Enhanced longevity and metabolism by brown adipose tissue with disruption of the regulator of G protein signaling 14

Dorothy Vatner, Jie Zhang, Marko Oydanich, John Guers, Elena Katsyuba, Lin Yan, David Sinclair, Johan Auwerx, Stephen Vatner

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Disruption of the regulator for G protein signaling 14 (RGS14) knockout (KO) in mice extends their lifespan and has multiple beneficial effects related to healthful aging, that is, protection from obesity, as reflected by reduced white adipose tissue, protection against cold exposure, and improved metabolism. The observed beneficial effects were mediated by improved mitochondrial function. But most importantly, the main mechanism responsible for the salutary properties of the RGS14 KO involved an increase in brown adipose tissue (BAT), which was confirmed by surgical BAT removal and transplantation to wild-type (WT) mice, a surgical simulation of a molecular knockout. This technique reversed the phenotype of the RGS14 KO and WT, resulting in loss of the improved metabolism and protection against cold exposure in RGS14 KO and conferring this protection to the WT BAT recipients. Another mechanism mediating the salutary features in the RGS14 KO was increased SIRT3. This mechanism was confirmed in the RGS14 X SIRT3 double KO, which no longer demonstrated improved metabolism and protection against cold exposure. Loss of function of the Caenorhabditis elegans RGS-14 homolog confirmed the evolutionary conservation of this mechanism. Thus, disruption of RGS14 is a model of healthful aging, as it not only enhances lifespan, but also protects against obesity and cold exposure and improves metabolism with a key mechanism of increased BAT, which, when removed, eliminates the features of healthful aging.

Original languageEnglish (US)
Article numbere12751
JournalAging cell
Volume17
Issue number4
DOIs
StatePublished - Aug 1 2018

Fingerprint

GTP-Binding Protein Regulators
Brown Adipose Tissue
Obesity
Tissue Transplantation
White Adipose Tissue
Caenorhabditis elegans
Knockout Mice
Phenotype

All Science Journal Classification (ASJC) codes

  • Aging
  • Cell Biology

Keywords

  • G proteins
  • brown adipose tissue
  • longevity
  • obesity

Cite this

Vatner, Dorothy ; Zhang, Jie ; Oydanich, Marko ; Guers, John ; Katsyuba, Elena ; Yan, Lin ; Sinclair, David ; Auwerx, Johan ; Vatner, Stephen. / Enhanced longevity and metabolism by brown adipose tissue with disruption of the regulator of G protein signaling 14. In: Aging cell. 2018 ; Vol. 17, No. 4.
@article{a7ea76409d83429599c1c0968aae0ef8,
title = "Enhanced longevity and metabolism by brown adipose tissue with disruption of the regulator of G protein signaling 14",
abstract = "Disruption of the regulator for G protein signaling 14 (RGS14) knockout (KO) in mice extends their lifespan and has multiple beneficial effects related to healthful aging, that is, protection from obesity, as reflected by reduced white adipose tissue, protection against cold exposure, and improved metabolism. The observed beneficial effects were mediated by improved mitochondrial function. But most importantly, the main mechanism responsible for the salutary properties of the RGS14 KO involved an increase in brown adipose tissue (BAT), which was confirmed by surgical BAT removal and transplantation to wild-type (WT) mice, a surgical simulation of a molecular knockout. This technique reversed the phenotype of the RGS14 KO and WT, resulting in loss of the improved metabolism and protection against cold exposure in RGS14 KO and conferring this protection to the WT BAT recipients. Another mechanism mediating the salutary features in the RGS14 KO was increased SIRT3. This mechanism was confirmed in the RGS14 X SIRT3 double KO, which no longer demonstrated improved metabolism and protection against cold exposure. Loss of function of the Caenorhabditis elegans RGS-14 homolog confirmed the evolutionary conservation of this mechanism. Thus, disruption of RGS14 is a model of healthful aging, as it not only enhances lifespan, but also protects against obesity and cold exposure and improves metabolism with a key mechanism of increased BAT, which, when removed, eliminates the features of healthful aging.",
keywords = "G proteins, brown adipose tissue, longevity, obesity",
author = "Dorothy Vatner and Jie Zhang and Marko Oydanich and John Guers and Elena Katsyuba and Lin Yan and David Sinclair and Johan Auwerx and Stephen Vatner",
year = "2018",
month = "8",
day = "1",
doi = "10.1111/acel.12751",
language = "English (US)",
volume = "17",
journal = "Aging Cell",
issn = "1474-9718",
publisher = "Wiley-Blackwell",
number = "4",

}

Enhanced longevity and metabolism by brown adipose tissue with disruption of the regulator of G protein signaling 14. / Vatner, Dorothy; Zhang, Jie; Oydanich, Marko; Guers, John; Katsyuba, Elena; Yan, Lin; Sinclair, David; Auwerx, Johan; Vatner, Stephen.

