Connecting serum IGF-1, body size, and age in the domestic dog

Greer, Kimberly A.; Hughes, Larry M.; Masternak, Michał M.

doi:10.1007/s11357-010-9182-4

Cited by 72 publications

(56 citation statements)

References 41 publications

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“…There is very strong evidence that adult body size, a GH- and IGF-1-dependent trait, is negatively related to longevity in domestic dogs, a species in which selective breeding produced an astounding (greater than 100 fold) range of difference in body size [114, 115]. A similar relationship of body size and longevity was also reported in laboratory rats [33], domestic cats [116] and horses [117].…”

Section: What Is the Relevance Of Findings In Mutant Mice To Our Undementioning

confidence: 76%

GH and ageing: Pitfalls and new insights

Bartke

Darcy

2017

Best Practice & Research Clinical Endocrinology & Metab

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Interrelationships of growth hormone (GH) actions and aging are complex and incompletely understood. The very pronounced age-related decline in GH secretion together with benefits of GH therapy in individuals with congenital or adult GH deficiency (GHD) prompted interest in GH as an anti-aging agent. However, the benefits of treatment of normal elderly subjects with GH appear to be marginal and counterbalanced by worrisome side effects. In laboratory mice, genetic GH deficiency or resistance leads to a remarkable extension of longevity accompanied by signs of delayed and/or slower aging. Mechanisms believed to contribute to extended longevity of GH-related mutants include improved anti-oxidant defenses, enhanced insulin sensitivity and reduced insulin levels, reduced inflammation and cell senescence, major shifts in mitochondrial function and energy metabolism and greater stress resistance. Negative association of the somatotropic signaling and GH/insulin-like growth factor 1 (IGF-1)-dependent traits with longevity was also shown in other mammalian species. In humans, syndromes of GH resistance or deficiency have no consistent effect on longevity, but can provide striking protection from cancer, diabetes and atherosclerosis. More subtle variations in various steps of GH and IGF-1 signaling are associated with reduced old-age mortality, particularly in women and with improved chances of attaining extremes of lifespan. Epidemiological studies raise a possibility that the relationship of IGF-1 and perhaps also GH levels with human healthy aging and longevity may be biphasic. However, the impact of somatotropic signaling on neoplastic disease is difficult to separate from its impact on aging and IGF-1 levels exhibit opposite associations with different chronic, age-related diseases.

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Section: What Is the Relevance Of Findings In Mutant Mice To Our Undementioning

confidence: 76%

GH and ageing: Pitfalls and new insights

Bartke

Darcy

2017

Best Practice & Research Clinical Endocrinology & Metab

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“…Using clinical canine patients, we observed a significant difference in the incidence of vomiting in dogs that were fasted when compared to fed dogs. However, in the measurement of serum IGF-1 using an ELISA as has previously been reported in dogs [24], [25], we found no significant difference in serum IGF-1 concentration in dogs with paired data from both “fed” and “fasted” treatments, which is in agreement with two previous canine studies that have reported that fasting for 18 to 20 hours does not alter serum IGF-1 or IGFBP concentrations [26], [27]. The lack of a significant decrease in IGF-1 levels in our dogs after an 18-hour fast suggests that extending the duration of fasting might be necessary to significantly reduce the IGF-1 concentration before chemotherapy and consequently to see a maximum clinical benefit.…”

Section: Discussionmentioning

confidence: 96%

Fasting Reduces the Incidence of Delayed-Type Vomiting Associated with Doxorubicin Treatment in Dogs with Lymphoma

Withers

Kass

Rodríguez

et al. 2014

Translational Oncology

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Fasting reduces gastrointestinal cellular proliferation rates through G1 cycle blockade and can promote cellular protection of normal but not cancer cells through altered cell signaling including down-regulation of insulin-like growth factor 1 (IGF-1). Consequently, the purpose of this study was to determine the effects of fasting on delayed-type chemotherapy-induced nausea and vomiting in dogs receiving doxorubicin. This prospective randomized crossover study involved intended administration of two doses of doxorubicin. Cancer-bearing dogs were randomized to be fasted for 24 hours beginning at 6 P.M. the night before the first or second doxorubicin administration, and all treatments were administered within an hour before or after 12 P.M. Dogs were fed normally before the alternate dose. Circulating IGF-1 concentrations were determined from serum samples obtained immediately before each doxorubicin treatment. Data from 35 doses were available from 20 dogs enrolled. Dogs that were fasted exhibited a significantly lower incidence of vomiting, when compared to fed dogs (10% compared to 67%, P = .020). Furthermore, among the 15 dogs that completed crossover dosing, vomiting was abrogated in four of five dogs that experienced doxorubicin-induced vomiting when fed normally (P = .050). No differences in other gastrointestinal, constitutional, or bone marrow toxicities or serum IGF-1 levels were observed.

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“…Several studies have linked the longer lifespans and smaller body size in long-lived dog breeds to reduced circulating IGF-1 levels [76–78]. Strikingly, a genomic study attributed the small size to a single IGF-1 single-nucleotide polymorphism (SNP) present in all small breeds of dogs [79].…”

Section: Insulin/igf-1 Signalingmentioning

confidence: 99%

Molecular Mechanisms Determining Lifespan in Short- and Long-Lived Species

Tian

Seluanov

Gorbunova

2017

Trends in Endocrinology & Metabolism

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Aging is a global decline of physiological functions, leading to an increased susceptibility to diseases and ultimately death. Maximum lifespans differ up to 200-fold between mammalian species. Although considerable progress has been achieved in identifying conserved pathways that regulate individual lifespan within model organisms, whether the same pathways are responsible for the interspecies differences in longevity remains to be determined. Recent cross-species studies have begun to identify pathways responsible for interspecies differences in lifespan. Here, we review the evidence supporting the role of anti-cancer mechanisms, DNA repair machinery, insulin/IGF1 signaling, and proteostasis in defining species lifespans. Understanding the mechanisms responsible for the dramatic differences in lifespan between species will have a transformative effect on developing interventions to improve human health and longevity.

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Connecting serum IGF-1, body size, and age in the domestic dog

Cited by 72 publications

References 41 publications

GH and ageing: Pitfalls and new insights

GH and ageing: Pitfalls and new insights

Fasting Reduces the Incidence of Delayed-Type Vomiting Associated with Doxorubicin Treatment in Dogs with Lymphoma

Molecular Mechanisms Determining Lifespan in Short- and Long-Lived Species

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