Table 2 Link between Sirtuins and IVDD

Guo et al. (1976)

An experimental study

Experimental in vivo and in vitro study

The aim of this report is to validate the expression of Sirt1 in different degrees of IVD degeneration

Sirt1 protein expression level decreased in the discs of high Pfirrmann grade and the score of histological morphology of human intervertebral disc is consistent with the Pfirrmann grade

Sirt1 is a protective mediator in IVD degeneration and the expression of Sirt1 decreases in degenerative disc. Activation of Sirt1 works on suppressing cellular senescence, promoting cell proliferation, and restraining the apoptosis of nucleus pulposus cells

Miyazaki et al. (2015)

An experimental study

In vitro study using human IVD nucleus pulposus (NP) cells

To explore the extent to which SIRT1 affects IVD cells

Recombinant human SIRT1 (rhSIRT1) inhibited the decrease in cell number and induced an increase in autophagic activity. rhSIRT1 decreased the incidence of apoptosis, with a decrease in anti-apoptotic Bcl-2 and an increase in pro-apoptotic Bax, cleaved caspase 3, and cleaved caspase 9 in NP cells under low-nutrient conditions, and these changes were affected by rhSIRT1 inhibition, suggesting that rhSIRT1-induced autophagy has an inhibitory effect on apoptosis

SIRT1 protects against nutrient deprivation-induced mitochondrial apoptosis through autophagy induction in human IVD NP cells

Wang et al. (2013)

An experimental study

in vitro study using human IVD nucleus pulposus (NP) cells

The present study was performed to determine whether degenerative human NP would express SIRT1, and to investigate the role of SIRT1 in NP cells apoptosis

SIRT1 mRNA and protein levels were higher in LVF disc NPs than in DDD disc NPs. the apoptosis rate of resveratrol-treated NP cells was much lower than that of SIRT1 siRNA-transfected or nicotinamide-treated NP cells. After transfection with SIRT1 siRNA, NP cells reduced Akt phosphorylation, whereas resveratrol phosphorylated Akt

SIRT1 plays a critical role in survival of degenerative human NP cells through the Akt anti-apoptotic signaling pathway

Zhang et al. (2019a)

An experimental study

Experimental in vivo and in vitro study

The aim of this study was to investigate the mechanism of action of diabetes mellitus on IDD

The acetylation of p53 was upregulated and the expression and activity of Sirt1 were downregulated in response to glucose in NP cells as well as in diabetic NP tissues. The upregulation of Sirt1 expression and activity reversed the acetylation of p53, which in turn suppressed apoptosis and senescence induced by high glucose in NP cells. Sirt1 plays a protective role against diabetic IDD in a rodent model

Hyperglycaemia may enhance apoptosis and senescence in NP cells both in vivo and in vitro via the Sirt1/acetyl-p53 axis. The activation of Sirt1 may reduce p53 acetylation and potentially protect NP cells against apoptosis and senescence

Wang et al. (2016a)

An experimental study

in vitro study using human IVD nucleus pulposus (NP) cells

The purpose of this study is to investigate whether RSV regulates TNF-α–induced matrix metalloproteinase-3 (MMP-3) expression

Resveratrol (RSV) induced autophagy in human NP cells, and inhibition of autophagy significantly abolished the inhibitory effect of RSV on TNF-α-mediated MMP-3 upregulation. In addition, RSV increased the expression of SIRT1, and knockdown of SIRT1 significantly inhibited RSV-induced autophagy in NP cells.RSV also activated AMP-activated protein kinase (AMPK), and inhibition of AMPK significantly suppressed RSV-induced SIRT1 expression

RSV attenuated TNF-α–induced MMP-3 expression in human NP cells by activating autophagy via AMPK/SIRT1 signaling pathway

Jiang et al. (2014)

An experimental study

in vitro study using human IVD nucleus pulposus (NP) cells

To explore whether autophagy is involved in the protective effect of SIRT1 against apoptosis in NP cells

