Dwarf mice and the ageing process

Brown‐Borg, Holly M.; Borg, Kurt E.; Meliska, Charles J.; Bartke, Andrzej

doi:10.1038/384033a0

Cited by 979 publications

(674 citation statements)

References 6 publications

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“…The increase in lifespan extension is comparable to that achieved by caloric restriction (Turturro et al, 1999). While the FGF21-mediated increase in longevity is less than the 50–70% increase seen in pituitary loss-of-function Ames mice and GH receptor/GH binding protein-knockout mice (Brown-Borg et al, 1996; Coschigano et al, 2000), it is similar to that seen in other loss-of-function dwarf models including hypopituitary Snell mice (Flurkey et al, 2002) and mice lacking pregnancy-associated plasma protein-A (PAPP-A), a protease that increases IGF-1 activity (Conover et al, 2010). The FGF21-Tg mice share other phenotypic similarities with long-lived dwarf mice including small size, reduced circulating insulin and IGF-1 concentrations, increased circulating adiponectin levels and female infertility.…”

Section: Discussionmentioning

confidence: 99%

The starvation hormone, fibroblast growth factor-21, extends lifespan in mice

Zhang

Xie

Berglund

et al. 2012

eLife

332

252

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Fibroblast growth factor-21 (FGF21) is a hormone secreted by the liver during fasting that elicits diverse aspects of the adaptive starvation response. Among its effects, FGF21 induces hepatic fatty acid oxidation and ketogenesis, increases insulin sensitivity, blocks somatic growth and causes bone loss. Here we show that transgenic overexpression of FGF21 markedly extends lifespan in mice without reducing food intake or affecting markers of NAD+ metabolism or AMP kinase and mTOR signaling. Transcriptomic analysis suggests that FGF21 acts primarily by blunting the growth hormone/insulin-like growth factor-1 signaling pathway in liver. These findings raise the possibility that FGF21 can be used to extend lifespan in other species.DOI: http://dx.doi.org/10.7554/eLife.00065.001

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Section: Discussionmentioning

confidence: 99%

The starvation hormone, fibroblast growth factor-21, extends lifespan in mice

Zhang

Xie

Berglund

et al. 2012

eLife

332

252

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“…Furthermore, reduction of visceral fat by omentectomy produced significant positive and long‐term effects on glucose homeostasis in humans (Thorne et al ., 2002). Ames dwarf mice have increased subcutaneous and visceral adiposity and yet are more insulin sensitive and live much longer than control mice (Brown‐Borg et al ., 1996; Bartke, 2008) . It was recently reported that the removal of visceral adipose tissue from Ames dwarf mice decreased their insulin sensitivity compared to sham‐operated Ames dwarf mice, yet they remained more insulin sensitive than normal mice (Menon et al ., 2014).…”

Section: Discussionmentioning

confidence: 99%

“…Abnormal high levels of GH can contribute to the induction of insulin resistance (Weaver et al ., 1995), alter inflammatory cytokine levels (Uronen‐Hansson et. al ., 2003; Bartke, 2008), and can reduce life expectancy in both mice (Brown‐Borg et al ., 1996; Bartke et al ., 1998) and humans (Chertman et al ., 2000). Disruption of GH signaling by either reducing plasma GH levels or by GH receptor deletion significantly extends lifespan in mice as reported in Ames dwarf mice, Snell dwarf mice, GH receptor/GH‐binding protein gene knockout mice (GHR‐KO mice), and GH‐releasing hormone knockout mice (GHRH‐KO) (Brown‐Borg et al ., 1996; Coschigano et al ., 2000; Bartke et al ., 2011).…”

Section: Introductionmentioning

confidence: 99%

Long‐lived hypopituitary Ames dwarf mice are resistant to the detrimental effects of high‐fat diet on metabolic function and energy expenditure

