Loss of MTCH-1 suppresses age-related proteostasis collapse through the inhibition of programmed cell death factors

Aman, Yahyah; Erinjeri, Annmary Paul; Tataridas-Pallas, Nikolaos; Williams, Rhianna; Wellman, Rachel; Chapman, Hannah; Labbadia, John

doi:10.1016/j.celrep.2022.111690

Cited by 9 publications

(10 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Under stress conditions, the free HSF1 translocates to the nucleus, leading to the transcription of HSPs, including HSP90 (Pesonen et al., 2021). The activation of HSF1 and the inhibition of HSP90 are considered a possible treatment strategy in neurodegenerative diseases (Aman et al., 2022). Interestingly, in our study, kaempferol treatment of AR‐DOR mice inhibited the phosphorylation activation of HSF1.…”

Section: Discussionmentioning

confidence: 99%

Kaempferol exerts antioxidant effects in age‐related diminished ovarian reserve by regulating the HSP90/NRF2 pathway

Hua,

Zhang,

Han

et al. 2023

Chem Biol Drug Des

View full text Add to dashboard Cite

Kaempferol is the active ingredient of Er‐Xian decoction (EXD), a traditional Chinese medicine formula used clinically to treat ovarian dysfunction, but the mechanism of kaempferol relieving age‐related diminished ovarian reserve (AR‐DOR) is still unclear. In this study, 36 volunteers and 78 DOR patients (37 patients with EXD treatment) were enrolled in the clinical research. Meanwhile, 32‐week‐old female mice were used to establish the AR‐DOR model, and these model mice were intragastrically administered with 100 mg/kg kaempferol in the presence or absence of 200 mg/kg geranylgeranylacetone (GGA) or 1 mg/kg geldanamycin (GDA). The effects of kaempferol on serum hormone levels and oxidative stress‐related indexes were detected by enzyme‐linked immunosorbent assay. Antral follicle count (AFC) was determined by hematoxylin–eosin staining. The protein levels of HSP90 and nuclear factor erythroid 2‐related factor 2 (NRF2) were assayed by Western blot. This study displayed that the serum anti‐Mullerian hormone (AMH) level in DOR patients with EXD treatment was higher than that in DOR patients without EXD treatment. Kaempferol treatment reversed the low levels of AMH, estradiol (E2), AFC, superoxide dismutase (SOD), and catalase (CAT), as well as the high levels of follicle‐stimulating hormone (FSH), reactive oxygen species (ROS), and malonaldehyde (MDA). The results showed that HSP90 was predicted to have high affinity with kaempferol, and its expression was inhibited by kaempferol, while the expression of NRF2, the target of HSP90, was up‐regulated by kaempferol. However, the above effects of kaempferol were reversed by GGA. On the contrary, GDA enhanced the therapeutic effects of kaempferol on AR‐DOR mice. Moreover, the treatment of kaempferol resulted in a reduction in the phosphorylation level of heat shock factor 1 (HSF1), the transcription factor associated with HSP90, and an increase in the phosphorylation level of Src, a client protein of HSP90. In summary, kaempferol exerts an antioxidant effect on AR‐DOR by inhibiting HSP90 expression to up‐regulate NRF2 expression. This study provides a theoretical basis for the clinical application of kaempferol in AR‐DOR.

show abstract

Section: Discussionmentioning

confidence: 99%

Kaempferol exerts antioxidant effects in age‐related diminished ovarian reserve by regulating the HSP90/NRF2 pathway

Hua,

Zhang,

Han

et al. 2023

Chem Biol Drug Des

View full text Add to dashboard Cite

show abstract

“…For instance, suppression of the highly conserved outer mitochondrial membrane protein mitochondrial carrier 1 results in induction of longevity through activation of hsf-1 target genes important for proteostasis such as hsp-16, hsp-70, dnj-19, and cct-1 in C. elegans (Aman et al, 2022).…”

Section: Loss Of Proteostasismentioning

confidence: 99%

“…A possible strategy for proteostasis preservation is the pharmaceutically induction of chaperones to ensure the activation of the chaperon‐mediated autophagy network for toxic protein removal. For instance, suppression of the highly conserved outer mitochondrial membrane protein mitochondrial carrier 1 results in induction of longevity through activation of hsf‐1 target genes important for proteostasis such as hsp‐16 , hsp‐70 , dnj‐19 , and cct‐1 in C. elegans (Aman et al., 2022).…”

Section: “Old” Hallmarks Of Aging—longevity Perspectivementioning

confidence: 99%

Nurturing longevity through natural compounds: Where do we stand, and where do we go?

Todorova,

Savova,

Mihaylova

et al. 2024

Food Frontiers

View full text Add to dashboard Cite

The revolution in aging research through the past decade has driven the progress in interventions that promote longevity. Dissection of the “old” hallmarks of aging has provided solid data for the definition of at least three “new” ones, opening avenues for the development of novel hallmark‐targeted pro‐longevity approaches. The quest for geroprotectors is of enormous interest with the ultimate goal of finding the alchemical stone that induces healthy aging and increases lifespan, pushing the limits of human longevity or even uncovering the absence of such limits. Several of the well‐appreciated geroprotectors that are recognized as longevity promoters are of natural origin such as metformin, resveratrol, aspirin, and spermidine. As the search for pharmacological modulators of healthspan and lifespan continues, numerous studies are focusing on the potential of plant secondary metabolites. The current review attempts to critically assess the available interventions and the breakthrough discoveries in the field of longevity research over the past decade. Correspondingly, novel approaches targeting the hallmarks of aging have been outlined, and the future goals in longevity research have been enlightened. Special emphasis has been placed on the potential of plant‐derived compounds as pro‐longevity agents.

show abstract

“… 4 , 5 , 6 , 7 In response to impaired electron transport chain (ETC) activity or reduced levels of the mitochondrial carrier homologue, MTCH-1/MTCH2, cells can activate mitochondria-to-cytosolic stress responses that converge on the transcription factor HSF-1 to upregulate specific PN components and protect cells against proteostasis collapse later in life. 8 , 9 In addition, increased HSF-1 activity has been shown to extend lifespan through mitochondria associated mechanisms, 10 , 11 suggesting a close relationship between mitochondrial status, HSF-1 activity and proteome integrity. However, it remains unclear whether mitochondria-to-HSF-1 communication plays a role in promoting longevity in response to lifestyle changes that alter mitochondrial function.…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial clearance and increased HSF-1 activity are coupled to promote longevity in fasted Caenorhabditis elegans

Tataridas-Pallas,

Aman,

Williams

et al. 2024

iScience

Self Cite

View full text Add to dashboard Cite

Loss of MTCH-1 suppresses age-related proteostasis collapse through the inhibition of programmed cell death factors

Cited by 9 publications

References 63 publications

Kaempferol exerts antioxidant effects in age‐related diminished ovarian reserve by regulating the HSP90/NRF2 pathway

Kaempferol exerts antioxidant effects in age‐related diminished ovarian reserve by regulating the HSP90/NRF2 pathway

Nurturing longevity through natural compounds: Where do we stand, and where do we go?

Mitochondrial clearance and increased HSF-1 activity are coupled to promote longevity in fasted Caenorhabditis elegans

Contact Info

Product

Resources

About