In: Aging cell, Vol. 17, No. 4, e12751, 01.08.2018.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Enhanced longevity and metabolism by brown adipose tissue with disruption of the regulator of G protein signaling 14

AU - Vatner, Dorothy

AU - Zhang, Jie

AU - Oydanich, Marko

AU - Guers, John

AU - Katsyuba, Elena

AU - Yan, Lin

AU - Sinclair, David

AU - Auwerx, Johan

AU - Vatner, Stephen

PY - 2018/8/1

Y1 - 2018/8/1

N2 - Disruption of the regulator for G protein signaling 14 (RGS14) knockout (KO) in mice extends their lifespan and has multiple beneficial effects related to healthful aging, that is, protection from obesity, as reflected by reduced white adipose tissue, protection against cold exposure, and improved metabolism. The observed beneficial effects were mediated by improved mitochondrial function. But most importantly, the main mechanism responsible for the salutary properties of the RGS14 KO involved an increase in brown adipose tissue (BAT), which was confirmed by surgical BAT removal and transplantation to wild-type (WT) mice, a surgical simulation of a molecular knockout. This technique reversed the phenotype of the RGS14 KO and WT, resulting in loss of the improved metabolism and protection against cold exposure in RGS14 KO and conferring this protection to the WT BAT recipients. Another mechanism mediating the salutary features in the RGS14 KO was increased SIRT3. This mechanism was confirmed in the RGS14 X SIRT3 double KO, which no longer demonstrated improved metabolism and protection against cold exposure. Loss of function of the Caenorhabditis elegans RGS-14 homolog confirmed the evolutionary conservation of this mechanism. Thus, disruption of RGS14 is a model of healthful aging, as it not only enhances lifespan, but also protects against obesity and cold exposure and improves metabolism with a key mechanism of increased BAT, which, when removed, eliminates the features of healthful aging.

AB - Disruption of the regulator for G protein signaling 14 (RGS14) knockout (KO) in mice extends their lifespan and has multiple beneficial effects related to healthful aging, that is, protection from obesity, as reflected by reduced white adipose tissue, protection against cold exposure, and improved metabolism. The observed beneficial effects were mediated by improved mitochondrial function. But most importantly, the main mechanism responsible for the salutary properties of the RGS14 KO involved an increase in brown adipose tissue (BAT), which was confirmed by surgical BAT removal and transplantation to wild-type (WT) mice, a surgical simulation of a molecular knockout. This technique reversed the phenotype of the RGS14 KO and WT, resulting in loss of the improved metabolism and protection against cold exposure in RGS14 KO and conferring this protection to the WT BAT recipients. Another mechanism mediating the salutary features in the RGS14 KO was increased SIRT3. This mechanism was confirmed in the RGS14 X SIRT3 double KO, which no longer demonstrated improved metabolism and protection against cold exposure. Loss of function of the Caenorhabditis elegans RGS-14 homolog confirmed the evolutionary conservation of this mechanism. Thus, disruption of RGS14 is a model of healthful aging, as it not only enhances lifespan, but also protects against obesity and cold exposure and improves metabolism with a key mechanism of increased BAT, which, when removed, eliminates the features of healthful aging.

KW - G proteins

KW - brown adipose tissue

KW - longevity

KW - obesity

UR - http://www.scopus.com/inward/record.url?scp=85045282481&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85045282481&partnerID=8YFLogxK

U2 - 10.1111/acel.12751

DO - 10.1111/acel.12751

M3 - Article

C2 - 29654651

AN - SCOPUS:85045282481

VL - 17

JO - Aging Cell

JF - Aging Cell

SN - 1474-9718

IS - 4

M1 - e12751

ER -