PMID- 25540326
OWN - NLM
STAT- MEDLINE
DCOM- 20150818
LR  - 20220318
IS  - 1946-6242 (Electronic)
IS  - 1946-6234 (Linking)
VI  - 6
IP  - 268
DP  - 2014 Dec 24
TI  - mTOR inhibition improves immune function in the elderly.
PG  - 268ra179
LID - 10.1126/scitranslmed.3009892 [doi]
AB  - Inhibition of the mammalian target of rapamycin (mTOR) pathway extends life span 
      in all species studied to date, and in mice delays the onset of age-related 
      diseases and comorbidities. However, it is unknown if mTOR inhibition affects 
      aging or its consequences in humans. To begin to assess the effects of mTOR 
      inhibition on human aging-related conditions, we evaluated whether the mTOR 
      inhibitor RAD001 ameliorated immunosenescence (the decline in immune function 
      during aging) in elderly volunteers, as assessed by their response to influenza 
      vaccination. RAD001 enhanced the response to the influenza vaccine by about 20% 
      at doses that were relatively well tolerated. RAD001 also reduced the percentage 
      of CD4 and CD8 T lymphocytes expressing the programmed death-1 (PD-1) receptor, 
      which inhibits T cell signaling and is more highly expressed with age. These 
      results raise the possibility that mTOR inhibition may have beneficial effects on 
      immunosenescence in the elderly.
CI  - Copyright (c) 2014, American Association for the Advancement of Science.
FAU - Mannick, Joan B
AU  - Mannick JB
AD  - Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA. 
      joan.mannick@novartis.com.
FAU - Del Giudice, Giuseppe
AU  - Del Giudice G
AD  - Novartis Vaccines and Diagnostics, 53100 Siena, Italy.
FAU - Lattanzi, Maria
AU  - Lattanzi M
AD  - Novartis Vaccines and Diagnostics, 53100 Siena, Italy.
FAU - Valiante, Nicholas M
AU  - Valiante NM
AD  - Novartis Vaccines and Diagnostics, Cambridge, MA 02139, USA.
FAU - Praestgaard, Jens
AU  - Praestgaard J
AD  - Novartis Pharmaceuticals Corporation, East Hanover, NJ 07936, USA.
FAU - Huang, Baisong
AU  - Huang B
AD  - Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA.
FAU - Lonetto, Michael A
AU  - Lonetto MA
AD  - Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA.
FAU - Maecker, Holden T
AU  - Maecker HT
AD  - Novartis Pharmaceuticals Corporation, CH-4002 Basel, Switzerland.
FAU - Kovarik, John
AU  - Kovarik J
AD  - Stanford University School of Medicine, Stanford, CA 94305-5124, USA.
FAU - Carson, Simon
AU  - Carson S
AD  - Southern Clinical Trials, Christchurch 8024, New Zealand.
FAU - Glass, David J
AU  - Glass DJ
AD  - Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA.
FAU - Klickstein, Lloyd B
AU  - Klickstein LB
AD  - Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Sci Transl Med
JT  - Science translational medicine
JID - 101505086
RN  - 0 (Antibodies, Viral)
RN  - 0 (Influenza Vaccines)
RN  - 0 (PDCD1 protein, human)
RN  - 0 (Placebos)
RN  - 0 (Programmed Cell Death 1 Receptor)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 9HW64Q8G6G (Everolimus)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
CIN - Oncotarget. 2015 Jan 20;6(2):590-1. PMID: 25612254
MH  - Aged
MH  - Antibodies, Viral/immunology
MH  - CD4-Positive T-Lymphocytes/drug effects/immunology
MH  - CD8-Positive T-Lymphocytes/drug effects/immunology
MH  - Cohort Studies
MH  - Everolimus
MH  - Humans
MH  - Immunity/*drug effects
MH  - Influenza Vaccines/immunology
MH  - Placebos
MH  - Programmed Cell Death 1 Receptor/metabolism
MH  - Protein Kinase Inhibitors/*pharmacology
MH  - Seasons
MH  - Sirolimus/analogs & derivatives/pharmacology
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors/metabolism
MH  - Vaccination
EDAT- 2014/12/30 06:00
MHDA- 2015/08/19 06:00
CRDT- 2014/12/26 06:00
PHST- 2014/12/26 06:00 [entrez]
PHST- 2014/12/30 06:00 [pubmed]
PHST- 2015/08/19 06:00 [medline]
AID - 6/268/268ra179 [pii]
AID - 10.1126/scitranslmed.3009892 [doi]
PST - ppublish
SO  - Sci Transl Med. 2014 Dec 24;6(268):268ra179. doi: 10.1126/scitranslmed.3009892.