NMN reverses D-galactose-induced neurodegeneration and enhances the intestinal barrier of mice by activating the Sirt1 pathway.

Lin Y, Wang Y, Yang X, Ding Z, Hu M, Huang X, Zhang Q, Yu Y

Frontiers in pharmacology10 Apr 2025Cited by 13 (Europe PMC)

PMID40276601PMCIDPMC12018880DOI10.3389/fphar.2025.1545585PepBankPUB-40276601

Summary

BackgroundAge-related decline in nicotinamide adenine dinucleotide (NAD+)-a central regulator of cellular metabolism, DNA repair, and immune homeostasis-is strongly associated with physiological dysfunction. Nicotinamide mononucleotide (NMN), a potent NAD+ precursor, shows promise in counteracting aging-related pathologies, particularly neurodegenerative decline.MethodsAn aging model was established in mice through 8-week D-galactose (D-gal) exposure, followed by NMN oral supplementation. Behavioral outcomes (open field test, Morris water maze) were analyzed alongside oxidative stress markers (SOD, CAT, AGEs), inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-10), and neurotransmitters (LC-MS/MS). Apoptotic activity (TUNEL, p16/p21), mitochondrial regulators (Sirt1, p-AMPK, PGC-1α), and intestinal barrier integrity (HE/AB-PAS staining) were evaluated. Sirt1 dependency was confirmed using inhibitor Ex527.ResultsNMN restored locomotor activity and spatial memory in D-gal mice without altering body weight. Mechanistically, NMN synergistically attenuated oxidative stress and systemic inflammation, elevating antioxidant enzymes (SOD, CAT) and IL-10 while suppressing pro-inflammatory cytokines (TNF-α, IL-6) and AGEs. Cortical/hippocampal analyses revealed reduced apoptosis (TUNEL⁺ cells) and senescence markers (p16, p21), with enhanced mitochondrial function via Sirt1/AMPK/PGC-1α activation (Sirt1, p-AMPK). NMN concurrently preserved intestinal mucosal architecture, mitigating D-gal-induced barrier disruption. Crucially, all benefits were abolished by Sirt1 inhibition, confirming pathway specificity.ConclusionOur findings establish NMN as a multifaceted therapeutic agent that preserves neurocognitive function and intestinal homeostasis in aging models by orchestrating antioxidative, anti-inflammatory, and antiapoptotic responses through Sirt1/AMPK/PGC-1α activation. This work provides translational insights into NAD+-boosting strategies for age-related disorders.

