The duration of lithium use and biological ageing: telomere length, frailty, metabolomic age and all-cause mortality

Julian Mutz; Win Lee Edwin Wong; Timothy Powell; Allan Young; Gavin S. Dawe; Cathryn Lewis

doi:10.1007/s11357-024-01142-y

The duration of lithium use and biological ageing: telomere length, frailty, metabolomic age and all-cause mortality

Julian Mutz^*, Win Lee Edwin Wong, Timothy Powell, Allan Young, Gavin S. Dawe, Cathryn Lewis

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

1 Citation (Scopus)

Abstract

Lithium is an established first-line treatment for bipolar disorder. Beyond its therapeutic effect as a mood stabiliser, lithium exhibits potential anti-ageing effects. This study aimed to examine the relationship between the duration of lithium use, biological ageing and mortality. The UK Biobank is an observational study of middle-aged and older adults. We tested associations between the duration of lithium use (number of prescriptions, total duration of use and duration of the first prescription period) and telomere length, frailty, metabolomic age (MileAge) delta, pulse rate and all-cause mortality. Five hundred ninety-one individuals (mean age = 57.49 years; 55% females) had been prescribed lithium. There was no evidence that the number of prescriptions (β = − 0.022, 95% CI − 0.081 to 0.037, p = 0.47), the total duration of use (β = − 0.005, 95% CI − 0.023 to 0.013, p = 0.57) or the duration of the first prescription period (β = − 0.018, 95% CI − 0.051 to 0.015, p = 0.29) correlated with telomere length. There was also no evidence that the duration of lithium use correlated with frailty or MileAge delta. However, a higher prescription count and a longer duration of use was associated with a lower pulse rate. The duration of lithium use did not predict all-cause mortality. We observed no evidence of associations between the duration of lithium use and biological ageing markers, including telomere length. Our findings suggest that the potential anti-ageing effects of lithium do not differ by the duration of use.

Original language	English
Pages (from-to)	5981-5994
Number of pages	14
Journal	GeroScience
Volume	46
Issue number	6
DOIs	https://doi.org/10.1007/s11357-024-01142-y
Publication status	Published - 28 Mar 2024

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@article{3b111392326f44debcf2d97736ec48a2,

title = "The duration of lithium use and biological ageing: telomere length, frailty, metabolomic age and all-cause mortality",

abstract = "Lithium is an established first-line treatment for bipolar disorder. Beyond its therapeutic effect as a mood stabiliser, lithium exhibits potential anti-ageing effects. This study aimed to examine the relationship between the duration of lithium use, biological ageing and mortality. The UK Biobank is an observational study of middle-aged and older adults. We tested associations between the duration of lithium use (number of prescriptions, total duration of use and duration of the first prescription period) and telomere length, frailty, metabolomic age (MileAge) delta, pulse rate and all-cause mortality. Five hundred ninety-one individuals (mean age = 57.49 years; 55% females) had been prescribed lithium. There was no evidence that the number of prescriptions (β = − 0.022, 95% CI − 0.081 to 0.037, p = 0.47), the total duration of use (β = − 0.005, 95% CI − 0.023 to 0.013, p = 0.57) or the duration of the first prescription period (β = − 0.018, 95% CI − 0.051 to 0.015, p = 0.29) correlated with telomere length. There was also no evidence that the duration of lithium use correlated with frailty or MileAge delta. However, a higher prescription count and a longer duration of use was associated with a lower pulse rate. The duration of lithium use did not predict all-cause mortality. We observed no evidence of associations between the duration of lithium use and biological ageing markers, including telomere length. Our findings suggest that the potential anti-ageing effects of lithium do not differ by the duration of use.",

author = "Julian Mutz and Wong, {Win Lee Edwin} and Timothy Powell and Allan Young and Dawe, {Gavin S.} and Cathryn Lewis",

