The Endocrine Regulation of Aging by Insulin-like Signals

Tatar, Marc; Bartke, Andrzej; Antebi, Adam

doi:10.1126/science.1081447

Cited by 1,201 publications

(926 citation statements)

References 68 publications

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“…Comparison of longevity-associated genetic alterations in multiple model organisms has frequently implicated the insulin-like growth factor-1 (IGF-1) signaling pathway as a critical player in the control of longevity (Kenyon, 2001;Longo and Finch, 2003). Nematodes and fruit flies with mutations in insulin/IGF-1 signaling pathway members often show dramatically increased longevity (Giannakou and Partridge, 2007;Kenyon, 2001;Tatar, Bartke, and Antebi, 2003). Moreover, mice with defects in growth hormone (GH)/IGF-1 pathway genes exhibit enhanced median and maximal lifespans (Bartke and Brown-Borg, 2004;Kopchick, 2008).…”

Section: Introductionmentioning

confidence: 99%

How does suppression of IGF-1 signaling by DNA damage affect aging and longevity?

Hinkal

Donehower

2008

Mechanisms of Ageing and Development

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Long-lived animals have evolved a robust set of defenses to maintain genomic integrity over their entire lifespan. The DNA damage response and DNA repair pathways are critical pillars of organismal defenses, minimizing somatic mutations in both post-mitotic and mitotic cells. These genomic maintenance systems not only prevent the premature emergence of cancers, but may also maintain normal tissue function and organismal longevity. Genetic defects in a number of DNA repair and DNA damage response genes often leads to a dramatic increase in cancer incidence; in other cases, premature aging or progeroid syndromes may be induced. In this review, we discuss two recent reports of two nucleotide excision repair deficient models that exhibit dramatic premature aging and shortened longevity. The DNA repair defects were also associated with a significant inhibition of the growth hormone/insulin-like growth factor 1 (GH/IGF-1) axis, an endocrine signaling pathway shown to influence aging and longevity in both vertebrates and invertebrates. Potential mechanisms of how DNA damage might affect IGF-1 signaling and aging are discussed, with a particular emphasis on the role of such signaling alterations in the adult tissue stem cell compartments.

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Section: Introductionmentioning

confidence: 99%

How does suppression of IGF-1 signaling by DNA damage affect aging and longevity?

Hinkal

Donehower

2008

Mechanisms of Ageing and Development

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“…Mutant larvae grown at 25° C constitutively enter dauer stage, whereas adults cultivated at 25° C have extended longevity (Gems et al, 1998). Insulin/ IGF-1 signaling has also been implicated in the aging of both flies and mice, which implies a conserved mechanism (Tatar et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Genes that may modulate longevity in C. elegans in both dauer larvae and long-lived daf-2 adults

Ruzanov

Riddle

Marra

et al. 2007

Experimental Gerontology

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SummaryWe used Serial Analysis of Gene Expression (SAGE) to compare the global transcription profiles of long-lived mutant daf-2 adults and dauer larvae, aiming to identify aging-related genes based on similarity of expression patterns. Genes that are expressed similarly in both long-lived types potentially define a common life-extending program. Comparison of eight SAGE libraries yielded a set of 120 genes, the expression of which was significantly different in long-lived worms versus normal adults. The gene annotations indicate a strong link between oxidative stress and life span, further supporting the hypothesis that metabolic activity is a major determinant in longevity. The SAGE data show changes in mRNA levels for electron transport chain components, elevated expression of glyoxylate shunt enzymes and significantly reduced expression for components of the TCA cycle in longer-lived nematodes. We propose a model for enhanced longevity through a cytochrome c oxidase-mediated reduction in reactive oxygen species commonly held to be a major contributor to aging.

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“…Second, comparative methods can be used to assess the general relevance of particular aging mechanisms-that is, to elucidate whether mechanisms seen in one or a few strains or species are idiosyncratic or can be generalized to others (Martin et al 1996). For example, cell signaling pathways involving insulin and insulin-like growth factor I (IGF-1) and the genes controlling them have been shown to be important correlates of aging in representative animal models of three evolutionarily distant phyla: roundworms, fruit flies, and house mice (Tatar et al 2003). The fact that these animals are from widely divergent taxa suggests these mechanisms are evolutionarily conserved and hence important in a wide range of animals, including humans.…”

Section: Comparative Methods and The Biology Of Agingmentioning

confidence: 99%

“…It is quite possible that the use of additional animal models and cell types will reveal entirely new responses to standard biogerontological experimental paradigms, such as effects of CR, and help test and revise well-supported evolutionary and proximate theories of aging. For example, comparative studies using traditional aging model taxa have revealed the importance of insulin-like signaling pathways to biological aging, responses to CR, and tradeoffs between reproduction and somatic maintenance (Weindruch and Walford 1988;Tatar et al 2003;Partridge et al 2005;Tu et al 2005;Finch 2007). New animal models can be used to test whether observations obtained using traditional models can be generalized to new taxa.…”

Section: Additional Alternative Animal Models and Experimental Approamentioning

confidence: 99%

“…At its best, the aging research community encourages communication among scientists from a variety of intellectual backgrounds, and integrates state-of-the art approaches to understanding "ultimate" (evolutionary via comparative, and population-level studies), as well as "proximate" (molecular, biochemical, cellular or physiological) mechanisms responsible for organismal senescence, aging-related dysfunction and disease. Biogerontology currently represents a dynamic synthesis of diverse intellectual perspectives on aging patterns and mechanisms; these include evolutionary theory, population biology and demography, comparative biology and bioenergetics, as well as developmental biology, molecular genetics and clinical biomedical sciences (see, for example, Finch 1990Finch , 2007Rose 1991;Kenyon et al 1993;Kirkwood and Austad 2000;Tatar et al 2003;Partridge et al 2005;Speakman 2005a; Austad and Masoro 2006).…”

Section: Introductionmentioning

confidence: 99%

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Comparative and alternative approaches and novel animal models for aging research

Holmes

Kristan

2008

AGE

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This special issue of AGE showcases powerful alternative or unconventional approaches to basic aging research, including the use of exceptionally long-lived animal model species and comparative methods from evolutionary biology. In this opening paper, we introduce several of these alternative aging research themes, including the comparative phylogenetic approach. This approach applies modern inferential methods for dissecting basic physiological and biochemical mechanisms correlated with phenotypic traits including longevity, slow aging, sustained somatic maintenance, and repair of molecular damage. Comparative methods can be used to assess the general relevance of specific aging mechanismsincluding oxidative processes-to diverse animal species, as well as to assess their potential clinical relevance to humans and other mammals. We also introduce several other novel, underexploited approaches with particular relevance to biogerontology, including the use of model animal species or strains that retain natural genetic heterogeneity, studies of effects of infectious disease and parasites on aging and responses to caloric restriction, studies of reproductive aging, and naturally occurring sex differences in aging. We emphasize the importance of drawing inferences from aging phenomena in laboratory studies that can be applied to clinically relevant aging syndromes in long-lived, outbred animals, including humans.

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The Endocrine Regulation of Aging by Insulin-like Signals

Cited by 1,201 publications

References 68 publications

How does suppression of IGF-1 signaling by DNA damage affect aging and longevity?

How does suppression of IGF-1 signaling by DNA damage affect aging and longevity?

Genes that may modulate longevity in C. elegans in both dauer larvae and long-lived daf-2 adults

Comparative and alternative approaches and novel animal models for aging research

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