Age-related changes to the expression of nuclear factor erythroid 2-like 2 (Nrf2), a regulatory antioxidant and xenobiotic defence gene

Greg Scutt, Andrew Overall, Prijay Bakrania, Eliseveta Krasteva, Nikesh Parekh, Khalid Ali, Graham Davies, Chakravarthi Rajkumar

Research output: Chapter in Book/Conference proceeding with ISSN or ISBNConference contribution with ISSN or ISBNResearchpeer-review

Abstract

Introduction Multimorbidity, polypharmacy and susceptibility to adverse drug reactions (ADR) are common problems in old age. Understanding the age-related biological changes that occur at a cellular level, may assist in identifying novel therapeutic targets. The nuclear factor erythroid 2-like 2 (Nrf2) transcription factor regulates antioxidant and drug metabolising pathways in the cell. Data from rodent models showed that Nrf2 protein expression declines with age. If similar findings are observed in humans, it may help to explain why older people are vulnerable to multimorbidity and ADRs. This study investigates whether Nrf2 expression (both mRNA and protein) decreases with increasing age in humans. Methods Fifty-five adults were recruited to our study (age range: 18-75 years). Participants donated 6 mL of venous blood, from which peripheral blood mononuclear cells (PBMCs) were separated and analysed for Nrf2 mRNA and protein expression (real time quantitative polymerase chain reaction and enzyme-linked immunosorbant assay respectively). Results Our data showed that Nrf2 protein expression was approximately 50% lower in individuals aged >30 years (0.065 ±0.014 EU <30 years vs. 0.033 ±0.0060 EU >30 years, p<0.05). Similarly, mRNA expression declined with advancing age (log2-fold change compared to 18-29 year-olds: 1.08±1.19, 2.14±1.25, -0.69±1.15, 0.45±2.03, -4.76±2.06, in 30-39, 40-49, 50-59, 60-69, >70 year age categories respectively; p<0.0001). Conclusions The expression of Nrf2 transcription factor is reduced in old age, potentially contributing to the increased risk of multimorbidity and adverse drug reactions.
Original languageEnglish
Title of host publication14th International Congress of the European Geriatric Medicine Society
Subtitle of host publicationAdvancing Geriatric Medicine in a Modern World
PublisherElsevier
Publication statusPublished - 2018

Publication series

NameEuropean Geriatric Medicine
PublisherElsevier
ISSN (Print)1878-7649
ISSN (Electronic)1878-7657

Fingerprint

Xenobiotics
Antioxidants
Comorbidity
Drug-Related Side Effects and Adverse Reactions
Genes
Proteins
Transcription Factors
Polypharmacy
Messenger RNA
Real-Time Polymerase Chain Reaction
Rodentia
Blood Cells
Enzymes
Pharmaceutical Preparations
Therapeutics

Cite this

Scutt, G., Overall, A., Bakrania, P., Krasteva, E., Parekh, N., Ali, K., ... Rajkumar, C. (2018). Age-related changes to the expression of nuclear factor erythroid 2-like 2 (Nrf2), a regulatory antioxidant and xenobiotic defence gene. In 14th International Congress of the European Geriatric Medicine Society: Advancing Geriatric Medicine in a Modern World (European Geriatric Medicine). Elsevier.
Scutt, Greg ; Overall, Andrew ; Bakrania, Prijay ; Krasteva, Eliseveta ; Parekh, Nikesh ; Ali, Khalid ; Davies, Graham ; Rajkumar, Chakravarthi. / Age-related changes to the expression of nuclear factor erythroid 2-like 2 (Nrf2), a regulatory antioxidant and xenobiotic defence gene. 14th International Congress of the European Geriatric Medicine Society: Advancing Geriatric Medicine in a Modern World. Elsevier, 2018. (European Geriatric Medicine).
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Scutt, G, Overall, A, Bakrania, P, Krasteva, E, Parekh, N, Ali, K, Davies, G & Rajkumar, C 2018, Age-related changes to the expression of nuclear factor erythroid 2-like 2 (Nrf2), a regulatory antioxidant and xenobiotic defence gene. in 14th International Congress of the European Geriatric Medicine Society: Advancing Geriatric Medicine in a Modern World. European Geriatric Medicine, Elsevier.

Age-related changes to the expression of nuclear factor erythroid 2-like 2 (Nrf2), a regulatory antioxidant and xenobiotic defence gene. / Scutt, Greg; Overall, Andrew; Bakrania, Prijay; Krasteva, Eliseveta; Parekh, Nikesh; Ali, Khalid; Davies, Graham; Rajkumar, Chakravarthi.

