Long-term NAD+ supplementation prevents the progression of age-related hearing loss in mice.

Okur MN, Sahbaz BD, Kimura R, Manor U, Patel J, Park JH, Andrade L, Puligilla C, Croteau DL, Bohr VA

Aging cell3 Jul 2023Cited by 36 (Europe PMC)

PMID37395319PMCIDPMC10497810DOI10.1111/acel.13909PepBankPUB-37395319

Summary

Age-related hearing loss (ARHL) is the most common sensory disability associated with human aging. Yet, there are no approved measures for preventing or treating this debilitating condition. With its slow progression, continuous and safe approaches are critical for ARHL treatment. Nicotinamide Riboside (NR), a NAD+ precursor, is well tolerated even for long-term use and is already shown effective in various disease models including Alzheimer's and Parkinson's disease. It has also been beneficial against noise-induced hearing loss and in hearing loss associated with premature aging. However, its beneficial impact on ARHL is not known. Using two different wild-type mouse strains, we show that long-term NR administration prevents the progression of ARHL. Through transcriptomic and biochemical analysis, we find that NR administration restores age-associated reduction in cochlear NAD+ levels, upregulates biological pathways associated with synaptic transmission and PPAR signaling, and reduces the number of orphan ribbon synapses between afferent auditory neurons and inner hair cells. We also find that NR targets a novel pathway of lipid droplets in the cochlea by inducing the expression of CIDEC and PLIN1 proteins that are downstream of PPAR signaling and are key for lipid droplet growth. Taken together, our results demonstrate the therapeutic potential of NR treatment for ARHL and provide novel insights into its mechanism of action.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study7

No result from this study comes from a test of the peptide.

Natural levels measured1

These results measure the body's own peptide. Nobody was given the peptide. They are not evidence about taking it. They are left out of key results, evidence counts and charts.

01AnimalEndogenous levelAnimal study (in vivo)Mechanism
In mice, NR restored the age-associated reduction in cochlear NAD+ levels.
In plain wordsIn mice, NR restored the body's own cochlear NAD+ levels that had decreased with age.
Peptide
NAD+ (nicotinamide adenine dinucleotide)
Outcome
IncreaseCochlear NAD+ levels
Study
mousen: not reported in source
Wild-type mouse strains
Outcome group
Mitochondrial function · Pharmacology
Source sentences
Summary
Through transcriptomic and biochemical analysis, we find that NR administration restores age-associated reduction in cochlear NAD+ levels
1 context sentence(design, population, supporting numbers)
Summary · context
Using two different wild-type mouse strains, we show that long-term NR administration prevents the progression of ARHL.
This result measures the body's own NAD+ (nicotinamide adenine dinucleotide). Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3739531902

Studies that did not test the peptide alone6

In this study, NAD+ (nicotinamide adenine dinucleotide) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking NAD+ (nicotinamide adenine dinucleotide).

