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Steven N Austad

Publications and source records attributed to Steven N Austad.

17 recordsLinked to original sources
PubMed2025

A consensus guide to preclinical indirect calorimetry experiments.

Understanding the complex factors influencing mammalian metabolism and body weight homeostasis is a long-standing challenge requiring knowledge of energy intake, absorption and expenditure. Using measurements of respiratory gas exchange, indirect calorimetry can provide non-invasive estimates of whole-body energy expenditure. However, inconsistent measurement units and flawed data normalization methods have slowed progress in this field. This guide aims to establish consensus standards to unify indirect calorimetry experiments and their analysis for more consistent, meaningful and reproducible results. By establishing community-driven standards, we hope to facilitate data comparison across research datasets. This advance will allow the creation of an in-depth, machine-readable data repository built on shared standards. This overdue initiative stands to markedly improve the accuracy and depth of efforts to interrogate mammalian metabolism. Data sharing according to established best practices will also accelerate the translation of basic findings into clinical applications for metabolic diseases afflicting global populations.

Calorimetry, Indirect↗
PubMed2006

Does caloric restriction extend life in wild mice?

To investigate whether mice genetically unaltered by many generations of laboratory selection exhibit similar hormonal and demographic responses to caloric restriction (CR) as laboratory rodents, we performed CR on cohorts of genetically heterogeneous male mice which were grandoffspring of wild-caught ancestors. Although hormonal changes, specifically an increase in corticosterone and decrease in testosterone, mimicked those seen in laboratory-adapted rodents, we found no difference in mean longevity between ad libitum (AL) and CR dietary groups, although a maximum likelihood fitted Gompertz mortality model indicated a significantly shallower slope and higher intercept for the CR group. This result was due to higher mortality in CR animals early in life, but lower mortality late in life. A subset of animals may have exhibited the standard demographic response to CR in that the longest-lived 8.1% of our animals were all from the CR group. Despite the lack of a robust mean longevity difference between groups, we did note a strong anticancer effect of CR as seen in laboratory rodents. Three plausible interpretations of our results are the following: (1) animals not selected under laboratory conditions do not show the typical CR effect; (2) because wild-derived animals eat less when fed AL, our restriction regime was too severe to see the CR effect; or (3) there is genetic variation for the CR effect in wild populations; variants that respond to CR with extended life are inadvertently selected for under conditions of laboratory domestication.

Aging↗
PubMed2006

Why women live longer than men: sex differences in longevity.

Historically, women have lived longer than men in almost every country in the world. A similar pattern of sex differences in longevity is also found in many other species; however, it is not clear if there are more species in which females live longer or vice versa. For virtually all the primary causes of death and at virtually all ages, mortality rates are higher for men. Women do not live longer than men because they age more slowly, but because they are more robust at every age. Paradoxically, although women have lower mortality rates they have higher overall rates of physical illness than do men. Several hypotheses have been proposed for sex differences in longevity, including more active female immune functioning, the protective effect of estrogen, compensatory effects of the second X chromosome, reduction in the activity of growth hormone and the insulin-like growth factor 1 signaling cascade, and the influence of oxidative stress on aging and disease. At present, none of these hypotheses are strongly supported, although weak support is available for the oxidative stress hypothesis. With the advent of more rapid genome sequencing, molecular tools will become available for more species, thus further detailing the causes for the differences in longevity between the sexes.

Animals↗
PubMed2006

Genetic modulation of hormone levels and life span in hybrids between laboratory and wild-derived mice.

Previously we showed that mouse stocks derived from wild-caught progenitors are long-lived relative to genetically heterogeneous mice derived from laboratory-adapted strains. Here we replicate this life-span effect, and show that F2 hybrids between wild-derived and laboratory-derived stocks have intermediate survival patterns. Moreover, wild-derived mice are small, lean, and slow to mature, and have low serum insulin-like growth factor-I (IGF-I) relative to genetically heterogeneous mice. These traits, too, were at intermediate levels in the F2 hybrids. Furthermore, serum IGF-I at 6 months was a significant predictor of life span in two different populations of F2 hybrid mice. Pooling across stocks, life span was negatively correlated with body weight and serum IGF-I levels, and positively correlated with age at vaginal patency and serum leptin levels. Overall, these finding suggest that wild-derived mice harbor alleles that increase longevity, perhaps through effects on growth, maturation, and early-life hormone levels.