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

Results from this study20

19 results from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Efficacy outcome
In D-galactose-treated mice, NMN restored locomotor activity.
In plain wordsIn mice treated with D-galactose, NMN restored movement activity.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
IncreaseLocomotor activity
Study
mousen: not reported in source
D-galactose-induced aging
Outcome group
Exercise and physical function · Nervous system and cognition
Studied dose
Dose not stated · oralAs given in this study (mouse).
Source sentences
Summary
NMN restored locomotor activity and spatial memory in D-gal mice without altering body weight.
1 context sentence(design, population, supporting numbers)
Summary · context
An aging model was established in mice through 8-week D-galactose (D-gal) exposure, followed by NMN oral supplementation.
Show in the study text Report a problemFND-4027660101
02AnimalAnimal study (in vivo)Efficacy outcome
In D-galactose-treated mice, NMN restored spatial memory.
In plain wordsIn mice treated with D-galactose, NMN restored spatial memory.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
IncreaseSpatial memory
Study
mousen: not reported in source
D-galactose-induced aging
Outcome group
Cognition and memory · Nervous system and cognition
Studied dose
Dose not stated · oralAs given in this study (mouse).
Source sentences
Summary
NMN restored locomotor activity and spatial memory in D-gal mice without altering body weight.
1 context sentence(design, population, supporting numbers)
Summary · context
An aging model was established in mice through 8-week D-galactose (D-gal) exposure, followed by NMN oral supplementation.
Show in the study text Report a problemFND-4027660102
03AnimalAnimal study (in vivo)Efficacy outcome
In D-galactose-treated mice, NMN did not alter body weight.
In plain wordsIn mice treated with D-galactose, NMN did not change body weight.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
No significant changeBody weight
Study
mousen: not reported in source
D-galactose-induced aging
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated · oralAs given in this study (mouse).
Source sentences
Summary
NMN restored locomotor activity and spatial memory in D-gal mice without altering body weight.
1 context sentence(design, population, supporting numbers)
Summary · context
An aging model was established in mice through 8-week D-galactose (D-gal) exposure, followed by NMN oral supplementation.
Show in the study text Report a problemFND-4027660103
04AnimalAnimal study (in vivo)Efficacy outcome
In D-galactose-treated mice, NMN attenuated oxidative stress.
In plain wordsIn mice treated with D-galactose, NMN reduced oxidative stress.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseOxidative stress
Study
mousen: not reported in source
D-galactose-induced aging
Outcome group
Mitochondrial function · Nervous system and cognition
Studied dose
Dose not stated · oralAs given in this study (mouse).
Source sentences
Summary
Mechanistically, NMN synergistically attenuated oxidative stress and systemic inflammation, elevating antioxidant enzymes (SOD, CAT) and IL-10 while suppressing pro-inflammatory cytokines (TNF-α, IL-6) and AGEs.
1 context sentence(design, population, supporting numbers)
Summary · context
An aging model was established in mice through 8-week D-galactose (D-gal) exposure, followed by NMN oral supplementation.
Show in the study text Report a problemFND-4027660104
05AnimalAnimal study (in vivo)Efficacy outcome
In D-galactose-treated mice, NMN attenuated systemic inflammation.
In plain wordsIn mice treated with D-galactose, NMN reduced systemic inflammation.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseSystemic inflammation
Study
mousen: not reported in source
D-galactose-induced aging
Outcome group
Inflammation markers · Immune and inflammation
Studied dose
Dose not stated · oralAs given in this study (mouse).
Source sentences
Summary
Mechanistically, NMN synergistically attenuated oxidative stress and systemic inflammation, elevating antioxidant enzymes (SOD, CAT) and IL-10 while suppressing pro-inflammatory cytokines (TNF-α, IL-6) and AGEs.
1 context sentence(design, population, supporting numbers)
Summary · context
An aging model was established in mice through 8-week D-galactose (D-gal) exposure, followed by NMN oral supplementation.
Show in the study text Report a problemFND-4027660105
06AnimalAnimal study (in vivo)Efficacy outcome
In D-galactose-treated mice, NMN elevated SOD.
In plain wordsIn mice treated with D-galactose, NMN increased the antioxidant enzyme SOD.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
IncreaseSOD
Study
mousen: not reported in source
D-galactose-induced aging
Outcome group
Mitochondrial function · Nervous system and cognition
