PMID- 28400571
OWN - NLM
STAT- MEDLINE
DCOM- 20180918
LR  - 20181202
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 7
IP  - 1
DP  - 2017 Apr 11
TI  - Moderate lifelong overexpression of tuberous sclerosis complex 1 (TSC1) improves 
      health and survival in mice.
PG  - 834
LID - 10.1038/s41598-017-00970-7 [doi]
LID - 834
AB  - The tuberous sclerosis complex 1/2 (TSC1/2) is an endogenous regulator of the 
      mechanistic target of rapamycin (mTOR). While mTOR has been shown to play an 
      important role in health and aging, the role of TSC1/2 in aging has not been 
      fully investigated. In the current study, a constitutive TSC1 transgenic (Tsc1 
      (tg) ) mouse model was generated and characterized. mTORC1 signaling was reduced 
      in majority of the tissues, except the brain. In contrast, mTORC2 signaling was 
      enhanced in Tsc1 (tg) mice. Tsc1 (tg) mice are more tolerant to exhaustive 
      exercises and less susceptible to isoproterenol-induced cardiac hypertrophy at 
      both young and advanced ages. Tsc1 (tg) mice have less fibrosis and inflammation 
      in aged as well as isoproterenol-challenged heart than age-matched wild type 
      mice. The female Tsc1 (tg) mice exhibit a higher fat to lean mass ratio at 
      advanced ages than age-matched wild type mice. More importantly, the lifespan 
      increased significantly in female Tsc1 (tg) mice, but not in male Tsc1 (tg) mice. 
      Collectively, our data demonstrated that moderate increase of TSC1 expression can 
      enhance overall health, particularly cardiovascular health, and improve survival 
      in a gender-specific manner.
FAU - Zhang, Hong-Mei
AU  - Zhang HM
AD  - Department of Oncology, Xijing Hospital, Fourth Military Medical University, No. 
      169, Changle West Road, Xi'an, Shanxi, 710032, P. R. China. zhm@fmmu.edu.cn.
FAU - Diaz, Vivian
AU  - Diaz V
AD  - Sam and Ann Barshop Institute for Longevity and Aging Studies, University of 
      Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, 
      Texas, 78229, USA.
FAU - Walsh, Michael E
AU  - Walsh ME
AD  - Department of Cellular and Structural Biology, University of Texas Health Science 
      Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas, 78229, USA.
AD  - ETH Zurich, Department of Health Sciences and Technology LFW C 13.2, 
      Universitatstrasse 2, 8092, Zurich, Switzerland.
FAU - Zhang, Yiqiang
AU  - Zhang Y
AD  - Greehey Children's Cancer Research Institute, University of Texas Health Science 
      Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas, 78229, USA. 
      zhangy@uthscsa.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170411
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Tsc1 protein, mouse)
RN  - 0 (Tuberous Sclerosis Complex 1 Protein)
RN  - 0 (Tuberous Sclerosis Complex 2 Protein)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 2)
RN  - L628TT009W (Isoproterenol)
SB  - IM
MH  - Adiposity/genetics
MH  - Animals
MH  - Brain/metabolism
MH  - Cardiomegaly/etiology/genetics
MH  - Female
MH  - Isoproterenol/toxicity
MH  - Longevity/*genetics
MH  - Male
MH  - Mechanistic Target of Rapamycin Complex 1/metabolism
MH  - Mechanistic Target of Rapamycin Complex 2/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Physical Exertion
MH  - Sex Factors
MH  - Signal Transduction
MH  - Tuberous Sclerosis Complex 1 Protein
MH  - Tuberous Sclerosis Complex 2 Protein
MH  - Tumor Suppressor Proteins/*genetics/metabolism
MH  - Up-Regulation
PMC - PMC5429778
COIS- The authors declare that they have no competing interests.
EDAT- 2017/04/13 06:00
MHDA- 2018/09/19 06:00
PMCR- 2017/04/11
CRDT- 2017/04/13 06:00
PHST- 2016/10/14 00:00 [received]
PHST- 2017/03/10 00:00 [accepted]
PHST- 2017/04/13 06:00 [entrez]
PHST- 2017/04/13 06:00 [pubmed]
PHST- 2018/09/19 06:00 [medline]
PHST- 2017/04/11 00:00 [pmc-release]
AID - 10.1038/s41598-017-00970-7 [pii]
AID - 970 [pii]
AID - 10.1038/s41598-017-00970-7 [doi]
PST - epublish
SO  - Sci Rep. 2017 Apr 11;7(1):834. doi: 10.1038/s41598-017-00970-7.