Steven Austad

University of Alabama at Birmingham | UAB · The Graduate School

Barbi et al (Reports, 29 June 2018, p. 1459) reported that human mortality rate reached a "plateau" after the age of 105, suggesting there may be no limit to human longevity. We show, using their data, that potential lifespans cannot increase much beyond the current 122 years unless future biomedical advances alter the intrinsic rate of human aging...

The freshwater cnidarian polyp named Hydra, which can be mass-cultured in the laboratory, is characterized by a highly dynamic homeostasis with a continuous self-renewal of its three adult stem cell populations, the epithelial stem cells from the epidermis, the epithelial stem cells from the gastrodermis, and the multipotent interstitial stem cells...

Aging underlies all the major causes of death and disability in humans. Over the past two decades, basic researchers have been remarkably successful in identifying the underlying processes of aging, and by modifying those processes have discovered multiple methods of extending life and preserving health in experimental laboratory animals. Although...

Women live longer than men in virtually all places and at virtually all times. Often, if not always, women suffer more functional limitations and illnesses than men, however. This has been called the mortality-morbidity paradox. Common laboratory animal species from small roundworms to mice have been used historically to dissect general underlying...

Sex or gender is an important determinant of aging outcomes. However, the role of sex or gender is not well-understood as it represents both distinct biological and social differences in life circumstances. Within human populations, a widely accepted generalization is that men have higher mortality while women have worse health; however, researcher...

When the history of the basic aging research leading to medical treatments that extend human health is written, a significant milestone is likely to be the 1996 paper by Brown-Borg, Borg, Meliska, and Bartke describing the first single gene mutant that extended life in a mammal. Previous research beginning in the late 1980’s had found such genes in...

As primates, humans differ importantly from the great apes and other species in body, brain, and other life history traits. In these allometric traits, larger species mature later, reproduce more slowly, and live longer compared with smaller species. The mechanisms underlying these relationships remain intriguingly obscure. While hypotheses attribu...

Aging is not a disease. It is a generalized and progressive loss of function with the passage of time that makes us increasingly vulnerable to a broad suite of diseases. The Geroscience Hypothesis asserts that any intervention that retards the aging process will simultaneously delay the onset of multiple diseases. Retarding the aging process is not...

Background: Comparative aging studies, particularly those that include species of exceptional resistance to aging processes, can potentially illuminate novel senescence-retarding mechanisms. In recent years, protein homeostasis (proteostasis) has been implicated in fundamental aging processes. Here we further evaluate the relationship between prot...

Raw data for Figs 1–3. Species are Ruditapes = Ruditapes phillipanarum, Callista = Callista chione, Mercenaria = Mercenaria mercenaria, Arctica = Arctica islandica. (XLSX)

One of the biggest challenges to studying causes and effects of aging is identifying changes in cells that are related to senescence instead of simply the passing of chronological time. We investigated two populations of the longest living non-colonial metazoan, Arctica islandica, with lifespans that differed sixfolds. Of four investigated paramete...

A robust, often underappreciated, feature of human biology is that women live longer than men not just in technologically advanced, low-mortality countries such as those in Europe or North America, but across low- and high-mortality countries of the modern world as well as through history. Women's survival advantage is not due to protection from on...

Dakota USA 1 REVIEW Aging and energetics' 'Top 40' future research opportunities 2010-2013 [v1; ref status: indexed, Abstract : As part of a coordinated effort to expand our research activity at Background the interface of Aging and Energetics a team of investigators at The University of Alabama at Birmingham systematically assayed and catalogued t...

The cnidarian Hydra polyps escape senescence, most likely due to the robust activity of their three stem cell populations. These stem cells continuously self-renew in the body column and differentiate at the extremities following a tightly coordinated spatial pattern. Paul Brien showed in 1953 that in one particular species Hydra oligactis cold-dep...

Binding of insulin receptor substrate proteins 1 and 2 (IRS1/2) to the insulin receptor (IR) is essential for the regulation of insulin sensitivity and energy homeostasis. However, the mechanism of IRS1/2 recruitment to the IR remains elusive. Here, we identify adaptor protein APPL1 as a critical molecule that promotes IRS1/2-IR interaction. APPL1...

Bivalve mollusks have several unique traits, including some species with exceptionally long lives, others with very short lives, and the ability to determine the age of any individual from growth rings in the shell. Exceptionally long-lived species are seldom studied yet have the potential to be particularly informative with respect to senescence-r...

Target of rapamycin inhibition by rapamycin feeding has previously been shown to extend life in genetically heterogeneous mice. To examine whether it similarly affected mouse health, we fed encapsulated rapamycin or a control diet to C57BL/6Nia mice of both sexes starting at 19 months of age. We performed a range of health assessments 6 and 12 mont...

Comparing biological processes in closely-related species with divergent life spans is a powerful approach to study mechanisms of aging. The oxidative stress hypothesis of aging predicts that longer-lived species would have lower reactive oxygen species (ROS) generation and/or an increased antioxidant capacity resulting in reduced oxidative damage...

