reliable assessment of 8-oxo-2-deoxyguanosine levels in nuclear and mitochondrial DNA using the sodium iodide method to isolate DNA.

A major controversy in the area of DNA biochemistry concerns the actual in vivo levels of oxidative damage in DNA. We show here that 8-oxo-2-deoxyguanosine (oxo8dG) generation during DNA isolation is eliminated using the sodium iodide (NaI) isolation method and that the level of oxo8dG in nuclear DNA (nDNA) is almost one-hundredth of the level obtained using the classical phenol method. We found using NaI that the ratio of oxo8dG/10(5 )deoxyguanosine (dG) in nDNA isolated from mouse tissues ranged from 0.032 +/- 0.002 for liver to 0.015 +/- 0.003 for brain. We observed a significant increase (10-fold) in oxo8dG in nDNA isolated from liver tissue after 2 Gy of gamma-irradiation when NaI was used to isolate DNA. The turnover of oxo8dG in nDNA was rapid, e.g. disappearance of oxo8dG in the mouse liver in vivo after gamma-irradiation had a half-life of 11 min. The levels of oxo8dG in mitochondrial DNA isolated from liver, heart and brain were 6-, 16- and 23-fold higher than nDNA from these tissues. Thus, our results showed that the steady-state levels of oxo8dG in mouse tissues range from 180 to 360 lesions in the nuclear genome and from one to two lesions in 100 mitochondrial genomes.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2001

Effect of capture and season on fecal glucocorticoid levels in deer mice (Peromyscus maniculatus) and red-backed voles (Clethrionomys gapperi).

The effect of confinement and season on fecal glucocorticoid (GC) levels in deer mice (Peromyscus maniculatus) and red-backed voles (Clethrionomys gapperi) was determined. Deer mice confined in a Sherman trap more than 4 h had fecal GC levels that were significantly higher than those in individuals that remained in a trap 4 h or less. However, this treatment may not be stressful for red-backed voles as neither plasma nor fecal GC levels were significantly elevated after 12 h of confinement. In addition, a clear temporal pattern in the secretion of fecal GCs was observed between mid June and early November in both species.

Animals↗
PubMed2001

History and prospects: symposium on organisms with slow aging.

We discuss the background concepts which lead to this issue of Experimental Gerontology. On one hand, genetic and molecular studies of short-lived worms, flies, and mice are yielding remarkable discoveries on gene systems that regulate the life span. On the other hand, little is known about the nature of aging in other vertebrates, with life spans extending into the human range or beyond the record 122y human life span, which may have aging processes that are so slow as to be 'negligible'. We point out that organisms with these vastly different life spans have essentially identical cells within an evolutionary group and that the cellular tool kit that existed by 600 million years ago allowed the evolution of life spans ranging up to one million-fold difference in length. The possibility of negligible senescence has not been widely discussed, and may be in conflict with mathematical deductions from population genetics theory. We propose minimal criteria for the lack of senescence: (1) no observable increase in age-specific mortality rate or decrease in reproduction rate after sexual maturity; and (2) no observable age-related decline in physiological capacity or disease resistance. We also introduce some of the species discussed in subsequent chapters which are unfamiliar models to most biomedical researchers.

Aging↗
PubMed2001

An experimental paradigm for the study of slowly aging organisms.

An experimental paradigm for the study of mechanisms of resistance to aging in long-lived organisms has been developed. The paradigm assumes, in concert with accumulating empirical data, that resistance to the aging processes at the organismal level will be reflected in resistance to various stressors at the cellular level. The advantage of this paradigm is that it requires neither the long-term monitoring of individuals nor the use of exceptionally old individuals. The research approach consists of: (1) verifying that primary cell cultures from the long-lived organism exhibit better resistance to key stressors than cells from related, short-lived organisms; (2) assessing differences in gene-expression before and after stress exposure in cultured cells from the long- and short-lived species in order to identify key genes involved in the stress-resistance response; (3) transfecting putative key genes from long-lived species into cells or cell lines of defined stress-resistance and hope to observe that the stress-resistance phenotype has thereby been transferred with the gene(s); (4) generating transgenic model animals containing the gene(s) of interest and look for extended life/health span.

Aging↗
PubMed2001

Comparative biology of aging in birds: an update.

