Age-Related Changes in the Content of Sirtuin 1 in Human Dermal Fibroblasts

2017 ◽  
Vol 7 (4) ◽  
pp. 302-306 ◽  
Author(s):  
N. N. Golubtsova ◽  
F. N. Filippov ◽  
A. G. Gunin
Keyword(s):  
Dermal Fibroblasts ◽  
Sirtuin 1 ◽  
Human Dermal Fibroblasts ◽  
Age Related ◽  
Age Related Changes

Stromal Changes In The Aged Lung Induce An Emergence From Melanoma Dormancy

2020 ◽  
Author(s):  
Ashani Weeraratna ◽  
Mitchell Fane ◽  
Stephen Douglass ◽  
Gretchen Alicea ◽  
Marie Webster ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Residual Disease ◽  
Melanoma Cells ◽  
Dermal Fibroblasts ◽  
Lung Fibroblasts ◽  
Age Related ◽  
Aged Skin ◽  
Phenotype Switching ◽  
Induced Changes ◽  
Age Related Changes

Abstract Dormant tumor cells escape the primary site, do not grow out into macroscopic tumors in the distal site, but maintain enough plasticity to reactivate and form overt metastatic lesions, sometimes taking several decades. Despite its importance in metastasis and residual disease, few studies have been able to successfully model or characterize dormancy within melanoma. Here, we show that age-related changes in the lung microenvironment facilitate a permissive niche for efficient outgrowth of disseminated dormant tumor cells, in contrast to the aged skin, where age-related changes suppress melanoma growth but drive dissemination. A model of melanoma progression that addresses these microenvironmental complexities is the phenotype switching model, which argues that melanoma cells switch between a proliferative cell state and a slower-cycling, invasive state1–3. Dermal fibroblasts are key orchestrators of promoting phenotype switching in melanoma via changes in the secretion of soluble factors during aging4–8. Specifically, we have identified Wnt5A as a master regulator of activating metastatic dormancy, which enables efficient seeding and survival of melanoma cells in metastatic niches. Age-induced reprogramming of lung fibroblasts increases their secretion of the soluble Wnt antagonist sFRP1, which inhibits Wnt5A, enabling efficient metastatic outgrowth. Further, we have identified the tyrosine kinase receptors AXL and MER as promoting a dormancy-to-reactivation axis respectively. Overall, we find that age-induced changes in distal metastatic microenvironments promotes efficient reactivation of dormant melanoma cells in the lung.

The Influence of Metformin on Age-Related Changes in the Number and Proliferation of Dermal Fibroblasts in Mice

2019 ◽  
Vol 9 (1) ◽  
pp. 81-85
Author(s):  
A. G. Gunin ◽  
N. N. Golubtsova ◽  
N. O. Subbotkina ◽  
A. S. Subbotkin
Keyword(s):  
Dermal Fibroblasts ◽  
Age Related ◽  
Age Related Changes

scholarly journals Age-related changes in female scalp dermal sheath and dermal fibroblasts: how the hair follicle environment impacts hair ageing

2020 ◽  
Author(s):  
Rachael Williams ◽  
Gillian E. Westgate ◽  
Alison D. Pawlus ◽  
Stephen k Sikkink ◽  
M Julie Thornton
Keyword(s):  
Hair Follicle ◽  
Dermal Fibroblasts ◽  
Age Related ◽  
Age Related Changes

scholarly journals Inhibition of 3-phosphoinositide–dependent protein kinase 1 (PDK1) can revert cellular senescence in human dermal fibroblasts

2020 ◽  
Vol 117 (49) ◽  
pp. 31535-31546
Author(s):  
Sugyun An ◽  
Si-Young Cho ◽  
Junsoo Kang ◽  
Soobeom Lee ◽  
Hyung-Su Kim ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Protein Kinase ◽  
Cellular Senescence ◽  
Nuclear Factor Κb ◽  
Dermal Fibroblasts ◽  
Quiescent State ◽  
Human Dermal Fibroblasts ◽  
Dependent Protein Kinase ◽  
Age Related ◽  
Dependent Protein

Cellular senescence is defined as a stable, persistent arrest of cell proliferation. Here, we examine whether senescent cells can lose senescence hallmarks and reenter a reversible state of cell-cycle arrest (quiescence). We constructed a molecular regulatory network of cellular senescence based on previous experimental evidence. To infer the regulatory logic of the network, we performed phosphoprotein array experiments with normal human dermal fibroblasts and used the data to optimize the regulatory relationships between molecules with an evolutionary algorithm. From ensemble analysis of network models, we identified 3-phosphoinositide–dependent protein kinase 1 (PDK1) as a promising target for inhibitors to convert the senescent state to the quiescent state. We showed that inhibition of PDK1 in senescent human dermal fibroblasts eradicates senescence hallmarks and restores entry into the cell cycle by suppressing both nuclear factor κB and mTOR signaling, resulting in restored skin regeneration capacity. Our findings provide insight into a potential therapeutic strategy to treat age-related diseases associated with the accumulation of senescent cells.

scholarly journals The Role of microRNAs in Organismal and Skin Aging

2020 ◽  
Vol 21 (15) ◽  
pp. 5281
Author(s):  
Marta Gerasymchuk ◽  
Viktoriia Cherkasova ◽  
Olga Kovalchuk ◽  
Igor Kovalchuk
Keyword(s):  
Replicative Senescence ◽  
Skin Aging ◽  
Dermal Fibroblasts ◽  
Telomere Maintenance ◽  
Sirtuin 1 ◽  
Aging Effects ◽  
Inhibition Of Proliferation ◽  
Biomarkers Of Aging ◽  
Age Related

The aging process starts directly after birth and lasts for the entire lifespan; it manifests itself with a decline in an organism’s ability to adapt and is linked to the development of age-related diseases that eventually lead to premature death. This review aims to explore how microRNAs (miRNAs) are involved in skin functioning and aging. Recent evidence has suggested that miRNAs regulate all aspects of cutaneous biogenesis, functionality, and aging. It has been noted that some miRNAs were down-regulated in long-lived individuals, such as let-7, miR-17, and miR-34 (known as longevity-related miRNAs). They are conserved in humans and presumably promote lifespan prolongation; conversely, they are up-regulated in age-related diseases, like cancers. The analysis of the age-associated cutaneous miRNAs revealed the increased expression of miR-130, miR-138, and miR-181a/b in keratinocytes during replicative senescence. These miRNAs affected cell proliferation pathways via targeting the p63 and Sirtuin 1 mRNAs. Notably, miR-181a was also implicated in skin immunosenescence, represented by the Langerhans cells. Dermal fibroblasts also expressed increased the levels of the biomarkers of aging that affect telomere maintenance and all phases of the cellular life cycle, such as let-7, miR-23a-3p, 34a-5p, miR-125a, miR-181a-5p, and miR-221/222-3p. Among them, the miR-34 family, stimulated by ultraviolet B irradiation, deteriorates collagen in the extracellular matrix due to the activation of the matrix metalloproteinases and thereby potentiates wrinkle formation. In addition to the pro-aging effects of miRNAs, the plausible antiaging activity of miR-146a that antagonized the UVA-induced inhibition of proliferation and suppressed aging-related genes (e.g., p21WAF-1, p16, and p53) through targeting Smad4 has also been noticed. Nevertheless, the role of miRNAs in skin aging is still not fully elucidated and needs to be further discovered and explained.

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