PMID- 25934099
OWN - NLM
STAT- MEDLINE
DCOM- 20150915
LR  - 20211203
IS  - 1522-1539 (Electronic)
IS  - 0363-6135 (Linking)
VI  - 309
IP  - 1
DP  - 2015 Jul 1
TI  - Angiotensin II blockade: how its molecular targets may signal to mitochondria and 
      slow aging. Coincidences with calorie restriction and mTOR inhibition.
PG  - H15-44
LID - 10.1152/ajpheart.00459.2014 [doi]
AB  - Caloric restriction (CR), renin angiotensin system blockade (RAS-bl), and 
      rapamycin-mediated mechanistic target of rapamycin (mTOR) inhibition increase 
      survival and retard aging across species. Previously, we have summarized CR and 
      RAS-bl's converging effects, and the mitochondrial function changes associated 
      with their physiological benefits. mTOR inhibition and enhanced sirtuin and 
      KLOTHO signaling contribute to the benefits of CR in aging. mTORC1/mTORC2 
      complexes contribute to cell growth and metabolic regulation. Prolonged mTORC1 
      activation may lead to age-related disease progression; thus, rapamycin-mediated 
      mTOR inhibition and CR may extend lifespan and retard aging through mTORC1 
      interference. Sirtuins by deacetylating histone and transcription-related 
      proteins modulate signaling and survival pathways and mitochondrial functioning. 
      CR regulates several mammalian sirtuins favoring their role in aging regulation. 
      KLOTHO/fibroblast growth factor 23 (FGF23) contribute to control Ca(2+), 
      phosphate, and vitamin D metabolism, and their dysregulation may participate in 
      age-related disease. Here we review how mTOR inhibition extends lifespan, how 
      KLOTHO functions as an aging suppressor, how sirtuins mediate longevity, how 
      vitamin D loss may contribute to age-related disease, and how they relate to 
      mitochondrial function. Also, we discuss how RAS-bl downregulates mTOR and 
      upregulates KLOTHO, sirtuin, and vitamin D receptor expression, suggesting that 
      at least some of RAS-bl benefits in aging are mediated through the modulation of 
      mTOR, KLOTHO, and sirtuin expression and vitamin D signaling, paralleling CR 
      actions in age retardation. Concluding, the available evidence endorses the idea 
      that RAS-bl is among the interventions that may turn out to provide relief to the 
      spreading issue of age-associated chronic disease.
CI  - Copyright (c) 2015 the American Physiological Society.
FAU - de Cavanagh, Elena M V
AU  - de Cavanagh EM
AD  - Center of Hypertension, Cardiology Department, Austral University Hospital, 
      Derqui, Argentina; School of Biomedical Sciences, Austral University, Buenos 
      Aires, Argentina; and elenacavanagh@yahoo.com.ar.
FAU - Inserra, Felipe
AU  - Inserra F
AD  - Center of Hypertension, Cardiology Department, Austral University Hospital, 
      Derqui, Argentina; School of Biomedical Sciences, Austral University, Buenos 
      Aires, Argentina; and.
FAU - Ferder, Leon
AU  - Ferder L
AD  - Department of Physiology and Pharmacology, Ponce School of Medicine, Ponce, 
      Puerto Rico.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20150501
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (FGF23 protein, human)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (Receptors, Calcitriol)
RN  - 11128-99-7 (Angiotensin II)
RN  - 1406-16-2 (Vitamin D)
RN  - 62031-54-3 (Fibroblast Growth Factors)
RN  - 7Q7P4S7RRE (Fibroblast Growth Factor-23)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.2.1.31 (Glucuronidase)
RN  - EC 3.2.1.31 (Klotho Proteins)
RN  - EC 3.5.1.- (Sirtuins)
SB  - IM
MH  - Aging/*metabolism
MH  - Angiotensin II/*metabolism
MH  - *Caloric Restriction
MH  - Fibroblast Growth Factor-23
MH  - Fibroblast Growth Factors/metabolism
MH  - Glucuronidase/metabolism
MH  - Humans
MH  - Klotho Proteins
MH  - *Longevity
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - Mitochondria/*metabolism
MH  - Multiprotein Complexes/metabolism
MH  - Receptors, Calcitriol/metabolism
MH  - *Renin-Angiotensin System
MH  - Signal Transduction
MH  - Sirtuins/metabolism
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors/metabolism
MH  - Vitamin D/metabolism
OTO - NOTNLM
OT  - caloric restriction
OT  - mechanistic target of rapamycin
OT  - renin-angiotensin system
OT  - vitamin D
EDAT- 2015/05/03 06:00
MHDA- 2015/09/16 06:00
CRDT- 2015/05/03 06:00
PHST- 2014/06/30 00:00 [received]
PHST- 2015/04/30 00:00 [accepted]
PHST- 2015/05/03 06:00 [entrez]
PHST- 2015/05/03 06:00 [pubmed]
PHST- 2015/09/16 06:00 [medline]
AID - ajpheart.00459.2014 [pii]
AID - 10.1152/ajpheart.00459.2014 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2015 Jul 1;309(1):H15-44. doi: 
      10.1152/ajpheart.00459.2014. Epub 2015 May 1.