PMID- 34256116
OWN - NLM
STAT- MEDLINE
DCOM- 20210816
LR  - 20210816
IS  - 1873-6815 (Electronic)
IS  - 0531-5565 (Linking)
VI  - 152
DP  - 2021 Sep
TI  - Gonadotropin-releasing hormone receptor pathway affects the function of human 
      EBV-transformed B lymphocytes in an age-independent way.
PG  - 111471
LID - S0531-5565(21)00253-9 [pii]
LID - 10.1016/j.exger.2021.111471 [doi]
AB  - Immune system function changes during aging, but the molecular mechanisms of this 
      phenomenon are not fully understood. The present study identified pathways that 
      are associated with age-associated changes in human B lymphocytes. Initial in 
      silico analysis of 1355 genes involved in aging revealed the strongest 
      association (p = 4.36E-21) with the gonadotropin-releasing hormone receptor 
      (GnRHR) pathway. Extended analysis of 2736 aging-related genes using updated 
      databases confirmed such association (p = 2.41E-16). Genes involved in both aging 
      and the GnRHR pathway were significantly involved in lymphocyte B and T 
      activation and aging-related phenotypes, including hyperinsulinemia and diabetes, 
      arthritis, cerebrovascular disease, and cancers. We, therefore, examined 
      non-tumorigenic Epstein-Barr virus (EBV)-transformed B-lymphocyte cell lines that 
      originated from 12 young subjects (20-31 years old) and 10 centenarians 
      (100-102 years old). Gonadotropin-releasing hormone I (GnRH-I) and GnRHR levels 
      did not depend on the age of the cell donors. Inhibition of the GnRHR pathway 
      age-independently decreased cell proliferation (p < 0.001) and increased 
      apoptosis (p < 0.001). However, the decrease in immunoglobulin G synthesis 
      (p < 0.01) was twice as high in centenarian cells than in young cells. In 
      conclusion, the GnRHR pathway regulated essential properties of B lymphocytes. 
      However, upon EBV transformation, memory class-switched B cells became the 
      dominant cell subpopulation. Therefore, the observed effects of GnRHR inhibition 
      were attributable to this subpopulation.
CI  - Copyright (c) 2021 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Walkiewicz, Dorota
AU  - Walkiewicz D
AD  - Department of Human Epigenetics, Mossakowski Medical Research Institute, PAS, 
      02-106 Warsaw, Poland; Department of Geriatrics and Gerontology, Medical Centre 
      of Postgraduate Education, 01-813 Warsaw, Poland.
FAU - Wicik, Zofia
AU  - Wicik Z
AD  - Department of Human Epigenetics, Mossakowski Medical Research Institute, PAS, 
      02-106 Warsaw, Poland. Electronic address: zofiawicik@gmail.com.
FAU - Puzianowska-Kuznicka, Monika
AU  - Puzianowska-Kuznicka M
AD  - Department of Human Epigenetics, Mossakowski Medical Research Institute, PAS, 
      02-106 Warsaw, Poland; Department of Geriatrics and Gerontology, Medical Centre 
      of Postgraduate Education, 01-813 Warsaw, Poland. Electronic address: 
      mpuzianowska@imdik.pan.pl.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210710
PL  - England
TA  - Exp Gerontol
JT  - Experimental gerontology
JID - 0047061
RN  - 0 (Receptors, LHRH)
RN  - 33515-09-2 (Gonadotropin-Releasing Hormone)
SB  - IM
MH  - Aged, 80 and over
MH  - B-Lymphocytes
MH  - *Epstein-Barr Virus Infections
MH  - Gonadotropin-Releasing Hormone
MH  - *Herpesvirus 4, Human
MH  - Humans
MH  - Receptors, LHRH/genetics
OTO - NOTNLM
OT  - Aging
OT  - B lymphocytes
OT  - GnRHR antagonist
OT  - Gonadotropin-releasing hormone (GnRH-I)
OT  - Gonadotropin-releasing hormone receptor (GnRHR)
OT  - Immune system
EDAT- 2021/07/14 06:00
MHDA- 2021/08/17 06:00
CRDT- 2021/07/13 20:11
PHST- 2021/03/12 00:00 [received]
PHST- 2021/07/02 00:00 [revised]
PHST- 2021/07/06 00:00 [accepted]
PHST- 2021/07/14 06:00 [pubmed]
PHST- 2021/08/17 06:00 [medline]
PHST- 2021/07/13 20:11 [entrez]
AID - S0531-5565(21)00253-9 [pii]
AID - 10.1016/j.exger.2021.111471 [doi]
PST - ppublish
SO  - Exp Gerontol. 2021 Sep;152:111471. doi: 10.1016/j.exger.2021.111471. Epub 2021 
      Jul 10.