14th International Congress of the European Geriatric Medicine Society: Advancing Geriatric Medicine in a Modern World. Elsevier, 2018. (European Geriatric Medicine).

Research output: Chapter in Book/Conference proceeding with ISSN or ISBNConference contribution with ISSN or ISBNResearchpeer-review

TY - GEN

T1 - Age-related changes to the expression of nuclear factor erythroid 2-like 2 (Nrf2), a regulatory antioxidant and xenobiotic defence gene

AU - Scutt, Greg

AU - Overall, Andrew

AU - Bakrania, Prijay

AU - Krasteva, Eliseveta

AU - Parekh, Nikesh

AU - Ali, Khalid

AU - Davies, Graham

AU - Rajkumar, Chakravarthi

PY - 2018

Y1 - 2018

N2 - Introduction Multimorbidity, polypharmacy and susceptibility to adverse drug reactions (ADR) are common problems in old age. Understanding the age-related biological changes that occur at a cellular level, may assist in identifying novel therapeutic targets. The nuclear factor erythroid 2-like 2 (Nrf2) transcription factor regulates antioxidant and drug metabolising pathways in the cell. Data from rodent models showed that Nrf2 protein expression declines with age. If similar findings are observed in humans, it may help to explain why older people are vulnerable to multimorbidity and ADRs. This study investigates whether Nrf2 expression (both mRNA and protein) decreases with increasing age in humans. Methods Fifty-five adults were recruited to our study (age range: 18-75 years). Participants donated 6 mL of venous blood, from which peripheral blood mononuclear cells (PBMCs) were separated and analysed for Nrf2 mRNA and protein expression (real time quantitative polymerase chain reaction and enzyme-linked immunosorbant assay respectively). Results Our data showed that Nrf2 protein expression was approximately 50% lower in individuals aged >30 years (0.065 ±0.014 EU <30 years vs. 0.033 ±0.0060 EU >30 years, p<0.05). Similarly, mRNA expression declined with advancing age (log2-fold change compared to 18-29 year-olds: 1.08±1.19, 2.14±1.25, -0.69±1.15, 0.45±2.03, -4.76±2.06, in 30-39, 40-49, 50-59, 60-69, >70 year age categories respectively; p<0.0001). Conclusions The expression of Nrf2 transcription factor is reduced in old age, potentially contributing to the increased risk of multimorbidity and adverse drug reactions.

AB - Introduction Multimorbidity, polypharmacy and susceptibility to adverse drug reactions (ADR) are common problems in old age. Understanding the age-related biological changes that occur at a cellular level, may assist in identifying novel therapeutic targets. The nuclear factor erythroid 2-like 2 (Nrf2) transcription factor regulates antioxidant and drug metabolising pathways in the cell. Data from rodent models showed that Nrf2 protein expression declines with age. If similar findings are observed in humans, it may help to explain why older people are vulnerable to multimorbidity and ADRs. This study investigates whether Nrf2 expression (both mRNA and protein) decreases with increasing age in humans. Methods Fifty-five adults were recruited to our study (age range: 18-75 years). Participants donated 6 mL of venous blood, from which peripheral blood mononuclear cells (PBMCs) were separated and analysed for Nrf2 mRNA and protein expression (real time quantitative polymerase chain reaction and enzyme-linked immunosorbant assay respectively). Results Our data showed that Nrf2 protein expression was approximately 50% lower in individuals aged >30 years (0.065 ±0.014 EU <30 years vs. 0.033 ±0.0060 EU >30 years, p<0.05). Similarly, mRNA expression declined with advancing age (log2-fold change compared to 18-29 year-olds: 1.08±1.19, 2.14±1.25, -0.69±1.15, 0.45±2.03, -4.76±2.06, in 30-39, 40-49, 50-59, 60-69, >70 year age categories respectively; p<0.0001). Conclusions The expression of Nrf2 transcription factor is reduced in old age, potentially contributing to the increased risk of multimorbidity and adverse drug reactions.

M3 - Conference contribution with ISSN or ISBN

T3 - European Geriatric Medicine

BT - 14th International Congress of the European Geriatric Medicine Society

PB - Elsevier

ER -

Scutt G, Overall A, Bakrania P, Krasteva E, Parekh N, Ali K et al. Age-related changes to the expression of nuclear factor erythroid 2-like 2 (Nrf2), a regulatory antioxidant and xenobiotic defence gene. In 14th International Congress of the European Geriatric Medicine Society: Advancing Geriatric Medicine in a Modern World. Elsevier. 2018. (European Geriatric Medicine).