Journal of Investigative Dermatology

2022

DOI: 10.1016/j.jid.2022.04.028

|View full text |Cite

|

Sign up to set email alerts

|

Skin Aging in Long-Lived Naked Mole-Rats Is Accompanied by Increased Expression of Longevity-Associated and Tumor Suppressor Genes

¹

,

²

,

Natalia V. Botchkareva

³

et al.

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...

Discussion2

Loss-of-function Mutations In Skin Collagen Genes Lead To An...1

The Longevity Bottleneck Hypothesis1

Introduction To the Skin Immune System And Its Functions1

Citation Types

Supporting

0

Mentioning

8

Contrasting

0

Year Published

2022

2022

2024

2024

Publication Types

Select...

Article5

Preprint2

Relationship

Self Cite1

Independent6

Authors

Journals

Cited by 10 publications

(9 citation statements)

References 98 publications

Supporting

0

Mentioning

8

Contrasting

0

Order By: Relevance

“…[ 38 ] Although the relationship between Cdkn2c and psoriasis has not been elucidated, it has been reported that Cdkn2c levels are increased in the skin of aged Naked mole‐rats. [ 39 ] Using the psoriasis animal model and cell model, we found Cdkn2c was downregulated, and further decreased Cdkn2c expression after HFD exposure. This suggested that the abnormal epidermal proliferation induced by obesity may be related to Cdkn2c regulated keratinocytes proliferation.…”

Section: Discussionmentioning

confidence: 99%

Bcat2‐Mediated Branched‐Chain Amino Acid Catabolism Is Linked to the Aggravated Inflammation in Obese with Psoriasis Mice

Wang,

Zhao,

Meng

et al. 2024

Molecular Nutrition Food Res

View full text Add to dashboard Cite

Scope: The global prevalence of obesity has significantly increased, presenting a major health challenge. High‐fat diet (HFD)‐induced obesity is closely related to the disease severity of psoriasis, but the mechanism is not fully understood.Methods and results: The study utilizes the HFD‐induced obesity model along with an imiquimod (IMQ)‐induced psoriasis‐like mouse model (HFD‐IMQ) to conduct transcriptomics and metabolomic analyses. HFD‐induced obese mice exhibits more severe psoriasis‐like lesions compared to normal diet (ND)‐IMQ mice. The expression of genes of the IL‐17 signaling pathway (IL‐17A, IL‐17F, S100A9, CCL20, CXCL1) is significantly upregulated, leading to an accumulation of T cells and neutrophils in the skin. Moreover, the study finds that there is an inhibition of the branched‐chain amino acids (BCAAs) catabolism pathway, and the key gene branched‐chain amino transferase 2 (Bcat2) is significantly downregulated, and the levels of leucine, isoleucine, and valine are elevated in the HFD‐IMQ mice. Furthermore, the study finds that the peroxisome proliferator‐activated receptor gamma (PPAR γ) is inhibited, while STAT3 activity is promoted in HFD‐IMQ mice.Conclusion: HFD‐induced obesity significantly amplifies IL‐17 signaling and exacerbates psoriasis, with a potential role played by Bcat2‐mediated BCAAs metabolism. The study suggests that BCAA catabolism and PPAR γ‐STAT3 exacerbate inflammation in psoriasis with obesity.

“…[ 38 ] Although the relationship between Cdkn2c and psoriasis has not been elucidated, it has been reported that Cdkn2c levels are increased in the skin of aged Naked mole‐rats. [ 39 ] Using the psoriasis animal model and cell model, we found Cdkn2c was downregulated, and further decreased Cdkn2c expression after HFD exposure. This suggested that the abnormal epidermal proliferation induced by obesity may be related to Cdkn2c regulated keratinocytes proliferation.…”

Section: Discussionmentioning

confidence: 99%

Bcat2‐Mediated Branched‐Chain Amino Acid Catabolism Is Linked to the Aggravated Inflammation in Obese with Psoriasis Mice

Wang,

Zhao,

Meng

et al. 2024

Molecular Nutrition Food Res

View full text Add to dashboard Cite

Scope: The global prevalence of obesity has significantly increased, presenting a major health challenge. High‐fat diet (HFD)‐induced obesity is closely related to the disease severity of psoriasis, but the mechanism is not fully understood.Methods and results: The study utilizes the HFD‐induced obesity model along with an imiquimod (IMQ)‐induced psoriasis‐like mouse model (HFD‐IMQ) to conduct transcriptomics and metabolomic analyses. HFD‐induced obese mice exhibits more severe psoriasis‐like lesions compared to normal diet (ND)‐IMQ mice. The expression of genes of the IL‐17 signaling pathway (IL‐17A, IL‐17F, S100A9, CCL20, CXCL1) is significantly upregulated, leading to an accumulation of T cells and neutrophils in the skin. Moreover, the study finds that there is an inhibition of the branched‐chain amino acids (BCAAs) catabolism pathway, and the key gene branched‐chain amino transferase 2 (Bcat2) is significantly downregulated, and the levels of leucine, isoleucine, and valine are elevated in the HFD‐IMQ mice. Furthermore, the study finds that the peroxisome proliferator‐activated receptor gamma (PPAR γ) is inhibited, while STAT3 activity is promoted in HFD‐IMQ mice.Conclusion: HFD‐induced obesity significantly amplifies IL‐17 signaling and exacerbates psoriasis, with a potential role played by Bcat2‐mediated BCAAs metabolism. The study suggests that BCAA catabolism and PPAR γ‐STAT3 exacerbate inflammation in psoriasis with obesity.