note = "Funding Information: AHY declares the following: paid lectures and advisory boards for companies with drugs used in affective and related disorders (Flow Neuroscience, Novartis, Roche, Janssen, Takeda, Noema pharma, Compass, Astrazenaca, Boehringer Ingelheim, Eli Lilly, LivaNova, Lundbeck, Sunovion, Servier, Livanova, Janssen, Allegan, Bionomics, Sumitomo Dainippon Pharma, Sage and Neurocentrx); principal investigator in the Restore-Life VNS registry study funded by LivaNova; principal investigator on “ESKETINTRD3004: An Open-label, Long-term, Safety and Efficacy Study of Intranasal Esketamine in Treatment-resistant Depression”; principal investigator on “The Effects of Psilocybin on Cognitive Function in Healthy Participants”; principal investigator on “The Safety and Efficacy of Psilocybin in Participants with Treatment-Resistant Depression (P-TRD)”; principal investigator on “A Double-Blind, Randomized, Parallel-Group Study with Quetiapine Extended Release as Comparator to Evaluate the Efficacy and Safety of Seltorexant 20 mg as Adjunctive Therapy to Antidepressants in Adult and Elderly Patients with Major Depressive Disorder with Insomnia Symptoms Who Have Responded Inadequately to Antidepressant Therapy” (Janssen); principal investigator on “An Open-label, Long-term, Safety and Efficacy Study of Aticaprant as Adjunctive Therapy in Adult and Elderly Participants with Major Depressive Disorder (MDD)” (Janssen); principal investigator on “A Randomized, Double-blind, Multicentre, Parallel-group, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Aticaprant 10 mg as Adjunctive Therapy in Adult Participants with Major Depressive Disorder (MDD) with Moderate-to-severe Anhedonia and Inadequate Response to Current Antidepressant Therapy”; principal investigator on “A Study of Disease Characteristics and Real-life Standard of Care Effectiveness in Patients with Major Depressive Disorder (MDD) With Anhedonia and Inadequate Response to Current Antidepressant Therapy Including an SSRI or SNR” (Janssen); UK chief investigator for Compass COMP006 & COMP007 studies; UK chief investigator for Novartis MDD study MIJ821A12201; grant funding (past and present) from NIMH (USA), CIHR (Canada), NARSAD (USA), Stanley Medical Research Institute (USA), MRC (UK), Wellcome Trust (UK), Royal College of Physicians (Edin), BMA (UK), UBC-VGH Foundation (Canada), WEDC (Canada), CCS Depression Research Fund (Canada), MSFHR (Canada), NIHR (UK), Janssen (UK) and EU Horizon 2020. No shareholdings in pharmaceutical companies. CML sits on the scientific advisory board for Myriad Neuroscience and has received speaker fees from SYNLAB and consultancy fees from UCB. JM, WLEW, TRP and GSD declare no financial conflict of interest. Funding Information: This study was funded by the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King{\textquoteright}s College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. WLEW is supported by the National University of Singapore President{\textquoteright}s Graduate Fellowship. TRP is supported by the MRC (UKRI) as part of a New Investigator Research Grant (MR/W028018/1). GSD is supported by the Ministry of Education, Singapore, under its Academic Research Fund Tier 3 Award (MOE2017-T3-1-002). This research has been conducted using data from UK Biobank, a major biomedical database. Data access permission has been granted under UK Biobank application 45514. All analyses were supported by: King{\textquoteright}s College London (2023). King{\textquoteright}s Computational Research, Engineering and Technology Environment (CREATE). Retrieved May 24, 2023, from https://doi.org/10.18742/rnvf-m076 Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

month = mar,

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doi = "10.1007/s11357-024-01142-y",

language = "English",

volume = "46",

pages = "5981--5994",

journal = "GeroScience",

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TY - JOUR

T1 - The duration of lithium use and biological ageing: telomere length, frailty, metabolomic age and all-cause mortality

AU - Mutz, Julian

AU - Wong, Win Lee Edwin

AU - Powell, Timothy

AU - Young, Allan

AU - Dawe, Gavin S.

AU - Lewis, Cathryn

N1 - Funding Information: AHY declares the following: paid lectures and advisory boards for companies with drugs used in affective and related disorders (Flow Neuroscience, Novartis, Roche, Janssen, Takeda, Noema pharma, Compass, Astrazenaca, Boehringer Ingelheim, Eli Lilly, LivaNova, Lundbeck, Sunovion, Servier, Livanova, Janssen, Allegan, Bionomics, Sumitomo Dainippon Pharma, Sage and Neurocentrx); principal investigator in the Restore-Life VNS registry study funded by LivaNova; principal investigator on “ESKETINTRD3004: An Open-label, Long-term, Safety and Efficacy Study of Intranasal Esketamine in Treatment-resistant Depression”; principal investigator on “The Effects of Psilocybin on Cognitive Function in Healthy Participants”; principal investigator on “The Safety and Efficacy of Psilocybin in Participants with Treatment-Resistant Depression (P-TRD)”; principal investigator on “A Double-Blind, Randomized, Parallel-Group Study with Quetiapine Extended Release as Comparator to Evaluate the Efficacy and Safety of Seltorexant 20 mg as Adjunctive Therapy to Antidepressants in Adult and Elderly Patients with Major Depressive Disorder with Insomnia Symptoms Who Have Responded Inadequately to Antidepressant Therapy” (Janssen); principal investigator on “An Open-label, Long-term, Safety and Efficacy Study of Aticaprant as Adjunctive Therapy in Adult and Elderly Participants with Major Depressive Disorder (MDD)” (Janssen); principal investigator on “A Randomized, Double-blind, Multicentre, Parallel-group, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Aticaprant 10 mg as Adjunctive Therapy in Adult Participants with Major Depressive Disorder (MDD) with Moderate-to-severe Anhedonia and Inadequate Response to Current Antidepressant Therapy”; principal investigator on “A Study of Disease Characteristics and Real-life Standard of Care Effectiveness in Patients with Major Depressive Disorder (MDD) With Anhedonia and Inadequate Response to Current Antidepressant Therapy Including an SSRI or SNR” (Janssen); UK chief investigator for Compass COMP006 & COMP007 studies; UK chief investigator for Novartis MDD study MIJ821A12201; grant funding (past and present) from NIMH (USA), CIHR (Canada), NARSAD (USA), Stanley Medical Research Institute (USA), MRC (UK), Wellcome Trust (UK), Royal College of Physicians (Edin), BMA (UK), UBC-VGH Foundation (Canada), WEDC (Canada), CCS Depression Research Fund (Canada), MSFHR (Canada), NIHR (UK), Janssen (UK) and EU Horizon 2020. No shareholdings in pharmaceutical companies. CML sits on the scientific advisory board for Myriad Neuroscience and has received speaker fees from SYNLAB and consultancy fees from UCB. JM, WLEW, TRP and GSD declare no financial conflict of interest. Funding Information: This study was funded by the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. WLEW is supported by the National University of Singapore President’s Graduate Fellowship. TRP is supported by the MRC (UKRI) as part of a New Investigator Research Grant (MR/W028018/1). GSD is supported by the Ministry of Education, Singapore, under its Academic Research Fund Tier 3 Award (MOE2017-T3-1-002). This research has been conducted using data from UK Biobank, a major biomedical database. Data access permission has been granted under UK Biobank application 45514. All analyses were supported by: King’s College London (2023). King’s Computational Research, Engineering and Technology Environment (CREATE). Retrieved May 24, 2023, from https://doi.org/10.18742/rnvf-m076 Publisher Copyright: © The Author(s) 2024.