Studied dose
Dose not stated · oralAs given in this study (mouse).
Source sentences
Summary
Mechanistically, NMN synergistically attenuated oxidative stress and systemic inflammation, elevating antioxidant enzymes (SOD, CAT) and IL-10 while suppressing pro-inflammatory cytokines (TNF-α, IL-6) and AGEs.
1 context sentence(design, population, supporting numbers)
Summary · context
An aging model was established in mice through 8-week D-galactose (D-gal) exposure, followed by NMN oral supplementation.
Show in the study text Report a problemFND-4027660106
07AnimalAnimal study (in vivo)Efficacy outcome
In D-galactose-treated mice, NMN elevated CAT.
In plain wordsIn mice treated with D-galactose, NMN increased the antioxidant enzyme CAT.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
IncreaseCAT
Study
mousen: not reported in source
D-galactose-induced aging
Outcome group
Mitochondrial function · Nervous system and cognition
Studied dose
Dose not stated · oralAs given in this study (mouse).
Source sentences
Summary
Mechanistically, NMN synergistically attenuated oxidative stress and systemic inflammation, elevating antioxidant enzymes (SOD, CAT) and IL-10 while suppressing pro-inflammatory cytokines (TNF-α, IL-6) and AGEs.
1 context sentence(design, population, supporting numbers)
Summary · context
An aging model was established in mice through 8-week D-galactose (D-gal) exposure, followed by NMN oral supplementation.
Show in the study text Report a problemFND-4027660107
08AnimalAnimal study (in vivo)Efficacy outcome
In D-galactose-treated mice, NMN elevated IL-10.
In plain wordsIn mice treated with D-galactose, NMN increased IL-10.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
IncreaseIL-10
Study
mousen: not reported in source
D-galactose-induced aging
Outcome group
Inflammation markers · Immune and inflammation
Studied dose
Dose not stated · oralAs given in this study (mouse).
Source sentences
Summary
Mechanistically, NMN synergistically attenuated oxidative stress and systemic inflammation, elevating antioxidant enzymes (SOD, CAT) and IL-10 while suppressing pro-inflammatory cytokines (TNF-α, IL-6) and AGEs.
1 context sentence(design, population, supporting numbers)
Summary · context
An aging model was established in mice through 8-week D-galactose (D-gal) exposure, followed by NMN oral supplementation.
Show in the study text Report a problemFND-4027660108
09AnimalAnimal study (in vivo)Efficacy outcome
In D-galactose-treated mice, NMN suppressed TNF-α.
In plain wordsIn mice treated with D-galactose, NMN reduced TNF-α.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseTNF-α
Study
mousen: not reported in source
D-galactose-induced aging
Outcome group
Inflammation markers · Immune and inflammation
Studied dose
Dose not stated · oralAs given in this study (mouse).
Source sentences
Summary
Mechanistically, NMN synergistically attenuated oxidative stress and systemic inflammation, elevating antioxidant enzymes (SOD, CAT) and IL-10 while suppressing pro-inflammatory cytokines (TNF-α, IL-6) and AGEs.
1 context sentence(design, population, supporting numbers)
Summary · context
An aging model was established in mice through 8-week D-galactose (D-gal) exposure, followed by NMN oral supplementation.
Show in the study text Report a problemFND-4027660109
10AnimalAnimal study (in vivo)Efficacy outcome
In D-galactose-treated mice, NMN suppressed IL-6.
In plain wordsIn mice treated with D-galactose, NMN reduced IL-6.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseIL-6
Study
mousen: not reported in source
D-galactose-induced aging
Outcome group
Inflammation markers · Immune and inflammation
Studied dose
Dose not stated · oralAs given in this study (mouse).
Source sentences
Summary
Mechanistically, NMN synergistically attenuated oxidative stress and systemic inflammation, elevating antioxidant enzymes (SOD, CAT) and IL-10 while suppressing pro-inflammatory cytokines (TNF-α, IL-6) and AGEs.
1 context sentence(design, population, supporting numbers)
Summary · context
An aging model was established in mice through 8-week D-galactose (D-gal) exposure, followed by NMN oral supplementation.
Show in the study text Report a problemFND-4027660110
11AnimalAnimal study (in vivo)Efficacy outcome
In D-galactose-treated mice, NMN suppressed AGEs.
In plain wordsIn mice treated with D-galactose, NMN reduced advanced glycation end products.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseAGEs
Study
mousen: not reported in source
D-galactose-induced aging
Outcome group
Aging markers · Nervous system and cognition
Studied dose
Dose not stated · oralAs given in this study (mouse).
Source sentences
Summary
Mechanistically, NMN synergistically attenuated oxidative stress and systemic inflammation, elevating antioxidant enzymes (SOD, CAT) and IL-10 while suppressing pro-inflammatory cytokines (TNF-α, IL-6) and AGEs.