“…Our data demonstrated that m6A modi cation and SOCS3 are involved senescence of SkMSCs, suggesting that intervention of m6A modi cation and m6A might be a potential strategy for regulating cell senescence. SOCS3 function as a negative regulator of the JAK-STAT pathway, which plays a crucial role in agerelated diseases and cellular aging 37,38 . The role of SOCS3 in aging regulation is achieved by inhibiting JAK-STAT pathway, and other related mediators.…”

Section: Discussionmentioning

confidence: 99%

N6-methyladenosine-mediated changes in SOCS3 expression regulate skeletal muscle stem cell senescence

¹

,

²

,

³

et al. 2022

Preprint

View full text Add to dashboard Cite

N6-methyladenosine (m6A)-associated mechanisms are involved in cellular metabolic activities; however, their role in skeletal muscle stem cell (SkMSC) senescence is unknown. In this study, m6A RNA modification and METTL3 expression were decreased in aged SkMSCs from mice. Transcriptional analysis of m6A modification further revealed that suppressor of cytokine signaling 3 (SOCS3) was downregulated in aged SkMSCs, and that downregulation of METTL3 promoted SkMSC senescence. In addition, the upregulation of METTL3 alleviated the senescence of SkMSCs. Mechanistically, deletion of m6A modifications promoted senescence and inhibited SOCS3 expression, whereas downregulation of SOCS3 promoted senescence. Moreover, insulin-like growth factor-2 mRNA-binding protein 1 (IGF2BP1) was identified as an important regulator in the recognition and stabilization of m6A modified SOCS3 expression. IGF2BP1 binds to SOCS3 and reinforces its stability by suppressing the phosphorylation of JAK2/STAT3. Therefore, METTL3 inhibits SkMSC senescence through m6A modification-dependent stabilization of SOCS3 expression and inhibition of JAK2-STAT3 signaling. This study thus highlights a novel mechanism underlying SkMSC senescence.

“…A prime candidate for such a role is the age-related decline in skin collagen gene expression (Fig. S4A) 69 , a phenomenon well-documented in various organisms, including rodents and humans [70][71][72][73] .…”

Section: Loss-of-function Mutations In Skin Collagen Genes Lead To An...mentioning

confidence: 99%

Skin Collagen Reduction Drives Selective Aspects of Aging in Sensory Neurons

Krishna,

Franitza,

E

2024

Preprint

View full text Add to dashboard Cite

Despite significant progress in understanding the molecular processes of aging-associated neurodegeneration, the upstream mechanisms driving neuronal aging remain elusive. Here, we investigate the potential regulatory roles of non-neural tissues in neuronal aging, using Caenorhabditis elegans PVD polymodal neuron as a model. We find that cutaneous PVD neurons develop progressive excessive dendritic branching during normal aging, functionally correlated with age-related deficits in proprioception. Our study reveals that age-related reduction in skin collagens, a common change across species, triggers the aging process of PVD. Specifically, loss-of-function mutations or adulthood-specific RNAi knockdown of skin collagen genes,dpy-5orcol-120, which are downregulated with age, induce an early onset of PVD excessive dendritic branching and proprioception deficits. Overexpressingdpy-5orcol-120mitigates the development of excessive branching without affecting lifespan, suggesting a skin collagens′ role in promoting healthspan rather than longevity. Notably, neitherdpy-5orcol-120is not involved in aging-associated dendritic beading, another degenerative phenotype in PVD associated with harsh touch response deficits. Moreover,dpy-5mutation induces ectopic branching in ALM, but does not affect PLM, two other cutaneous sensory neurons. Finally, we identifyrig-3, a neuronal Immunoglobulin Superfamily member not expressed in PVD or the skin, functioning in the same pathway as skin collagen genes to preserve PVD neuron integrity during aging. Our findings reveal the causative role of age-related reduction in skin collagens in neuronal aging, selectively impacting distinct neuron subtypes and structures. This study underscores the importance of exploring multi-tissue strategies to comprehensively address the complexities of neuronal aging.

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

hi@scite.ai

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

Product

Browser Extension Assistant by scite Citation Statement Search Reference Check Visualizations Dashboards Explore Journals Explore Organizations Explore Funders Embedding Badge Embedding Citation Search Pricing

Resources

Blog Help & FAQ Accessibility Statement API Terms For Universities & Governments For Researchers For Publishers For Corporate, Pharma & Enterprise Author Marketing Become an Affiliate Get an organization trial or quote scite Data & Services

About

News & Press Careers Read our Paper Coverage

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Copyright © 2024 scite LLC. All rights reserved.

Made with 💙 for researchers

Part of the Research Solutions Family.