Ubiquitously reduced signaling via Methuselah (MTH), a G-protein coupled receptor (GPCR) required for neurosecretion, has previously been reported to extend life and enhance stress resistance in flies. Whether these effects are due to reduced MTH signaling only in specific tissue(s) and through with signaling effects reduced MTH might produce these...

According to previous studies, a low-calorie diet provides health benefits and increases lifespan in mammals, including primates. Yet a long-term investigation in rhesus monkeys finds no effect on longevity. See Letter p.318

The antidiabetic and antiatherosclerotic effects of adiponectin make it a desirable drug target for the treatment of metabolic and cardiovascular diseases. However, the adiponectin-based drug development approach turns out to be difficult due to extremely high serum levels of this adipokine. On the other hand, a significant correlation between adip...

This chapter reviews the copious evidence for the robustness of women's survival advantage, discusses some of the extant evolutionary and mechanistic hypotheses to explain this pattern, and also examines some pragmatic approaches to investigating this issue. The human sex difference in longevity, and possibly aging, may be as robust an aspect of bi...

Twenty-two large shells (>90 mm shell height) from a sample of live collected hard shell clams, Mercenaria mercenaria, from Buzzards Bay, Woods Hole, Cape Cod, MA, were subjected to sclerochronological analysis. Annually resolved growth lines in the hinge region and margin of the shell were identified and counted; the age of the oldest clam shell w...

Bivalve molluscs are newly discovered models of successful aging, and this invertebrate group includes Arctica islandica, with the longest metazoan life span. Despite an increasing biogerontological focus on bivalves, their life history traits in relation to maximum age are not as comprehensively understood as those in vertebrate model aging organi...

Among the notable trends seen in this year's highlights in mammalian aging research is an awakening of interest in the assessment of age-related measures of mouse health in addition to the traditional focus on longevity. One finding of note is that overexpression of telomerase extended life and improved several indices of health in mice that had pr...

This initial chapter introduces those that follow with a summary of the life spans and end of life pathologies of the several species that are included in later chapters. It is not presented as a complete coverage, but rather as background for what follows, as gathered from the literature and personal information. Included here is that information...

The positive interspecific relation between mammalian body size and longevity was described more than a century ago and remains one of the most robust patterns known in the biology of aging. Hypotheses about the role of metabolic rate or relative brain size in explaining this pattern have not been supported by detailed analyses. This pattern may be...

As impressive as the accomplishments of modern molecular biologists have been in finding genetic alterations that lengthen life in short-lived model organisms, they pale in comparison to the remarkable diversity of lifespans produced by evolution. Some animal species are now firmly documented to live for more than four centuries and even some mamma...

Evolutionary senescence theory predicts that genetically isolated populations historically subjected to low rates of environmentally-imposed mortality will ultimately evolve senescence that is retarded in relation to that of populations historically subjected to higher mortality rates. This prediction was evaluated in the field by comparing three g...

The ability to non-invasively monitor stress hormone levels in free-ranging animals could significantly aid in conservation and management efforts. Our objective in this study was to demonstrate the effectiveness of assay of fecal corticoid metabolites in detecting a stress response in cougars (Puma concolor). Fecal samples were collected from 9 ca...

We describe a cost- and time-efficient method for designing new microsatellite markers in any species with substantial genomic DNA sequence data available. Using this technique, we report 14 new polymorphic dinucleotide microsatellite loci isolated from the common marmoset. The relative yield of new polymorphisms was higher with less labor than des...

In this era of genomics and other exciting technical advances, research on the biology of aging is undergoing a renaissance. This report summarizes 10 cutting-edge areas of research covered in symposia that spanned such topics as stem cells, novel vaccine strategies, nutritional sensing, new concepts of Parkinson's disease, high throughput screenin...

Among this year's highlights in vertebrate aging research, we find a study in which, contrary to the oxidative stress hypothesis of aging, reduced expression of a major cellular antioxidant, glutathione peroxidase 4, led to a small increase in mouse lifespan. By contrast, a large comparative proteomic analysis discovered a remarkably robust and pre...

This chapter presents the history of the historical development of vertebrate models. The National Institute on Aging (NIA) has played a pivotal role in the development of animal models for aging. NIA decided to provide only specific pathogen-free (SPF) animals even though this meant that animals coming from the NIA facility would likely get sick u...

From our limited knowledge of comparative mammalian longevity four generalizations may be made: (1) overall, larger mammal species live longer than smaller ones; (2) certain taxonomic groups such as bats and marsupials are exceptions to this body size-longevity relationship; (3) within species, there is suggestive evidence that smaller individuals...

This chapter reviews research undertaken to understand senescence in birds and mammals in the wild. Increasing age-specific mortality in adulthood is widely used as the gold standard of senescence, both in natural and in laboratory populations. Both reproductive and survival senescence can be difficult to detect in the presence of infectious diseas...

The newly developed analytical techniques for reconstructing evolutionary divergence patterns from molecular sequence data, combined with the virtual avalanche of new DNA sequences from a multitude of organisms, has altered traditional views of large-scale phylogenetic relationships within multicellular animals. A clear pattern in comparing life-ex...