The long life spans and slow aging rates of birds relative to mammals are paradoxical in view of birds' high metabolic rates, body temperatures and blood glucose levels, all of which are predicted to be liabilities by current biochemical theories of aging. Available avian life-table data show that most birds undergo rapid to slow "gradual" senescence. Some seabird species exhibit extremely slow age-related declines in both survival and reproductive output, and even increase reproductive success as they get older. Slow avian senescence is thought to be coupled evolutionarily with delayed maturity and low annual fecundity. Recent research in our lab and others supports the hypothesis that birds have special adaptations for preventing age-related tissue damage caused by reactive oxygen species (ROS) and advanced glycosylation endproducts, or AGEs, as well as an unusual capacity for neurogeneration in brain. Much of this work is in its early stages, however, and reliable biomarkers for comparing avian and mammalian aging need more thorough development.

Aging↗
PubMed2001

Exceptional cellular resistance to oxidative damage in long-lived birds requires active gene expression.

Previous studies indicated that renal tubular epithelial cells from some long-lived avian species exhibit robust and/or unique protective mechanisms against oxidative stress relative to murine cells. Here we extend these studies to investigate the response of primary embryonic fibroblast-like cells to oxidative challenge in long- and short-lived avian species (budgerigar, Melopsittacus undulatus, longevity up to 20 years, vs Japanese quail, Coturnix coturnix japonica, longevity up to 5 years) and short- and long-lived mammalian species (house mouse, Mus musculus, longevity up to 4 years vs humans, Homo sapiens, longevity up to 122 years). Under the conditions of our assay, the oxidative-damage resistance phenotype appears to be associated with exceptional longevity in avian species, but not in mammals. Furthermore, the extreme oxidative damage resistance phenotype observed in a long-lived bird requires active gene transcription and translation, suggesting that specific gene products may have evolved in long-lived birds to facilitate resistance to oxidative stress.

Aging↗
PubMed2000

Why do we age?

The evolutionary theory of ageing explains why ageing occurs, giving valuable insight into the mechanisms underlying the complex cellular and molecular changes that contribute to senescence. Such understanding also helps to clarify how the genome shapes the ageing process, thereby aiding the study of the genetic factors that influence longevity and age-associated diseases.

Aging↗
PubMed1996

Genetic analysis of ageing: role of oxidative damage and environmental stresses.

Evolutionary theory predicts substantial interspecific and intraspecific differences in the proximal mechanisms of ageing. Our goal here is to seek evidence for common ('public') mechanisms among diverse organisms amenable to genetic analysis. Oxidative damage is a candidate for such a public mechanism of ageing. Long-lived strains are relatively resistant to different environmental stresses. The extent to which these stresses produce oxidative damage remains to be established.

Aging↗
PubMed1996

The evolution of the antiaging action of dietary restriction: a hypothesis.

Reducing the intake of dietary energy by laboratory rodents to well below that of animals allowed to eat ad libitum slows the rate of aging. This phenomenon, which is robust and reproducible, is known as the antiaging action of dietary restriction (DR). We hypothesize that this DR response arose because of its evolutionary advantage with respect to survival during periods of unpredictable, short-term food shortage. In our evolutionary scenario, food shortage led to an adaptive redirection of resources away from reproduction toward somatic maintenance via an enhanced heat shock protein response in invertebrates. In vertebrates, an additional involvement of the hypothalamic-adenohypophyseal-adrenal glucocorticoid system was necessitated to protect against excessive systemic defense responses. We suggest several general implications of our hypothesis.

Aging↗
PubMed1995

Birds as animal models for the comparative biology of aging: a prospectus.

Bird species are dramatically longer-lived than similar-sized mammals, in spite of two traits--high metabolic rate and elevated blood glucose--which some modern theories of aging suggest should be associated with accelerated senescence. As a consequence of their longevity, birds may possess specialized protective mechanisms against free radical and Maillard reaction damage, and may offer insight into medical interventions for retarding aging. In this review we have highlighted a number of bird species which are commercially available, easily maintained, and more thoroughly characterized with respect to basic physiology than many biogerontologists realize. There seem to us to be few intrinsic barriers to the development of several avian "mice"--extensively characterized species exhibiting exceptionally long life and retarded aging--and for these to become readily accessible as a laboratory resource for the gerontological research community.

Aging↗
PubMed1994

Selecting animal models of human aging: inbred strains often exhibit less biological uniformity than F1 hybrids.

