TY - JOUR

T1 - Differentially Expressed Genes and Molecular Susceptibility to Human Age-Related Diseases

AU - Shikhevich, Svetlana

AU - Chadaeva, Irina

AU - Khandaev, Bato

AU - Kozhemyakina, Rimma

AU - Zolotareva, Karina

AU - Kazachek, Anna

AU - Oshchepkov, Dmitry

AU - Bogomolov, Anton

AU - Klimova, Natalya V

AU - Ivanisenko, Vladimir A

AU - Demenkov, Pavel

AU - Mustafin, Zakhar

AU - Markel, Arcady

AU - Savinkova, Ludmila

AU - Kolchanov, Nikolay A

AU - Kozlov, Vladimir

AU - Ponomarenko, Mikhail

N1 - Funding: This study was supported by the Russian Federal Science and Technology Program for the Development of Genetic Technologies.

PY - 2023/2/16

Y1 - 2023/2/16

N2 - Mainstream transcriptome profiling of susceptibility versus resistance to age-related diseases (ARDs) is focused on differentially expressed genes (DEGs) specific to gender, age, and pathogeneses. This approach fits in well with predictive, preventive, personalized, participatory medicine and helps understand how, why, when, and what ARDs one can develop depending on their genetic background. Within this mainstream paradigm, we wanted to find out whether the known ARD-linked DEGs available in PubMed can reveal a molecular marker that will serve the purpose in anyone's any tissue at any time. We sequenced the periaqueductal gray (PAG) transcriptome of tame versus aggressive rats, identified rat-behavior-related DEGs, and compared them with their known homologous animal ARD-linked DEGs. This analysis yielded statistically significant correlations between behavior-related and ARD-susceptibility-related fold changes (log2 values) in the expression of these DEG homologs. We found principal components, PC1 and PC2, corresponding to the half-sum and the half-difference of these log2 values, respectively. With the DEGs linked to ARD susceptibility and ARD resistance in humans used as controls, we verified these principal components. This yielded only one statistically significant common molecular marker for ARDs: an excess of Fcγ receptor IIb suppressing immune cell hyperactivation.

AB - Mainstream transcriptome profiling of susceptibility versus resistance to age-related diseases (ARDs) is focused on differentially expressed genes (DEGs) specific to gender, age, and pathogeneses. This approach fits in well with predictive, preventive, personalized, participatory medicine and helps understand how, why, when, and what ARDs one can develop depending on their genetic background. Within this mainstream paradigm, we wanted to find out whether the known ARD-linked DEGs available in PubMed can reveal a molecular marker that will serve the purpose in anyone's any tissue at any time. We sequenced the periaqueductal gray (PAG) transcriptome of tame versus aggressive rats, identified rat-behavior-related DEGs, and compared them with their known homologous animal ARD-linked DEGs. This analysis yielded statistically significant correlations between behavior-related and ARD-susceptibility-related fold changes (log2 values) in the expression of these DEG homologs. We found principal components, PC1 and PC2, corresponding to the half-sum and the half-difference of these log2 values, respectively. With the DEGs linked to ARD susceptibility and ARD resistance in humans used as controls, we verified these principal components. This yielded only one statistically significant common molecular marker for ARDs: an excess of Fcγ receptor IIb suppressing immune cell hyperactivation.

KW - RNA-Seq

KW - Rattus norvegicus

KW - age-related disease

KW - bootstrap

KW - correlation

KW - differentially expressed gene

KW - human

KW - meta-analysis

KW - molecular marker

KW - principal component

KW - qPCR

UR - https://www.mendeley.com/catalogue/49f96f17-6de8-3390-8844-4b76e40fc91f/

U2 - 10.3390/ijms24043996

DO - 10.3390/ijms24043996

M3 - Article

C2 - 36835409

VL - 24

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 4

M1 - 3996

ER -