Cells, Aging, and Human Disease. By Michael B. Fossel. Oxford University Press, New York, 2004. 503 pp. $69.95, £43. ISBN 0-19-514035-4. Approaching aging from the perspective of senescence at the levels of cells and organs, the author discusses aging diseases in the context of the tissues that they impact.

The strongest evidence in favor of the idea linking early life growth rate and aging comes from the analysis of size and mean life span among dog breeds. The squared correlation coefficient indicates that more than half of the life-span variation among breeds is explained by the factors-virtually all genetic-that modulate interbreed differences in...

Despite their higher metabolic rates and lifetime energy expenditures, birds generally outlive similar-sized mammals even in the wild, often reaching maturity and aging considerably more slowly. Wild populations of many bird species have been monitored for years using banding-and-recapture methods, allowing field ornithologists to document age-rela...

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 av...

Some researchers have speculated that the senescence-retarding effect of caloric restriction on laboratory rodents is an artifact of overfeeding under captive conditions. The argument posits that mice in nature are chronically calorically restricted; therefore, the typical laboratory protocol of restricting animals to 60% of their ad lib food intak...

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 obta...

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...

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 pa...

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" senescen...

Panel 5 focused on genetic factors that might mediate or moderate the effects of caloric restriction (CR) on longevity. Panel members stated that currently there is limited information directly addressing these issues. Therefore, they focused attention on what studies could be done. In addition, the panel believed that certain conceptual issues mer...

In the field of forensics, scientific experimentation and technological developments can make important contributions in both the prosecution and defense of criminal cases, as Andrew Watson discusses in his News Focus article “A new breed of high-tech detectives” (11 Aug., p. [850][1]). There is

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...

Chance, Development, and Aging. Caleb E. Finch and Thomas B. L. Kirkwood. Oxford University Press, New York, 2000. 288 pp. $35, £24.95. ISBN 0-19-513361-7. Finch and Kirkwood draw on research in developmental biology to argue that random variations in cell fate and function modify genetic and external environmental influences to determine the cour...

To determine the utility of fecal corticosteroid concentration as a measure of chronic stress under laboratory and field conditions, we biochemically and physiologically validated a radioimmunoassay for corticosteroids in three rodent species, house mice (Mus musculus), deer mice (Peromyscus maniculatus), and red-back voles (Clethrionomys gapperi)....

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...

In her commentary (News Focus, 4 June, p. [1607][1]) on an analysis of fractal geometry and allometric scaling (G. B. West et al. , Reports, 4 June, p. 1677), Dana Mackenzie describes how new perspectives in mathematics and biophysics have at last begun to explain “why smaller animals spend life

Most gerontological research using rodent models employs inbred strains, or F1 hybrids derived from them, rather than populations of genetically heterogeneous individuals. This study presents the argument that reliance on genetically homogeneous rodents, though sanctioned by tradition, may not be ideal for many sorts of investigations, and that use...

The authors reply here to comments made by Drs. McClearn and Festing about the strengths and weaknesses of nonstandard mouse models in experimental gerontology, stressing once again the trade-off between internal and external validity. Although the use of genetically isogenic mice may, in some cases, minimize experimental costs by diminishing varia...

Current mechanistic theories of aging would predict that many species of birds, given their unusually high metabolic rates, body temperatures, and blood sugar levels, should age more rapidly than mammals of comparable size. On the contrary, many avion species display unusually long life spans. This finding suggests that cells and tissues from some...

A comparative assessment of aging and longevity in mammals has four uses in aging research. These are: (1) hypothesis formulation and evaluation, (2) investigating the generality of putative aging mechanisms, (3) isolating key physiological factors influencing aging rate, and (4) allowing the most appropriate choice of animal models for particular...

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...

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 r...

SYNOPSIS. The long life spans of birds relative to those of mammals are intriguing to biogerontologists, particularly in light of birds' high body temperatures, high blood glucose levels, and high metabolic rates—all of which should theoretically increase their biochemical liability for rapid aging. The comparative longevity of birds and other flyi...

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...

Sperm precedence, defined as nonrandom differential fertilization success among mating males, is an important postmating component of sexual selection. This study examined the relationship between premating and postmating components of sexual selection in males of the flour beetle (Tribolium castanewn) . Male olfactory attractiveness to females was...

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) nonadapt...

Most gerontologicdl 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 par...

A recent study of seasonal influences on energetics in the southern flying squirrel, Glaucomys volans (Stapp, 1992, Journal of Mammalogy, 73:914-920), compares metabolic and life-history variables in gliding and nongliding arboreal sciurids and interprets them largely in the context of thermoregulatory constraints. We consider an alternative explan...

Initially considered a new species of wild canid when discovered in the mid-1950s, the New Guinea singing dog, also known as Hallstrom's Dog, is more properly considered as a member of the complex of canids including the gray wolf, domestic dog and Australian dingo. The precise taxonomic status and phylogenetic relationships of this group are matte...

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...

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...

Experiments were performed with three dogs, Canis familiaris, trained in human scent discrimination (American Kennel Club utility obedience test), to evaluate whether the dogs could distinguish the scent of their handler from the scent of other humans, irrespective of the body part from which the scent had been collected. The dogs were successful a...