Resveratrol could increase the protein expression of LC3-II/I and Beclin-1, and reduce apoptosis in degenerative NP cells. In contrast, the protein levels of LC3-II/I and Beclin-1 were down-regulated and apoptosis level was significantly up-regulated in treatment with nicotinamide or SIRT1-siRNA transfection

Autophagy may play an important role in IVD degeneration, and SIRT1 protected degenerative human NP cells against apoptosis via promoting autophagy

He et al. (2021a)

An experimental study

in vitro study using human IVD nucleus pulposus (NP) cells

This study tried to confirm the "early stage" of IVDD and the role of NP cell autophagy during IVDD as well as to determine the mechanism by which SIRT1 protects NP cells

Mildly degenerative (Pfirrmann grade III with normal height of intervertebral disc) NP cells may be the key target for biomolecular interventions in IVDD and that SIRT1 protects human mildly degenerative NP cells from apoptosis by activating autophagy via the ERK signalling pathway

SIRT1 inhibits apoptosis by promoting the autophagic flux in NP cells via the ERK signalling pathway during the key stage of degeneration

Yang et al. (2019)

An experimental study

in vitro study using nucleus pulposus (NP) cells

The aim of this study was to determine whether Sirt2 protected NP from degradation in IDD

The expression of Sirt2 markedly decreased in severe degenerated disc tissues. IL-1β significantly promoted the progress of IDD. Meanwhile, overexpression of Sirt2 could reverse the effects of IL-1β. Sirt2 overexpression obviously increased the production of antioxidant SOD1/2 and suppressed oxidative stress in the disc. Moreover, p53 and p21 could be significantly suppressed by Sirt2 overexpression

Sirt2 prevented NP degradation via restraining oxidative stress and cell senescence through inhibition of the p53/p21 pathway

Hu et al. (2022)

An experimental study

in vitro study using human and rat nucleus pulposus (NP) cells

The aim of this study was to investigate whether HSP70 could regulate the expression of SIRT3

Promoting HSP70 expression protects NP cells from abnormal mechanical loads in vitro and in vivo. HSP70 inhibits compression-induced mitochondrial fission by promoting SIRT3 expression, thereby attenuating mitochondrial dysfunction and reactive oxygen species production, and ultimately inhibiting the mitochondrial apoptotic pathway in NP cells

HSP70 inhibits mitochondrial fission by upregulating SIRT3 expression and attenuates NP cell apoptosis

Mao et al. (2023)

An experimental study

in vitro study using human and rat nucleus pulposus (NP) cells

The aim of this study was to investigate whether desuccinylation modifications of SIRT5 and proteins are involved in the regulation of mitochondrial compression-induced injury in NP cells

Reduced SIRT5 expression resulted in the increased succinylation of AIFM1, which in turn abolished the interaction between AIFM1 and CHCHD4 and thus led to the reduced electron transfer chain (ETC) complex subunits in NP cells. Reduced ETC complex subunits resulted in mitochondrial dysfunction and the subsequent occurrence of IDD under mechanical stress

Excessive mechanical loading increases succinylation levels in NP cells by decreasing the expression of the desuccinylase SIRT5, impairing mitochondrial function and contributing to subsequent IDD development

Chen et al. (2018)

An experimental study

Experimental in vivo and in vitro study

explored whether sirt6 influenced IDD

Sirt6 levels were reduced in senescent human NP cells. sirt6 overexpression prevented apoptosis as well as replication- and stress-induced premature senescence. sirt6 also activated autophagy in NP cells both in vivo and in vitro. the anti-aging and anti-apoptotic effects of sirt6 were partially reversed by 3-methyladenine (3-MA) and chloroquine (CQ)-mediated inhibition of autophagy and sirt6 regulated the expression of denaturation-associated proteins (DAPs), which were also shown to be associated with the development of the NP cells. SIRT6 regulates the expression of degeneration-associated proteins. In vivo, sirt6 overexpression attenuated IDD

sirt6 attenuates cellular senescence by triggering autophagy and reduces apoptosis, ultimately improving IDD