PXD021447

PXD021447 is an original dataset announced via ProteomeXchange.

Title	Restoration of energy homeostasis by SIRT6 extends healthy lifespan
Description	Aging leads to a gradual decline in physical activity and disrupted energy homeostasis. The NAD+-dependent SIRT6 deacylase regulates aging and metabolism through mechanisms that largely remain unknown. Here, we show that SIRT6 overexpression leads to a reduction in frailty and lifespan extension in both male and female B6 mice. A combination of physiological assays, in vivo multi-omics analyses and 13C lactate tracing identified an age-dependent decline in glucose homeostasis and hepatic gluconeogenesis (GNG) capacity in wild type mice. In contrast, aged SIRT6-transgenic mice preserve GNG capacity and glucose homeostasis through an improvement in the utilization of two major GNG precursors, lactate and glycerol. To mediate these changes, mechanistically, SIRT6 increases hepatic GNG gene expression, de novo NAD+ synthesis, and systemically enhances glycerol release from adipose tissue. These findings show that SIRT6 optimizes energy homeostasis in old age to delay frailty and preserve healthy aging.
HostingRepository	PRIDE
AnnounceDate	2021-03-11
AnnouncementXML	Submission_2021-03-11_11:25:40.612.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ceereena Ubaida-Mohien
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	carbamoylated residue; monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-09-13 23:40:34	ID requested
⏵ 1	2021-03-11 11:25:40	announced

Dataset with its publication pending

submitter keyword: SIRT6, Aging, Gluconeogenesis, Glucose homeostasis, multi-omics

Haim Y. Cohen
contact affiliation	The Mina & Everard Goodman Faculty of Life Sciences Bar-Ilan University Ramat-Gan 52900, Israel
contact email	Haim.Cohen@biu.ac.il
lab head
Ceereena Ubaida-Mohien
contact affiliation	NIA
contact email	ceereena.ubaida-mohien@nih.gov
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/03/PXD021447

PRIDE project URI

• PRIDE
  1. PXD021447
     1. Label: PRIDE project
     2. Name: Restoration of energy homeostasis by SIRT6 extends healthy lifespan