Most gerontological research is conducted using inbred strains of animals in an attempt to maximize phenotypic uniformity within experiments and thus increase the experimenter's statistical power to detect treatment effects. However, for a wide range of phenotypic traits, F1 hybrids between inbred strains are considerably less variable than the parental inbred strains themselves. Therefore, the use of F1 hybrids is preferable for many research applications. In this article, we discuss the sources of phenotypic variability and explain why F1 hybrids are often less variable than inbred strains; we review the empirical literature illustrating the large range of species and traits for which this is true; and finally we suggest how this finding suggests that F1 hybrids may often be superior animal models for studying the aging process and how to manipulate it.

Aging↗
PubMed1993

FRAR course on laboratory approaches to aging. The comparative perspective and choice of animal models in aging research.

The comparative perspective may be defined as the assumption that individual species or populations differ from one another in potentially instructive ways, and that an appropriate analysis of the nature and magnitude of these differences will yield insights into fundamental processes of aging. Modern experimental research on aging has largely lost its comparative focus, and virtually all research on mammals utilizes inbred strains of laboratory rats and mice, two closely related species chosen not for their properties vis à vis aging, but for convenience. In fact, from a mammalian life history perspective, humans are at the opposite end of the aging continuum than these animal models and other small species conducive to laboratory research, mimic human life history much better. The comparative perspective may play four roles in aging research: 1) hypothesis formulation and evaluation; 2) assessing the generality of aging mechanisms, typically requiring a choice of several animal models distantly related to one another; 3) isolation of key factors influencing aging rate, requiring model systems as closely-related to one another as possible, but differing with respect to aging rate (intraspecific variation in aging rate is particularly useful here); 4) choosing of animal models with particular properties in mind, such as the spectacularly effective antioxidant systems of bats. Increasing the range of animal models used in aging research will accelerate progress in understanding and perhaps manipulating human aging.

Aging↗
PubMed1991

Mammalian aging, metabolism, and ecology: evidence from the bats and marsupials.

This study compared trends in body size, life span, metabolic rate, and ecology of bats and marsupials with those from mammals generally, using a 580 species data base. The linear logarithmic relationship between mammalian body mass and maximum longevity, deleting bats and marsupials, is used as a standard against which to measure life spans of particular mammal groups. Bats have maximum life spans a minimum of 3 times those of nonflying eutherians--a trend resulting from neither low basal metabolic rate, the ability to enter torpor, nor large relative brain size. Marsupials live about 80% as long as nonflying eutherians despite averaging lower basal metabolic rates; similarly, there is no effect of heterothermy or relative brain size. These results directly conflict with predictions of both "rate of living" and brain-size mediated theories of aging. However, they are consistent with an evolutionary theory that posits exceptionally long life spans among mammals with reduced environmental vulnerability.

Aging↗
PubMed1989

Life extension by dietary restriction in the bowl and doily spider, Frontinella pyramitela.

Longevity of free-living female adult bowl and doily spiders was compared with that of captive spiders fed at dietary regimes of one, three, and five Drosophila melanogaster per week. Adult females lived, on average, only 8 days in the field and the pattern of survivorship showed no evidence that senescence contributed to mortality. In the laboratory, mean adult life span was 81.3, 63.9, and 42.3 days on the one, three, and five Drosophila diets, respectively. Decreased feeding rate also delayed egg laying and reduced total fecundity. Survival and reproductive patterns indicated the manifestation of spider senescence at all laboratory feeding levels, with a younger onset of senescence at the higher feeding rates.

Animals↗
PubMedDate not supplied

Menopause: an evolutionary perspective.

Evolutionary biologists classify theories of menopause as either: 1) adaptive, suggesting that female reproductive cessation results from its selective advantage, in that the increased risk of personal reproduction late in life makes it biologically more advantageous to rechannel reproductive energy into helping existing descendents, or 2) nonadaptive, indicating menopause is an artifact of the relatively recent dramatic increase in human longevity. With the possible exception of pilot whales, no mammals studied to date are known to commonly exhibit reproductive cessation in nature. To demonstrate adaptive menopause, one would need to establish both that the longevity of preagricultural humans commonly allowed them to exhibit menopause, and that postreproductive females could assist their descendents sufficiently to compensate for the loss of personal reproduction. The data on longevity of preagricultural humans with respect to the adaptive menopause hypothesis are mixed. Evolutionary models evaluated with data from modern hunting-gathering or agricultural humans fail to find that humans can assist their descendents sufficiently to offset the evolutionary cost of ceasing reproduction. However, assuming the human body has been physiologically adapted to the conditions extant during the vast majority of human history, it may be well worth pursuing how the signs and symptoms of menopause are affected by dietary, exercise, and reproductive hormone regimes mimicking those of the late Paleolithic era.

Animals↗