PY - 2024/3/28

Y1 - 2024/3/28

N2 - Lithium is an established first-line treatment for bipolar disorder. Beyond its therapeutic effect as a mood stabiliser, lithium exhibits potential anti-ageing effects. This study aimed to examine the relationship between the duration of lithium use, biological ageing and mortality. The UK Biobank is an observational study of middle-aged and older adults. We tested associations between the duration of lithium use (number of prescriptions, total duration of use and duration of the first prescription period) and telomere length, frailty, metabolomic age (MileAge) delta, pulse rate and all-cause mortality. Five hundred ninety-one individuals (mean age = 57.49 years; 55% females) had been prescribed lithium. There was no evidence that the number of prescriptions (β = − 0.022, 95% CI − 0.081 to 0.037, p = 0.47), the total duration of use (β = − 0.005, 95% CI − 0.023 to 0.013, p = 0.57) or the duration of the first prescription period (β = − 0.018, 95% CI − 0.051 to 0.015, p = 0.29) correlated with telomere length. There was also no evidence that the duration of lithium use correlated with frailty or MileAge delta. However, a higher prescription count and a longer duration of use was associated with a lower pulse rate. The duration of lithium use did not predict all-cause mortality. We observed no evidence of associations between the duration of lithium use and biological ageing markers, including telomere length. Our findings suggest that the potential anti-ageing effects of lithium do not differ by the duration of use.

AB - Lithium is an established first-line treatment for bipolar disorder. Beyond its therapeutic effect as a mood stabiliser, lithium exhibits potential anti-ageing effects. This study aimed to examine the relationship between the duration of lithium use, biological ageing and mortality. The UK Biobank is an observational study of middle-aged and older adults. We tested associations between the duration of lithium use (number of prescriptions, total duration of use and duration of the first prescription period) and telomere length, frailty, metabolomic age (MileAge) delta, pulse rate and all-cause mortality. Five hundred ninety-one individuals (mean age = 57.49 years; 55% females) had been prescribed lithium. There was no evidence that the number of prescriptions (β = − 0.022, 95% CI − 0.081 to 0.037, p = 0.47), the total duration of use (β = − 0.005, 95% CI − 0.023 to 0.013, p = 0.57) or the duration of the first prescription period (β = − 0.018, 95% CI − 0.051 to 0.015, p = 0.29) correlated with telomere length. There was also no evidence that the duration of lithium use correlated with frailty or MileAge delta. However, a higher prescription count and a longer duration of use was associated with a lower pulse rate. The duration of lithium use did not predict all-cause mortality. We observed no evidence of associations between the duration of lithium use and biological ageing markers, including telomere length. Our findings suggest that the potential anti-ageing effects of lithium do not differ by the duration of use.

UR - http://www.scopus.com/inward/record.url?scp=85188838128&partnerID=8YFLogxK

U2 - 10.1007/s11357-024-01142-y

DO - 10.1007/s11357-024-01142-y

M3 - Article

VL - 46

SP - 5981

EP - 5994

JO - GeroScience

JF - GeroScience

IS - 6

ER -

The duration of lithium use and biological ageing: telomere length, frailty, metabolomic age and all-cause mortality

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