Nicotinamide Mononucleotide (NMN) Improves the Senescence of Mouse Vascular Smooth Muscle Cells Induced by Ang II Through Activating p-AMPK/KLF4 Pathway.

Liang N, Liu S, Wang Y, Ying L, Zhang K, Li H, Xiao L, Hu Y, Luo G

Pharmaceuticals (Basel, Switzerland)9 Apr 2025Cited by 5 (Europe PMC)

PMID40283988PMCIDPMC12030317DOI10.3390/ph18040553PepBankPUB-40283988

Summary

Background: Vascular smooth muscle cells (VSMCs) senescence exacerbates vascular diseases like atherosclerosis and hypertension. Angiotensin II (Ang II) is a strong inducer of VSMCs senescence, causing vascular damage, though its exact mechanism is unclear. Nicotinamide mononucleotide (NMN), a NAD⁺ precursor, has gained attention for its anti-senescence potential, yet its role in inhibiting VSMCs senescence is not fully understood. Methods: This study assessed senescence markers, including β-galactosidase activity (SA-β-gal) and the senescence-associated secretory phenotype (SASP), in mouse VSMCs treated with Ang II alone or with NMN and relevant activators/inhibitors. Results: Compared to controls, SA-β-gal levels and SASP secretion significantly increased in Ang II-exposed cells. In contrast, NMN reduced the expression of both markers. NMN also reversed Ang II-induced VSMCs senescence by downregulating KLF4 and p16 through AMPK activation, which Ang II inhibited, while decreasing mRNA levels of key SASP components. The effects of the AMPK activator AICAR were similar to those of NMN, whereas the AMPK inhibitor Compound C negated NMN's effects. Conclusions: In summary, NMN mitigates Ang II-induced mouse VSMCs senescence via the AMPK/KLF4/p16 pathway. This study underscores the anti-senescence effects of NMN on mouse VSMCs, supporting further exploration of its potential as a food supplement for preventing and treating vascular senescence.

