Increased environmental temperature normalizes energy metabolism outputs between normal and Ames dwarf mice

Darcy, Justin; McFadden, Samuel; Fang, Yimin; Berryman, Darlene E.; List, Edward O.; Milcik, Nicholas; Bartke, Andrzej

doi:10.18632/aging.101582

Cited by 13 publications

(38 citation statements)

References 27 publications

(38 reference statements)

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“…Data from the current study failed to support our original hypothesis that chronic exposure of these diminutive mutants to increased eT will reduce or eliminate their longevity advantage, by preventing increased heat loss and the consequent increase in energy demand for thermogenesis at standard animal room temperature of 23°C. In contrast to our previous studies in adult mice (Darcy et al, ; Westbrook et al, ), juvenile mice in the current study might adapt to the eT. Thus, the differences we observed in the current study are not of the same magnitude as what was observed in these mice and Ames dwarfs exposed to 30°C for 24 hr in our previous studies (Westbrook, ), or in adult Ames dwarfs housed at this eT for 4 months (Darcy et al, ).…”

Section: Conclusion and Discussioncontrasting

confidence: 99%

“…The suggested importance of exposing juvenile versus adult mice to increased eT is consistent with the well‐documented potential of early life nutritional, hormonal, or environmental interventions to influence adult phenotypic characteristics, including rate of aging and longevity (Barker, ; Bartke & Quainoo, ; Sun et al,). The data generated in adult Ames dwarf mice concerning energy metabolism (Darcy et al, ) are likely influenced by profound suppression of thyroid function in these animals.…”

Section: Conclusion and Discussionmentioning

confidence: 99%

“…Many phenotypic characteristics shared by these mutants are believed to represent mechanisms of extended longevity. These characteristics include improved insulin sensitivity and glucose clearance (Bartke, ), altered energy metabolism manifested by increased mass and activity of BAT (Darcy et al, ; Li, Knapp, & Kopchick, ), decreased respiratory quotient (RQ) and increased oxygen consumption (VO 2 ) per unit of body mass and heat production (Westbrook, Bonkowski, Strader, & Bartke, ), which, surprisingly, are associated with reduced body temperature (Hauck, Hunter, Danilovich, Kopchick, & Bartke, ; Hunter, Croson, Bartke, Gentry, & Meliska, ).…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, the increase in VO 2 and the reduction in RQ in Ames dwarf and GHRKO mice disappeared or were severely attenuated after 24 hr of acclimation to temperature of 30°C (Westbrook, ). Exposing adult male Ames dwarf mice to 30°C for 4 months led to the normalization of both VO 2 and RQ, as well as a partial normalization (i.e., impairment) of glucose homeostasis (Darcy et al, ). From these findings, we further hypothesized that chronic exposure of these mutants to increased eT (30°C) might reduce, or eliminate, their longevity advantage.…”

Section: Introductionmentioning

confidence: 99%

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Lifespan of long‐lived growth hormone receptor knockout mice was not normalized by housing at 30°C since weaning

et al. 2020

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Growth hormone receptor knockout (GHRKO) mice are remarkably long‐lived and have improved glucose homeostasis along with altered energy metabolism which manifests through decreased respiratory quotient (RQ) and increased oxygen consumption (VO2). Short‐term exposure of these animals to increased environmental temperature (eT) at 30°C can normalize their VO2 and RQ. We hypothesized that increased heat loss in the diminutive GHRKO mice housed at 23°C and the consequent metabolic adjustments to meet the increased energy demand for thermogenesis may promote extension of longevity, and preventing these adjustments by chronic exposure to increased eT will reduce or eliminate their longevity advantage. To test these hypotheses, GHRKO mice were housed at increased eT (30°C) since weaning. Here, we report that contrasting with the effects of short‐term exposure of adult GHRKO mice to 30°C, transferring juvenile GHRKO mice to chronic housing at 30°C did not normalize the examined parameters of energy metabolism and glucose homeostasis. Moreover, despite decreased expression levels of thermogenic genes in brown adipose tissue (BAT) and elevated core body temperature, the lifespan of male GHRKO mice was not reduced, while the lifespan of female GHRKO mice was increased, along with improved glucose homeostasis. The results indicate that GHRKO mice have intrinsic features that help maintain their delayed, healthy aging, and extended longevity at both 23°C and 30°C.

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“…Accordingly, the long-lived GHRKO and Ames mice exhibit improved glucose homeostasis and energy metabolism evidenced by decreased respiratory quotient (RQ) and increased oxygen consumption (VO 2 ). In contrast, bGH mice, with high GH/IGF-1 levels show decreased VO(2) and increased RQ [30,32,33]. Taken together, these animal models suggest that diminished GH/IGF-1 activity improves mitochondrial flexibility and increases the capacity for fat oxidation.…”

Section: Gh/ Igf-1 Effects On Mitochondrial Respiration and Atp Produmentioning

confidence: 92%

Effects of GH/IGF on the Aging Mitochondria

Poudel

Dixit

Neginskaya

et al. 2020

Cells

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The mitochondria are key organelles regulating vital processes in the eukaryote cell. A decline in mitochondrial function is one of the hallmarks of aging. Growth hormone (GH) and the insulin-like growth factor-1 (IGF-1) are somatotropic hormones that regulate cellular homeostasis and play significant roles in cell differentiation, function, and survival. In mammals, these hormones peak during puberty and decline gradually during adulthood and aging. Here, we review the evidence that GH and IGF-1 regulate mitochondrial mass and function and contribute to specific processes of cellular aging. Specifically, we discuss the contribution of GH and IGF-1 to mitochondrial biogenesis, respiration and ATP production, oxidative stress, senescence, and apoptosis. Particular emphasis was placed on how these pathways intersect during aging.

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Increased environmental temperature normalizes energy metabolism outputs between normal and Ames dwarf mice

Cited by 13 publications

References 27 publications

Lifespan of long‐lived growth hormone receptor knockout mice was not normalized by housing at 30°C since weaning

Effects of GH/IGF on the Aging Mitochondria

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