02AnimalNot a test of NAD+ (nicotinamide adenine dinucleotide) aloneAnimal study (in vivo)Efficacy outcome
In wild-type mice, long-term NR administration prevented age-related hearing loss progression.
In plain wordsIn mice, NR prevented the progression of age-related hearing loss.
Peptide
NAD+ (nicotinamide adenine dinucleotide)
Outcome
DecreaseAge-related hearing loss progression
Study
mousen: not reported in source
Wild-type mouse strains
Outcome group
Sensory perception · Nervous system and cognition
Source sentences
Summary
Using two different wild-type mouse strains, we show that long-term NR administration prevents the progression of ARHL.
In this study, NAD+ (nicotinamide adenine dinucleotide) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking NAD+ (nicotinamide adenine dinucleotide).
Show in the study text Report a problemFND-3739531901
03AnimalNot a test of NAD+ (nicotinamide adenine dinucleotide) aloneAnimal study (in vivo)Mechanism
In mice, NR increased biological pathways associated with synaptic transmission.
In plain wordsIn mice, NR increased pathways associated with synaptic transmission.
Peptide
NAD+ (nicotinamide adenine dinucleotide)
Outcome
IncreaseSynaptic transmission pathways
Study
mousen: not reported in source
Wild-type mouse strains
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Source sentences
Summary
upregulates biological pathways associated with synaptic transmission and PPAR signaling
1 context sentence(design, population, supporting numbers)
Summary · context
Using two different wild-type mouse strains, we show that long-term NR administration prevents the progression of ARHL.
In this study, NAD+ (nicotinamide adenine dinucleotide) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking NAD+ (nicotinamide adenine dinucleotide).
Show in the study text Report a problemFND-3739531903
04AnimalNot a test of NAD+ (nicotinamide adenine dinucleotide) aloneAnimal study (in vivo)Mechanism
In mice, NR increased biological pathways associated with PPAR signaling.
In plain wordsIn mice, NR increased pathways associated with PPAR signaling.
Peptide
NAD+ (nicotinamide adenine dinucleotide)
Outcome
IncreasePPAR signaling pathways
Study
mousen: not reported in source
Wild-type mouse strains
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Source sentences
Summary
upregulates biological pathways associated with synaptic transmission and PPAR signaling
1 context sentence(design, population, supporting numbers)
Summary · context
Using two different wild-type mouse strains, we show that long-term NR administration prevents the progression of ARHL.
In this study, NAD+ (nicotinamide adenine dinucleotide) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking NAD+ (nicotinamide adenine dinucleotide).
Show in the study text Report a problemFND-3739531904
05AnimalNot a test of NAD+ (nicotinamide adenine dinucleotide) aloneAnimal study (in vivo)Mechanism
In mice, NR reduced orphan ribbon synapses between afferent auditory neurons and inner hair cells.
In plain wordsIn mice, NR reduced orphan ribbon synapses between auditory neurons and inner hair cells.
Peptide
NAD+ (nicotinamide adenine dinucleotide)
Outcome
DecreaseOrphan ribbon synapses
Study
mousen: not reported in source
Wild-type mouse strains
Outcome group
Neuroprotection · Nervous system and cognition
Source sentences
Summary
and reduces the number of orphan ribbon synapses between afferent auditory neurons and inner hair cells.
1 context sentence(design, population, supporting numbers)
Summary · context
Using two different wild-type mouse strains, we show that long-term NR administration prevents the progression of ARHL.
In this study, NAD+ (nicotinamide adenine dinucleotide) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking NAD+ (nicotinamide adenine dinucleotide).
Show in the study text Report a problemFND-3739531905
06AnimalNot a test of NAD+ (nicotinamide adenine dinucleotide) aloneAnimal study (in vivo)Mechanism
In mice, NR induced cochlear CIDEC protein expression downstream of PPAR signaling.
In plain wordsIn mice, NR increased cochlear CIDEC protein expression.
Peptide
NAD+ (nicotinamide adenine dinucleotide)
Outcome
IncreaseCIDEC expression
Study
mousen: not reported in source
Wild-type mouse strains
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Source sentences
Summary
We also find that NR targets a novel pathway of lipid droplets in the cochlea by inducing the expression of CIDEC and PLIN1 proteins that are downstream of PPAR signaling and are key for lipid droplet growth.
1 context sentence(design, population, supporting numbers)
Summary · context
Using two different wild-type mouse strains, we show that long-term NR administration prevents the progression of ARHL.
In this study, NAD+ (nicotinamide adenine dinucleotide) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking NAD+ (nicotinamide adenine dinucleotide).
Show in the study text Report a problemFND-3739531906
07AnimalNot a test of NAD+ (nicotinamide adenine dinucleotide) aloneAnimal study (in vivo)Mechanism
In mice, NR induced cochlear PLIN1 protein expression downstream of PPAR signaling.
In plain wordsIn mice, NR increased cochlear PLIN1 protein expression.
Peptide
NAD+ (nicotinamide adenine dinucleotide)
Outcome
IncreasePLIN1 expression
Study
mousen: not reported in source
Wild-type mouse strains
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Source sentences
Summary
We also find that NR targets a novel pathway of lipid droplets in the cochlea by inducing the expression of CIDEC and PLIN1 proteins that are downstream of PPAR signaling and are key for lipid droplet growth.
1 context sentence(design, population, supporting numbers)
Summary · context
Using two different wild-type mouse strains, we show that long-term NR administration prevents the progression of ARHL.
In this study, NAD+ (nicotinamide adenine dinucleotide) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking NAD+ (nicotinamide adenine dinucleotide).
Show in the study text Report a problemFND-3739531907

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
14 Oct 2026, 05:02 UTC
Study results updated
Version 1
14 Oct 2026, 01:46 UTC
First added · source update from Europe PMC

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