Cancer History Avoids the Increase of Senescence Markers in Peripheral Cells of Amnestic Mild Cognitive Impaired Patients
Journal
International Journal of Molecular Sciences
ISSN
1422-0067
Date Issued
2023
Author(s)
Carol D. SanMartín
Felipe Salech
Daniela Paz Ponce
Jorge Concha-Cerda
Esteban Romero-Hernández
Gianella Liabeuf
Nicole K. Rogers
Paola Murgas
Bárbara Bruna
Jamileth More
Type
Resource Types::text::journal::journal article
URL Institutional Repository
Abstract
<jats:p>Epidemiological studies show that having a history of cancer protects from the development of Alzheimer’s Disease (AD), and vice versa, AD protects from cancer. The mechanism of this mutual protection is unknown. We have reported that the peripheral blood mononuclear cells (PBMC) of amnestic cognitive impairment (aMCI) and Alzheimer’s Disease (AD) patients have increased susceptibility to oxidative cell death compared to control subjects, and from the opposite standpoint a cancer history is associated with increased resistance to oxidative stress cell death in PBMCs, even in those subjects who have cancer history and aMCI (Ca + aMCI). Cellular senescence is a regulator of susceptibility to cell death and has been related to the pathophysiology of AD and cancer. Recently, we showed that cellular senescence markers can be tracked in PBMCs of aMCI patients, so we here investigated whether these senescence markers are dependent on having a history of cancer. Senescence-associated βeta-galactosidase (SA-β-Gal) activity, G0-G1 phase cell-cycle arrest, p16 and p53 were analyzed by flow cytometry; phosphorylated H2A histone family member X (γH2AX) by immunofluorescence; IL-6 and IL-8 mRNA by qPCR; and plasmatic levels by ELISA. Senescence markers that were elevated in PBMCs of aMCI patients, such as SA-β-Gal, Go-G1 arrested cells, IL-6 and IL-8 mRNA expression, and IL-8 plasmatic levels, were decreased in PBMCs of Ca + aMCI patients to levels similar to those of controls or of cancer survivors without cognitive impairment, suggesting that cancer in the past leaves a fingerprint that can be peripherally traceable in PBMC samples. These results support the hypothesis that the senescence process might be involved in the inverse association between cancer and AD.</jats:p>
Subjects
aging
;
alzheimer’s disease (ad)
;
amnestic mild cognitive impairment (amci)
;
cancer history
;
cellular senescence
;
peripheral blood mononuclear cells (pbmcs)
;
alzheimer disease
;
cognition
;
cognitive dysfunction
;
humans
;
interleukin-6
;
interleukin-8
;
leukocytes, mononuclear
;
neoplasms
;
neuropsychological tests
;
rna, messenger
;
beta galactosidase
;
cell marker
;
cholinesterase inhibitor
;
histone h2ax
;
interleukin 6
;
interleukin 8
;
memantine
;
messenger rna
;
protein p16
;
protein p53
;
interleukin 6
;
interleukin 8
;
messenger rna
;
aged
;
alzheimer disease
;
article
;
cancer survivor
;
cell aging
;
clinical article
;
controlled study
;
dna damage response
;
enzyme activity
;
enzyme linked immunosorbent assay
;
female
;
flow cytometry
;
g1 phase cell cycle checkpoint
;
histone phosphorylation
;
human
;
human cell
;
immunofluorescence
;
male
;
medical history
;
mild cognitive impairment
;
mrna expression level
;
neuroapoptosis
;
neuropathology
;
oxidative stress
;
peripheral blood mononuclear cell
;
real time polymerase chain reaction
;
senescence-associated secretory phenotype
;
very elderly
;
alzheimer disease
;
cognition
;
cognitive defect
;
genetics
;
mononuclear cell
;
neoplasm
;
neuropsychological assessment