Adrenal Cortex Hormones↗
PubMed2005

The eye of the laboratory mouse remains anatomically adapted for natural conditions.

Evolutionary effects of domestication have been demonstrated for several body systems, including the eye, and for several vertebrate species, including the mouse. Given the importance of the laboratory mouse to vision science, we wished to determine whether the anatomical and histological features of the eyes of laboratory mice are distinct from those of their naturally adapted, wild counterparts. We measured dimensions and masses of whole eyes and lenses from a wild population plus three inbred strains (C57BL/6J, NZB/BINJ, and DBA/1J) of the house house, Mus musculus, as well as wild and outbred laboratory-domesticated stock of the deer mouse, Peromyscus maniculatus. Histological preparations from these eyes were used to determine outer nuclear layer thickness, linear density of the ganglion cell layer, and for indirect immunofluorescence evaluation of cone opsin expression. For all of these traits, no statistically significant differences were found between any laboratory strain and its wild counterpart. The evolutionary effects of domestication of mice therefore do not include changes to the eye in any variable measured, supporting the continued use of this animal as a model for a naturally adapted visual system.

Animals↗
PubMed2005

Diverse aging rates in metazoans: targets for functional genomics.

Aging, or senescence, has typically been measured by demographic analysis, which has its merits but is blind to key aspects of functional development and deterioration. If one uses demographic analyses, however, the approach providing most insight is the analysis of age-specific mortality. The continuing increase in DNA sequencing power combined with emerging computational techniques will allow in the near future detailed investigation of mechanisms of aging in diverse species beyond the typical laboratory bestiary. A comparative approach of this sort needs to consider, in addition to simple longevity, the effects of phylogeny and body size on the species in question. Insight may be gained from the study of species exhibiting accelerated aging relative to more "typical" species. These naturally short-lived species, such as several small shrews and marsupials, avoid the worry inherent in "accelerated aging" genotypes of common models, which is that they are only short-lived because of some idiosyncratic pathology unrelated to general aging. A case of special interest that has yet to be seriously investigated is the domestic dog, in which selective breeding has produced phenotypes within the same species that age at two-fold different rates. Exceptionally long-lived species offer exceptional opportunities to discover whether there are few or many ways to create long-lived organisms. Slow-aging species with the most to offer include bats and naked mole-rats. Perhaps no fundamental question in biology is more intriguing that why and how nature has produced such a dazzling array of aging rates. The development of functional genetics over the next several decades promises to lead us toward an answer.

Animals↗
PubMed2005

Cellular replicative capacity correlates primarily with species body mass not longevity.

Although the limited replicative capacity of human fibroblasts in culture is frequently used as a model for aging, a question of major interest is whether the relationship between in vitro fibroblast proliferative capacity and species longevity is primary or secondary to a relationship with species body size. In this report we establish that body mass is the primary correlative of proliferative potential rather than species life-span.

Adolescent↗
PubMed2005

A new field record for bat longevity.

A new longevity record has been established for a free-living bat-41 years for a male Brandt's bat, Myotis brandtii. The exceptional longevity of bats generally, and this species in particular, should make bats of special interest for researchers studying mechanisms of slow aging.

Aging↗
PubMed2004

Ageing studies on bats: a review.

Bat biologists have long known about the exceptional longevity of bats (Order: Chiroptera), which is unusual for mammals of such a small size and a high metabolic rate. Yet relatively few mechanistic studies have focused on this longevity. On average, species of Chiroptera live three times longer than predicted by their body size. In addition, bats have other life history traits that are characteristic of large, long-lived mammals such as few and large offspring and slow growth rates. Bats fit the evolutionary theory of ageing, as their extended longevity is predicted by their ability to escape extrinsic mortality through flight and, in some species, hibernation. They also show tradeoffs between longevity and reproduction, as predicted by the disposable soma theory of ageing. From a physiological perspective, bat longevity reportedly correlates with replicative longevity, low brain calpain activity, and reduced reactive oxygen species production. As long-lived and physiologically interesting organisms, bats may prove to be an informative model system for ageing research.