Hill

Fang

Miquet³

et al. 2016

Aging Cell

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SummaryGrowth hormone (GH) signaling stimulates the production of IGF‐1; however, increased GH signaling may induce insulin resistance and can reduce life expectancy in both mice and humans. Interestingly, disruption of GH signaling by reducing plasma GH levels significantly improves health span and extends lifespan in mice, as observed in Ames dwarf mice. In addition, these mice have increased adiposity, yet are more insulin sensitive compared to control mice. Metabolic stressors such as high‐fat diet (HFD) promote obesity and may alter longevity through the GH signaling pathway. Therefore, our objective was to investigate the effects of a HFD (metabolic stressor) on genetic mechanisms that regulate metabolism during aging. We show that Ames dwarf mice fed HFD for 12 weeks had an increase in subcutaneous and visceral adiposity as a result of diet‐induced obesity, yet are more insulin sensitive and have higher levels of adiponectin compared to control mice fed HFD. Furthermore, energy expenditure was higher in Ames dwarf mice fed HFD than in control mice fed HFD. Additionally, we show that transplant of epididymal white adipose tissue (eWAT) from Ames dwarf mice fed HFD into control mice fed HFD improves their insulin sensitivity. We conclude that Ames dwarf mice are resistant to the detrimental metabolic effects of HFD and that visceral adipose tissue of Ames dwarf mice improves insulin sensitivity in control mice fed HFD.

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“…Such data, in a limited manner, have been addressed for the closely related long‐lived Ames Dwarf mutant ( Prop1 df/ df ) mice which also exhibit deficiencies in growth hormone, thyrotropin, and prolactin (Brown‐Borg, Borg, Meliska, & Bartke, 1996). For these mice, percent lean body mass values were determined to be comparable (at 2 months of age) or increased (4.5–6 months of age) relative to age‐matched controls (Heiman, Tinsley, Mattison, Hauck, & Bartke, 2003).…”

Section: Introductionmentioning

confidence: 99%

VCAM‐1 upregulation accompanies muscle remodeling following resistance‐type exercise in Snell dwarf (Pit1^dw/dw) mice

et al. 2018

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Snell dwarf mice (Pit1dw/dw) exhibit deficiencies in growth hormone, prolactin, and thyroid stimulating hormone. Besides being an experimental model of hypopituitarism, these mice are long‐lived (>40% lifespan extension) and utilized as a model of slowed/delayed aging. Whether this longevity is accompanied by a compromised quality of life in terms of muscular performance has not yet been characterized. In this study, we investigated nontrained and trained muscles 1 month following a general validated resistance‐type exercise protocol in 3‐month‐old Snell dwarf mice and control littermates. Nontrained Snell dwarf gastrocnemius muscles exhibited a 1.3‐fold greater muscle mass to body weight ratio than control values although muscle quality, maximum isometric torque normalized to muscle mass, and fatigue recovery were compromised. For control mice, training increased isometric torque (17%) without altering muscle mass. For Snell dwarf mice, isometric torque was unaltered by training despite decreased muscle mass that rendered muscle mass to body weight ratio comparable to control values. Muscle quality and fatigue recovery improved twofold and threefold, respectively, for Snell dwarf mice. This accompanied a fourfold increase in levels of vascular cell adhesion molecule‐1 (VCAM‐1), a mediator of progenitor cell recruitment, and muscle remodeling in the form of increased number of central nuclei, additional muscle fibers per unit area, and altered fiber type distribution. These results reveal a trade‐off between muscle quality and longevity in the context of anterior pituitary hormone deficiency and that resistance‐type training can diminish this trade‐off by improving muscle quality concomitant with VCAM‐1 upregulation and muscle remodeling.

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Dwarf mice and the ageing process

Cited by 979 publications

References 6 publications

The starvation hormone, fibroblast growth factor-21, extends lifespan in mice

The starvation hormone, fibroblast growth factor-21, extends lifespan in mice

Long‐lived hypopituitary Ames dwarf mice are resistant to the detrimental effects of high‐fat diet on metabolic function and energy expenditure

VCAM‐1 upregulation accompanies muscle remodeling following resistance‐type exercise in Snell dwarf (Pit1^dw/dw) mice

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Dwarf mice and the ageing process

Cited by 979 publications

References 6 publications

The starvation hormone, fibroblast growth factor-21, extends lifespan in mice

The starvation hormone, fibroblast growth factor-21, extends lifespan in mice

Long‐lived hypopituitary Ames dwarf mice are resistant to the detrimental effects of high‐fat diet on metabolic function and energy expenditure

VCAM‐1 upregulation accompanies muscle remodeling following resistance‐type exercise in Snell dwarf (Pit1dw/dw) mice

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VCAM‐1 upregulation accompanies muscle remodeling following resistance‐type exercise in Snell dwarf (Pit1^dw/dw) mice