Telomere length and telomerase activity in T cells are biomarkers of high-performing centenarians.
Adult
Aged
Aged, 80 and over
Aging
/ genetics
Biomarkers
/ metabolism
Cell Proliferation
DNA Replication
Female
Gene Expression Profiling
Gene Expression Regulation, Developmental
Genome, Human
Humans
Lymphocyte Activation
/ genetics
Male
Middle Aged
T-Lymphocytes
/ metabolism
Telomerase
/ metabolism
Telomere
/ metabolism
Telomere Homeostasis
Young Adult
centenarians
healthy aging
longevity
stimulated T cells
telomerase activity
telomeres
Journal
Aging cell
ISSN: 1474-9726
Titre abrégé: Aging Cell
Pays: England
ID NLM: 101130839
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
14
04
2018
revised:
22
08
2018
accepted:
15
09
2018
pubmed:
30
11
2018
medline:
31
3
2020
entrez:
30
11
2018
Statut:
ppublish
Résumé
It is generally recognized that the function of the immune system declines with increased age and one of the major immune changes is impaired T-cell responses upon antigen presentation/stimulation. Some "high-performing" centenarians (100+ years old) are remarkably successful in escaping, or largely postponing, major age-related diseases. However, the majority of centenarians ("low-performing") have experienced these pathologies and are forced to reside in long-term nursing facilities. Previous studies have pooled all centenarians examining heterogeneous populations of resting/unstimulated peripheral blood mononuclear cells (PBMCs). T cells represent around 60% of PBMC and are in a quiescence state when unstimulated. However, upon stimulation, T cells rapidly divide and exhibit dramatic changes in gene expression. We have compared stimulated T-cell responses and identified a set of transcripts expressed in vitro that are dramatically different in high- vs. low-performing centenarians. We have also identified several other measurements that are different between high- and low-performing centenarians: (a) The amount of proliferation following in vitro stimulation is dramatically greater in high-performing centenarians compared to 67- to 83-year-old controls and low-performing centenarians; (b) telomere length is greater in the high-performing centenarians; and (c) telomerase activity following stimulation is greater in the high-performing centenarians. In addition, we have validated a number of genes whose expression is directly related to telomere length and these are potential fundamental biomarkers of aging that may influence the risk and progression of multiple aging conditions.
Identifiants
pubmed: 30488553
doi: 10.1111/acel.12859
pmc: PMC6351827
doi:
Substances chimiques
Biomarkers
0
Telomerase
EC 2.7.7.49
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e12859Subventions
Organisme : NIH HHS
ID : AG01228
Pays : United States
Organisme : Harold Simmons National Cancer Institute Designated Comprehensive Cancer Center
ID : CA142543
Pays : International
Organisme : NIH HHS
ID : C06 RR30414
Pays : United States
Informations de copyright
© 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
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