Hormonal regulation of longevity in mammals

Brown‐Borg, Holly M.

doi:10.1016/j.arr.2007.02.005

Cited by 78 publications

(57 citation statements)

References 207 publications

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“…BMAL1 contributes to CR-mediated regulation of circulating IGF-1 levels. IGF-1 is important for CR-induced increase in longevity (35,36). Another pathway considered to be critical for CR mechanisms is the mTOR complex 1 (mTORC1) signaling pathway (45).…”

Section: Discussionmentioning

confidence: 99%

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Circadian clocks govern calorie restriction—mediated life span extension through BMAL1‐ and IGF‐1‐dependent mechanisms

et al. 2015

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Calorie restriction (CR) increases longevity in many species by unknown mechanisms. The circadian clock was proposed as a potential mediator of CR. Deficiency of the core component of the circadian clock--transcriptional factor BMAL1 (brain and muscle ARNT [aryl hydrocarbon receptor nuclear translocator]-like protein 1)-results in accelerated aging. Here we investigated the role of BMAL1 in mechanisms of CR. The 30% CR diet increased the life span of wild-type (WT) mice by 20% compared to mice on an ad libitum (AL) diet but failed to increase life span of Bmal1 2/2 mice. BMAL1 deficiency impaired CR-mediated changes in the plasma levels of IGF-1 and insulin. We detected a statistically significantly reduction of IGF-1 in CR vs. AL by 50 to 70% in WT mice at several daily time points tested, while in Bmal1 2/2 the reduction was not significant. Insulin levels in WT were reduced by 5 to 9%, while Bmal1 2/2 induced it by 10 to 35% at all time points tested. CR up-regulated the daily average expression of Bmal1 (by 150%) and its downstream target genes Periods (by 470% for Per1 and by 130% for Per2). We propose that BMAL1 is an important mediator of CR, and activation of BMAL1 might link CR mechanisms with biologic clocks.-Patel, S. A., Chaudhari, A., Gupta, R., Velingkaar, N., Kondratov, R. V. Circadian clocks govern calorie restriction-mediated life span extension through BMAL1-and IGF-1-dependent mechanisms. FASEB J. 30, 1634-1642 (2016). www.fasebj.orgCalorie restriction (CR) is a robust intervention that increases longevity across different species, including mammals (1-4). The precise molecular mechanisms of CR are unknown, and multiple theories have been put forward to explain CR-mediated effects on life span and health. Several physiologic systems-such as the mammalian target of rapamycin (mTOR) signaling pathway, the insulin/IGF-1 signaling pathways, and the sirtuin-controlled pathway-are affected by CR in animals and are considered to be potential mediators of CR (5-7). Activation of the NADdependent protein deacetylase sirtuin (silent mating type information regulation 2 homolog) 1 (SIRT1) is necessary for the full benefits of CR (8-11). Indeed, several behavioral and physiologic changes induced by CR in wild-type (WT) mice are impaired in SIRT1-null mice: these animals do not demonstrate an increase in daily activity (12). CR has different effects on several metabolic parameters in WT and SIRT1-null mice (13,14). Finally, there is no increase in the life span of SIRT1-null mice on CR (14).SIRT1 regulates the activity of many transcription factors. The helix-loop-helix transcription factor BMAL1 (brain and muscle ARNT [aryl hydrocarbon receptor nuclear translocator]-like protein 1) is one of the direct targets of SIRT1 (15). BMAL1 is a component of the circadian clock mechanism (16). The circadian clock is an internal timekeeping system that generates daily rhythms in physiology, metabolism, and behavior (17)(18)(19)(20). BMAL1 also has other physiologic functions, such as control of metabolism, g...

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Section: Discussionmentioning

confidence: 99%

“…BMAL1 regulates CR-mediated effects on insulin and IGF-1 levels CR significantly affects glucose, insulin, and IGF-1 levels in WT mice (35,36); therefore, we next studied these parameters in Bmal1 2/2 mice maintained on AL and CR regimens. Results of statistical analysis are presented in Supplemental Table 2.…”

Section: /2mentioning

confidence: 99%

Circadian clocks govern calorie restriction—mediated life span extension through BMAL1‐ and IGF‐1‐dependent mechanisms

et al. 2015

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“…Potential mechanisms of life span extension in mammals involve multiple systems including metabolism, growth, reproduction, stress resistance, and repair (Brown-Borg 2007). The reduction in plasma IGF-1 levels found in GHRKO mice results in reduced circulating insulin, glucose, and thyroid hormone, as well as altered reproductive capacity, hyperprolactinemia, and .05 compared to GHRKO saline.…”

Section: Discussionmentioning

confidence: 99%

Effects of insulin-like growth factor 1 on glutathione S-transferases and thioredoxin in growth hormone receptor knockout mice

Rojanathammanee

Rakoczy

Kopchick

et al. 2014

AGE

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Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) have been shown to affect processes involved in cellular stress defense, aging, and longevity. This study was designed to identify possible mechanisms of a disrupted GH signaling pathway on stress resistance using growth hormone receptor knockout (GHRKO) mice. GHRKO mice are GH resistant due to the targeted disruption of the GH receptor/ binding protein gene, thus preventing GH from binding and exerting its downstream effects. These mice have very low circulating IGF-1 levels and high GH levels, are obese yet insulin sensitive, and live longer than their wild-type controls. Wild-type or GHRKO mice were treated with saline or IGF-1 (WT saline, GHRKO saline, GHRKO IGF-1) two times daily for 7 days. Glutathione S-transferase (GST) activities, proteins, and gene expression were determined. Liver mitochondrial GSTA1, GSTA3, and GSTZ1 proteins were significantly higher in GHRKO when compared to those of WT mice. The 4-hydroxynonenal (4-HNE) GST activity was upregulated in GHRKO mice and was suppressed after IGF-1 administration. Interestingly, thioredoxin (Trx)1, Trx2, thioredoxin reductase (TrxR)1, and TrxR2 messenger RNA (mRNA) levels were significantly higher in the GHRKO as compared to WT mice, and IGF-1 treatment suppressed the expression of each. We also found that glutaredoxin (Grx)2 mRNA and cytosolic Grx activity were higher in GHRKO mice. These results suggest that the detoxification and stress response mechanisms in GHRKO mice are contributed in part by the circulating level of IGF-1.

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“…Thyroid hormone is also implicated in the regulation of longevity in animals [74,75]. Longlived species of squirrels, deer mice, bats and mole-rats maintain low levels of thyroid hormone [76,77,78,79].…”

Section: Inter-population and Geographical Variation In Thyroid Hormomentioning

confidence: 99%

Ecological Genetics of Thyroid Hormone Physiology in Humans and Wild Animals

Ishikawa¹,

Kitano²

2012

Thyroid Hormone

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Hormonal regulation of longevity in mammals

Cited by 78 publications

References 207 publications

Circadian clocks govern calorie restriction—mediated life span extension through BMAL1‐ and IGF‐1‐dependent mechanisms

Circadian clocks govern calorie restriction—mediated life span extension through BMAL1‐ and IGF‐1‐dependent mechanisms

Effects of insulin-like growth factor 1 on glutathione S-transferases and thioredoxin in growth hormone receptor knockout mice

Ecological Genetics of Thyroid Hormone Physiology in Humans and Wild Animals

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