1 context sentence(design, population, supporting numbers)
Summary · context
An aging model was established in mice through 8-week D-galactose (D-gal) exposure, followed by NMN oral supplementation.
Show in the study text Report a problemFND-4027660111
12AnimalAnimal study (in vivo)Efficacy outcome
In D-galactose-treated mice, NMN reduced cortical and hippocampal apoptosis measured by TUNEL-positive cells.
In plain wordsIn mice treated with D-galactose, NMN reduced programmed cell death in the cortex and hippocampus.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseCortical and hippocampal apoptosis
Study
mousen: not reported in source
D-galactose-induced aging
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
Dose not stated · oralAs given in this study (mouse).
Source sentences
Summary
Cortical/hippocampal analyses revealed reduced apoptosis (TUNEL⁺ cells) and senescence markers (p16, p21), with enhanced mitochondrial function via Sirt1/AMPK/PGC-1α activation (Sirt1, p-AMPK).
1 context sentence(design, population, supporting numbers)
Summary · context
An aging model was established in mice through 8-week D-galactose (D-gal) exposure, followed by NMN oral supplementation.
Show in the study text Report a problemFND-4027660112
13AnimalAnimal study (in vivo)Efficacy outcome
In D-galactose-treated mice, NMN reduced cortical and hippocampal p16 senescence markers.
In plain wordsIn mice treated with D-galactose, NMN reduced the senescence marker p16 in the cortex and hippocampus.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
Decreasep16
Study
mousen: not reported in source
D-galactose-induced aging
Outcome group
Aging markers · Nervous system and cognition
Studied dose
Dose not stated · oralAs given in this study (mouse).
Source sentences
Summary
Cortical/hippocampal analyses revealed reduced apoptosis (TUNEL⁺ cells) and senescence markers (p16, p21), with enhanced mitochondrial function via Sirt1/AMPK/PGC-1α activation (Sirt1, p-AMPK).
1 context sentence(design, population, supporting numbers)
Summary · context
An aging model was established in mice through 8-week D-galactose (D-gal) exposure, followed by NMN oral supplementation.
Show in the study text Report a problemFND-4027660113
14AnimalAnimal study (in vivo)Efficacy outcome
In D-galactose-treated mice, NMN reduced cortical and hippocampal p21 senescence markers.
In plain wordsIn mice treated with D-galactose, NMN reduced the senescence marker p21 in the cortex and hippocampus.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
Decreasep21
Study
mousen: not reported in source
D-galactose-induced aging
Outcome group
Aging markers · Nervous system and cognition
Studied dose
Dose not stated · oralAs given in this study (mouse).
Source sentences
Summary
Cortical/hippocampal analyses revealed reduced apoptosis (TUNEL⁺ cells) and senescence markers (p16, p21), with enhanced mitochondrial function via Sirt1/AMPK/PGC-1α activation (Sirt1, p-AMPK).
1 context sentence(design, population, supporting numbers)
Summary · context
An aging model was established in mice through 8-week D-galactose (D-gal) exposure, followed by NMN oral supplementation.
Show in the study text Report a problemFND-4027660114
15AnimalAnimal study (in vivo)Efficacy outcome
In D-galactose-treated mice, NMN enhanced cortical and hippocampal mitochondrial function through Sirt1/AMPK/PGC-1α activation.
In plain wordsIn mice treated with D-galactose, NMN improved mitochondrial function through Sirt1/AMPK/PGC-1α activation.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
IncreaseMitochondrial function
Study
mousen: not reported in source
D-galactose-induced aging
Outcome group
Mitochondrial function · Nervous system and cognition
Studied dose
Dose not stated · oralAs given in this study (mouse).
Source sentences
Summary
Cortical/hippocampal analyses revealed reduced apoptosis (TUNEL⁺ cells) and senescence markers (p16, p21), with enhanced mitochondrial function via Sirt1/AMPK/PGC-1α activation (Sirt1, p-AMPK).
1 context sentence(design, population, supporting numbers)
Summary · context
An aging model was established in mice through 8-week D-galactose (D-gal) exposure, followed by NMN oral supplementation.
Show in the study text Report a problemFND-4027660115
16AnimalAnimal study (in vivo)Mechanism
In D-galactose-treated mice, NMN enhanced Sirt1 activation in cortical and hippocampal analyses.
In plain wordsIn mice treated with D-galactose, NMN increased Sirt1 activation in the cortex and hippocampus.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
IncreaseSirt1 activation
Study
mousen: not reported in source
D-galactose-induced aging
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Studied dose
Dose not stated · oralAs given in this study (mouse).
Source sentences
Summary
