Nicotinic acid improves mitochondrial function and associated transcriptional pathways in older inactive males
Nicotinic acid improves mitochondrial function and associated transcriptional pathways in older inactive males
Objectives: to examine the effect of the NAD + precursor, nicotinic acid (NA), for improving skeletal muscle status in sedentary older people.
Methods: in a double-blind, randomised, placebo-controlled design, 18 sedentary yet otherwise healthy older (65-75 y) males were assigned to 2-weeks of NA (acipimox; 250 mg × 3 daily, n=8) or placebo (PLA, n=10) supplementation. At baseline, and after week 1 and week 2 of supplementation, a battery of functional, metabolic, and molecular readouts were measured.
Results: resting and submaximal respiratory exchange ratio was lower (p<0.05) after 2 weeks in the NA group only, but maximal aerobic and anaerobic function and glucose handling were unchanged (p>0.05). Bayesian statistical modelling identified that leak, maximal coupled and maximal uncoupled mitochondrial respiratory states, increased over the 2-week supplemental period in the NA group (probability for a positive change (pd) 85.2, 90.8 and 95.9 %, respectively) but not in PLA. Citrate synthase and protein content of complex II (SDHB) and V (ATP5A) electron transport chain (ETC) components increased over the 2-week period in the NA group only (pd 95.1, 74.5 and 82.3 %, respectively). Mitochondrial and myofibrillar protein synthetic rates remained unchanged in both groups. NA intake altered the muscle transcriptome by increasing the expression of gene pathways related to cell adhesion/cytoskeleton organisation and inflammation/immunity and decreasing pathway expression of ETC and aerobic respiration processes. NAD +-specific pathways (e.g., de novo NAD + biosynthetic processes) and genes (e.g., NADSYN1) were uniquely regulated by NA.
Conclusions: NA might be an effective strategy for improving ageing muscle mitochondrial health.
277-294
Deane, Colleen S.
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Willis, Craig R.G.
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Gallagher, Iain J.
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Brook, Matthew S.
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Gharahdaghi, Nima
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Wylie, Lee J.
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Wilkinson, Daniel J.
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Smith, Kenneth
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Atherton, Philip J.
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Etheridge, Timothy
7e2a840e-e28f-4b54-ba02-dcad0561dfc4
25 November 2024
Deane, Colleen S.
3320532e-f411-4ea8-9a14-4a9f248da898
Willis, Craig R.G.
53d80517-a0a9-4fee-9cae-0870a7458804
Gallagher, Iain J.
dc144e9d-d0da-473f-b0c4-371a60246321
Brook, Matthew S.
8e9838f6-d1af-4901-83db-40dfa0c72423
Gharahdaghi, Nima
ebbe72f7-c67c-485e-a521-43f5b11286bf
Wylie, Lee J.
bc4b38fd-d1e2-4d89-85db-cfb800381cac
Wilkinson, Daniel J.
72380ed8-6660-40ce-acec-2d65ef3045c4
Smith, Kenneth
4bc77c16-88fb-450c-8c11-a1485339c08d
Atherton, Philip J.
b9c1604a-deaa-4174-8b72-e564dd72dd68
Etheridge, Timothy
7e2a840e-e28f-4b54-ba02-dcad0561dfc4
Deane, Colleen S., Willis, Craig R.G., Gallagher, Iain J., Brook, Matthew S., Gharahdaghi, Nima, Wylie, Lee J., Wilkinson, Daniel J., Smith, Kenneth, Atherton, Philip J. and Etheridge, Timothy
(2024)
Nicotinic acid improves mitochondrial function and associated transcriptional pathways in older inactive males.
Translational Exercise Biomedicine, 1 (3-4), .
(doi:10.1515/teb-2024-0030).
Abstract
Objectives: to examine the effect of the NAD + precursor, nicotinic acid (NA), for improving skeletal muscle status in sedentary older people.
Methods: in a double-blind, randomised, placebo-controlled design, 18 sedentary yet otherwise healthy older (65-75 y) males were assigned to 2-weeks of NA (acipimox; 250 mg × 3 daily, n=8) or placebo (PLA, n=10) supplementation. At baseline, and after week 1 and week 2 of supplementation, a battery of functional, metabolic, and molecular readouts were measured.
Results: resting and submaximal respiratory exchange ratio was lower (p<0.05) after 2 weeks in the NA group only, but maximal aerobic and anaerobic function and glucose handling were unchanged (p>0.05). Bayesian statistical modelling identified that leak, maximal coupled and maximal uncoupled mitochondrial respiratory states, increased over the 2-week supplemental period in the NA group (probability for a positive change (pd) 85.2, 90.8 and 95.9 %, respectively) but not in PLA. Citrate synthase and protein content of complex II (SDHB) and V (ATP5A) electron transport chain (ETC) components increased over the 2-week period in the NA group only (pd 95.1, 74.5 and 82.3 %, respectively). Mitochondrial and myofibrillar protein synthetic rates remained unchanged in both groups. NA intake altered the muscle transcriptome by increasing the expression of gene pathways related to cell adhesion/cytoskeleton organisation and inflammation/immunity and decreasing pathway expression of ETC and aerobic respiration processes. NAD +-specific pathways (e.g., de novo NAD + biosynthetic processes) and genes (e.g., NADSYN1) were uniquely regulated by NA.
Conclusions: NA might be an effective strategy for improving ageing muscle mitochondrial health.
Text
10.1515_teb-2024-0030 (1)
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Published date: 25 November 2024
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Local EPrints ID: 499448
URI: http://eprints.soton.ac.uk/id/eprint/499448
ISSN: 2942-6812
PURE UUID: 4a611387-1e8a-480b-ac7f-e0cfc842d8d2
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Date deposited: 20 Mar 2025 17:35
Last modified: 22 Aug 2025 02:36
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Contributors
Author:
Colleen S. Deane
Author:
Craig R.G. Willis
Author:
Iain J. Gallagher
Author:
Matthew S. Brook
Author:
Nima Gharahdaghi
Author:
Lee J. Wylie
Author:
Daniel J. Wilkinson
Author:
Kenneth Smith
Author:
Philip J. Atherton
Author:
Timothy Etheridge
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