Age Factors↗
PubMed2004

Is aging programed?

Development and morphogenesis may easily be thought of as programed, in the sense that they result from a sequence of cellular and molecular events designed by natural selection to produce a given adult phenotype. Aging, except in exceptional cases such as the rapid decay and death of Pacific salmon, is not design but decay. The decay of senescence is not due to natural selection's designing hand, but to its absence. The empirical difference between programed and nonprogramed senescence becomes evident when comparing the stereotypical steps leading to death in salmon contrasted with the lack of such stereotypy in most organisms such as humans and mice. Understanding the distinction between programed development and nonprogramed senescence helps focus attention on the phenotypic performance of adults, which is the focus of natural selection, and therefore be attentive to any unwanted pleiotropic side-effects of genetic or environmental treatments which retard aging.

Aging↗
PubMed2003

Are mice calorically restricted in nature?

An important question about traditional caloric restriction (CR) experiments on laboratory mice is how food intake in the laboratory compares with that of wild mice in nature. Such knowledge would allow us to distinguish between two opposing views of the anti-aging effect of CR--whether CR represents, in laboratory animals, a return to a more normal level of food intake, compared with excess food consumption typical of laboratory conditions or whether CR represents restriction below that of animals living in nature, i.e. the conditions under which house mice evolved. To address this issue, we compared energy use of three mouse genotypes: (1) laboratory-selected mouse strains (= laboratory mice), (2) house mice that were four generations or fewer removed from the wild (= wild-derived mice) and (3) mice living in nature (= wild mice). We found, after correcting for body mass, that ad libitum fed laboratory mice eat no more than wild mice. In fact, under demanding natural conditions, wild mice eat even more than ad libitum fed laboratory mice. Laboratory mice do, however, eat more than wild-derived mice housed in similar captive conditions. Therefore, laboratory mice have been selected during the course of domestication for increased food intake compared with captive wild mice, but they are not particularly gluttonous compared with wild mice in nature. We conclude that CR experiments do in fact restrict energy consumption beyond that typically experienced by mice in nature. Therefore, the retarded aging observed with CR is not due to eliminating the detrimental effects of overeating.

Age Factors↗
PubMed2002

Longer life spans and delayed maturation in wild-derived mice.

Nearly all the experimental mice used in aging research are derived from lineages that have been selected for many generations for adaptation to laboratory breeding conditions and are subsequently inbred. To see if inbreeding and laboratory adaptation might have altered the frequencies of genes that influence life span, we have developed three lines of mice (Idaho [Id], Pohnpei [Po], and Majuro [Ma]) from wild-trapped progenitors, and have compared them with a genetically heterogeneous mouse stock (DC) representative of the laboratory-adapted gene pool. Mean life span of the Id stock exceeded that of the DC stock by 24% (P < 0.00002), and maximal life span, estimated as mean longevity of the longest-lived 10% of the mice, was also increased by 16% (P < 0.003). Mice of the Ma stock also had a significantly longer maximal longevity than DC mice (9%, P = 0.04). The longest-lived Id mouse died at the age of 1450 days, which appears to exceed the previous longevity record for fully fed, non-mutant mice. The life table of the Po mice resembled that of the DC controls. Ma and Id mice differ from DC mice in several respects: both are shorter and lighter, and females of both stocks, particularly Id, are much slower to reach sexual maturity. As young adults, Id mice have lower levels of insulin-like growth factor 1 (IGF-I), leptin, and glycosylated hemoglobin compared with DC controls, implicating several biochemical pathways as potential longevity mediators. The results support the idea that inadvertent selection for rapid maturation and large body size during the adaptation of the common stocks of laboratory mice may have forced the loss of natural alleles that retard the aging process. Genes present in the Id and Ma stocks may be valuable tools for the analysis of the physiology and biochemistry of aging in mice.

Animals↗