Cortical/hippocampal analyses revealed reduced apoptosis (TUNEL⁺ cells) and senescence markers (p16, p21), with enhanced mitochondrial function via Sirt1/AMPK/PGC-1α activation (Sirt1, p-AMPK).
1 context sentence(design, population, supporting numbers)
Summary · context
An aging model was established in mice through 8-week D-galactose (D-gal) exposure, followed by NMN oral supplementation.
Show in the study text Report a problemFND-4027660116
17AnimalAnimal study (in vivo)Mechanism
In D-galactose-treated mice, NMN enhanced AMPK activation indicated by p-AMPK.
In plain wordsIn mice treated with D-galactose, NMN increased AMPK activation, indicated by p-AMPK.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
Increasep-AMPK
Study
mousen: not reported in source
D-galactose-induced aging
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Studied dose
Dose not stated · oralAs given in this study (mouse).
Source sentences
Summary
Cortical/hippocampal analyses revealed reduced apoptosis (TUNEL⁺ cells) and senescence markers (p16, p21), with enhanced mitochondrial function via Sirt1/AMPK/PGC-1α activation (Sirt1, p-AMPK).
1 context sentence(design, population, supporting numbers)
Summary · context
An aging model was established in mice through 8-week D-galactose (D-gal) exposure, followed by NMN oral supplementation.
Show in the study text Report a problemFND-4027660117
18AnimalAnimal study (in vivo)Efficacy outcome
In D-galactose-treated mice, NMN preserved intestinal mucosal architecture and mitigated barrier disruption.
In plain wordsIn mice treated with D-galactose, NMN preserved intestinal structure and reduced barrier disruption.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
MixedIntestinal mucosal architecture and barrier
Study
mousen: not reported in source
D-galactose-induced aging
Outcome group
Gastrointestinal protection · Gastrointestinal
Studied dose
Dose not stated · oralAs given in this study (mouse).
Source sentences
Summary
NMN concurrently preserved intestinal mucosal architecture, mitigating D-gal-induced barrier disruption.
1 context sentence(design, population, supporting numbers)
Summary · context
An aging model was established in mice through 8-week D-galactose (D-gal) exposure, followed by NMN oral supplementation.
Show in the study text Report a problemFND-4027660118
19AnimalAnimal study (in vivo)Mechanism
In D-galactose-treated mice, NMN enhanced cortical and hippocampal mitochondrial function through Sirt1/AMPK/PGC-1α activation.
In plain wordsIn mice treated with D-galactose, NMN activated the Sirt1/AMPK/PGC-1α pathway in the cortex and hippocampus.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
IncreasePGC-1α activation
Study
mousen: not reported in source
D-galactose-induced aging
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Studied dose
Dose not stated · oralAs given in this study (mouse).
Source sentences
Summary
Cortical/hippocampal analyses revealed reduced apoptosis (TUNEL⁺ cells) and senescence markers (p16, p21), with enhanced mitochondrial function via Sirt1/AMPK/PGC-1α activation (Sirt1, p-AMPK).
1 context sentence(design, population, supporting numbers)
Summary · context
An aging model was established in mice through 8-week D-galactose (D-gal) exposure, followed by NMN oral supplementation.
Show in the study text Report a problemFND-4027660120

Studies that did not test the peptide alone1

In this study, NMN (nicotinamide mononucleotide) 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 NMN (nicotinamide mononucleotide).

20AnimalNot a test of NMN (nicotinamide mononucleotide) aloneAnimal study (in vivo)Mechanism
In D-galactose-treated mice, Sirt1 inhibition abolished all reported NMN benefits.
In plain wordsIn mice treated with D-galactose, blocking Sirt1 abolished all reported NMN benefits.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
Not applicableSirt1 dependence of benefits
Study
mousen: not reported in source
D-galactose-induced aging
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Source sentences
Summary
Crucially, all benefits were abolished by Sirt1 inhibition, confirming pathway specificity.
2 context sentences(design, population, supporting numbers)
Summary · context
Sirt1 dependency was confirmed using inhibitor Ex527.
Summary · context
An aging model was established in mice through 8-week D-galactose (D-gal) exposure, followed by NMN oral supplementation.
In this study, NMN (nicotinamide mononucleotide) 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 NMN (nicotinamide mononucleotide).
Show in the study text Report a problemFND-4027660119

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
21 Oct 2026, 15:58 UTC
Study results updated
Version 1
21 Oct 2026, 12:50 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

Publication types

Keywords

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