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

Results from this study9

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

01LabIn vitro (cells)Mechanism
In mouse VSMCs, NMN reduced the senescence-associated β-galactosidase marker elevated by Ang II.
In plain wordsIn cells from mice, NMN reduced a cellular aging marker compared with Ang II alone.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseSA-β-gal expression
Study
mousen: not reported in source
Ang II-exposed vascular smooth muscle cells
Comparator
Ang II alone
Outcome group
Aging markers · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
In contrast, NMN reduced the expression of both markers.
2 context sentences(design, population, supporting numbers)
Summary · context
Compared to controls, SA-β-gal levels and SASP secretion significantly increased in Ang II-exposed cells.
Summary · context
This study assessed senescence markers, including β-galactosidase activity (SA-β-gal) and the senescence-associated secretory phenotype (SASP), in mouse VSMCs treated with Ang II alone or with NMN and relevant activators/inhibitors.
Show in the study text Report a problemFND-4028398801
02LabIn vitro (cells)Mechanism
In mouse VSMCs, NMN reduced the senescence-associated secretory phenotype marker elevated by Ang II.
In plain wordsIn cells from mice, NMN reduced aging-associated secretory markers compared with Ang II alone.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseSASP expression
Study
mousen: not reported in source
Ang II-exposed vascular smooth muscle cells
Comparator
Ang II alone
Outcome group
Aging markers · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
In contrast, NMN reduced the expression of both markers.
2 context sentences(design, population, supporting numbers)
Summary · context
Compared to controls, SA-β-gal levels and SASP secretion significantly increased in Ang II-exposed cells.
Summary · context
This study assessed senescence markers, including β-galactosidase activity (SA-β-gal) and the senescence-associated secretory phenotype (SASP), in mouse VSMCs treated with Ang II alone or with NMN and relevant activators/inhibitors.
Show in the study text Report a problemFND-4028398802
03LabIn vitro (cells)Mechanism
In mouse VSMCs, NMN reversed Ang II-induced senescence.
In plain wordsIn cells from mice, NMN reversed aging changes caused by Ang II.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseVSMC senescence
Study
mousen: not reported in source
Ang II-exposed vascular smooth muscle cells
Comparator
Ang II alone
Outcome group
Aging markers · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
NMN also reversed Ang II-induced VSMCs senescence by downregulating KLF4 and p16 through AMPK activation, which Ang II inhibited, while decreasing mRNA levels of key SASP components.
1 context sentence(design, population, supporting numbers)
Summary · context
This study assessed senescence markers, including β-galactosidase activity (SA-β-gal) and the senescence-associated secretory phenotype (SASP), in mouse VSMCs treated with Ang II alone or with NMN and relevant activators/inhibitors.
Show in the study text Report a problemFND-4028398803
04LabIn vitro (cells)Mechanism
In mouse VSMCs, NMN downregulated KLF4 through AMPK activation.
In plain wordsIn cells from mice, NMN reduced KLF4 through AMPK activation compared with Ang II alone.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseKLF4 expression
Study
mousen: not reported in source
Ang II-exposed vascular smooth muscle cells
Comparator
Ang II alone
Outcome group
Receptor activity and mechanism · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
NMN also reversed Ang II-induced VSMCs senescence by downregulating KLF4 and p16 through AMPK activation, which Ang II inhibited, while decreasing mRNA levels of key SASP components.
1 context sentence(design, population, supporting numbers)
Summary · context
This study assessed senescence markers, including β-galactosidase activity (SA-β-gal) and the senescence-associated secretory phenotype (SASP), in mouse VSMCs treated with Ang II alone or with NMN and relevant activators/inhibitors.
Show in the study text Report a problemFND-4028398804
05LabIn vitro (cells)Mechanism
In mouse VSMCs, NMN downregulated p16 through AMPK activation.
In plain wordsIn cells from mice, NMN reduced p16 through AMPK activation compared with Ang II alone.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
Decreasep16 expression
Study
mousen: not reported in source
Ang II-exposed vascular smooth muscle cells
Comparator
Ang II alone
Outcome group
Aging markers · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
NMN also reversed Ang II-induced VSMCs senescence by downregulating KLF4 and p16 through AMPK activation, which Ang II inhibited, while decreasing mRNA levels of key SASP components.
1 context sentence(design, population, supporting numbers)
Summary · context
This study assessed senescence markers, including β-galactosidase activity (SA-β-gal) and the senescence-associated secretory phenotype (SASP), in mouse VSMCs treated with Ang II alone or with NMN and relevant activators/inhibitors.
Show in the study text Report a problemFND-4028398805
06LabIn vitro (cells)Mechanism
In mouse VSMCs, NMN activated AMPK, which Ang II inhibited.
In plain wordsIn cells from mice, NMN activated AMPK compared with its inhibition by Ang II.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
IncreaseAMPK activation
Study
mousen: not reported in source
Ang II-exposed vascular smooth muscle cells
Comparator
Ang II alone
Outcome group
Receptor activity and mechanism · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
NMN also reversed Ang II-induced VSMCs senescence by downregulating KLF4 and p16 through AMPK activation, which Ang II inhibited, while decreasing mRNA levels of key SASP components.
1 context sentence(design, population, supporting numbers)
Summary · context
This study assessed senescence markers, including β-galactosidase activity (SA-β-gal) and the senescence-associated secretory phenotype (SASP), in mouse VSMCs treated with Ang II alone or with NMN and relevant activators/inhibitors.
Show in the study text Report a problemFND-4028398806
07LabIn vitro (cells)Mechanism
In mouse VSMCs, NMN decreased mRNA levels of key SASP components.
In plain wordsIn cells from mice, NMN reduced genetic messages for aging-associated secretory components compared with Ang II alone.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseSASP component mRNA
Study
mousen: not reported in source
Ang II-exposed vascular smooth muscle cells
Comparator
Ang II alone
Outcome group
Aging markers · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
NMN also reversed Ang II-induced VSMCs senescence by downregulating KLF4 and p16 through AMPK activation, which Ang II inhibited, while decreasing mRNA levels of key SASP components.
1 context sentence(design, population, supporting numbers)
Summary · context
This study assessed senescence markers, including β-galactosidase activity (SA-β-gal) and the senescence-associated secretory phenotype (SASP), in mouse VSMCs treated with Ang II alone or with NMN and relevant activators/inhibitors.
Show in the study text Report a problemFND-4028398807
08LabIn vitro (cells)Mechanism
In mouse VSMCs, AICAR effects were described as similar to NMN effects.
In plain wordsIn cells from mice, AICAR produced effects described as similar to NMN.
Peptide
AICAR (acadesine)
Outcome
Direction not reportedEffects relative to NMN
Study
mousen: not reported in source
Ang II-exposed vascular smooth muscle cells
Comparator
NMN
Outcome group
Aging markers · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
The effects of the AMPK activator AICAR were similar to those of NMN, whereas the AMPK inhibitor Compound C negated NMN's effects.
1 context sentence(design, population, supporting numbers)
Summary · context
This study assessed senescence markers, including β-galactosidase activity (SA-β-gal) and the senescence-associated secretory phenotype (SASP), in mouse VSMCs treated with Ang II alone or with NMN and relevant activators/inhibitors.
Show in the study text Report a problemFND-4028398808

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).

09LabNot a test of NMN (nicotinamide mononucleotide) aloneIn vitro (cells)Mechanism
In mouse VSMCs, the AMPK inhibitor Compound C negated NMN effects.
In plain wordsIn cells from mice, Compound C blocked NMN effects compared with NMN without the inhibitor.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseAMPK inhibition of NMN effects
Study
mousen: not reported in source
Ang II-exposed vascular smooth muscle cells
Comparator
NMN without Compound C
Outcome group
Receptor activity and mechanism · Cardiovascular
Source sentences
Summary
The effects of the AMPK activator AICAR were similar to those of NMN, whereas the AMPK inhibitor Compound C negated NMN's effects.
1 context sentence(design, population, supporting numbers)
Summary · context
This study assessed senescence markers, including β-galactosidase activity (SA-β-gal) and the senescence-associated secretory phenotype (SASP), in mouse VSMCs treated with Ang II alone or with NMN and relevant activators/inhibitors.
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-4028398809

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 3Current
21 Oct 2026, 15:58 UTC
Study results updated
Version 2
21 Oct 2026, 12:50 UTC
Study data updated · source update from Europe PMC
Version 1
21 Oct 2026, 12:50 UTC
First added · source update from Europe PMC

Nicotinamide Mononucleotide (NMN) Improves the Senescence of Mouse Vascular Smooth Muscle Cells Induced by Ang II Through Activating p-AMPK/KLF4 Pathway.

Summary

Results from this study9

Studies that did not test the peptide alone1

Version history

Subjects

Publication types

Keywords