Topical Rapamycin Evaluated as a Treatment for Skin Aging

This study demonstrates a clear impact of rapamycin treatment on both the molecular signature associated with senescence and the clinical signs of aging in the skin. These data support the idea that a reduction in the burden of senescent cells underlies these improvements. The results could reflect a modification of the senescent cells present in the skin or a reduction in the number of senescent cells. Although rapamycin has been shown to reduce pro-inflammatory secretions produced by senescent cells, the fact that p16INK4A is reduced suggests that the absolute number of senescent cells in the epidermis is reduced. This implies that rather than simply modifying senescent cells present in the tissue, rapamycin treatment is either reducing the number of cells entering senescence or increasing the clearance of senescent cells. Based on our studies demonstrating that rapamycin prevents the senescence transition and improves functionality in vitro, we favor the concept that rapamycin reduces entry into senescence, but we cannot rule out an additional role for clearance of senescent cells. Whether the reduction in senescent cells is due to reduced entry or increased clearance, a reduction in the burden of senescent cells would be expected to improve functionality. Senescent cells produce pro-inflammatory cytokines, matrix metalloproteins, and reduced levels of anti-angiogenic factors, creating a secretory profile known as the Senescence-Associated Secretory Phenotype (SASP)...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs

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Conclusion: Bleeding occurred in 20% of AML at presentation. In patients selected for AS, we found a very low risk of bleeding in sporadic AML justifying our cut off size of 50 mm to trigger intervention. In TSC-associated AML individually tailored follow-up is needed due to a higher intervention rate. PMID: 31971051 [PubMed - as supplied by publisher]
Source: Scandinavian Journal of Urology - Category: Urology & Nephrology Tags: Scand J Urol Source Type: research
Publication date: March 2020Source: Human Pathology: Case Reports, Volume 19Author(s): Charles M. LombardAbstractA 47 yo woman underwent resection of an endometrial adenocarcinoma with pelvic lymph node biopsies. She was found to have incidental nodal lymphangioleiomyomatosis (LAM). Subsequent clinical and radiographic evaluation showed no evidence of manifestations of tuberous sclerosis or pulmonary LAM. Examination of the uterus revealed small microscopic foci of myometrial precursor LAM lesions. These lesions were detected only by immunohistochemical stains for cathepsin K and HMB-45. It is proposed that the precursor c...
Source: Human Pathology: Case Reports - Category: Pathology Source Type: research
AbstractCHD8, which encodes Chromodomain helicase DNA-binding protein 8, is one of a few well-established Autism Spectrum Disorder (ASD) genes. Over 60 mutations have been reported in subjects with variable phenotypes, but little is known concerning genotype –phenotype correlations. We have identified four novel de novo mutations in Chinese subjects: two nonsense variants (c.3562C>T/p.Arg1188X, c.2065C>A/p.Glu689X), a splice site variant (c.4818-1G>A) and a missense variant (c.3502T>A/p.Tyr1168Asn). Three of these were identified from a 445-member ASD cohort by ASD gene panel sequencing of the 96 subjects...
Source: Human Genetics - Category: Genetics & Stem Cells Source Type: research
We present a case of hypovolemic shock due to spontaneous rupture of bilateral giant angiomyolipomas in a 35-year-old female patient with tuberous sclerosis complex (TSC).The hemodynamic instability of the patient leads to an immediate surgery and unilateral nephrectomy was done for the biggest angiomyolipomas. The review of the literature revealed only few cases of spontaneous rupture of renal angiomyolipomas of comparable size.
Source: Urology Case Reports - Category: Urology & Nephrology Source Type: research
ConclusionThe design and implementation of more scalable methods to disseminate research remotely can substantially improve access to clinical trials in rare neurodevelopmental disorders. The lessons learned from this trial can serve as a model for future studies not only in rare conditions, but in other populations that lack adequate access, such as families with limited financial or clinical resources. Continued efforts will further refine delivery methods to enhance efficiency and ease of these delivery systems for families.
Source: Journal of Neurodevelopmental Disorders - Category: Neurology Source Type: research
This review will summarize current knowledge on the burden of illness (BOI) in tuberous sclerosis complex (TSC), a multisystem genetic disorder manifesting with hamartomas throughout the body, including mainly...
Source: Orphanet Journal of Rare Diseases - Category: Internal Medicine Authors: Tags: Review Source Type: research
Loss of the tumor suppressor tuberous sclerosis complex 1 (Tsc1) in the liver promotes gluconeogenesis and glucose intolerance. We asked whether this could be attributed to aberrant expression of small RNAs. We performed small-RNA sequencing on liver of Tsc1-knockout mice, and found that miRNAs of the delta-like homolog 1 (Dlk1)–deiodinase...
Source: Proceedings of the National Academy of Sciences - Category: Science Authors: Tags: Biological Sciences Source Type: research
Authors: Rhizlane A, Jaafar D, Bourakba S, Siham C, Maadan A, Sekhsoukh R PMID: 31952877 [PubMed - as supplied by publisher]
Source: Journal Francais d Ophtalmologie - Category: Opthalmology Tags: J Fr Ophtalmol Source Type: research
AbstractTuberous sclerosis complex (TSC) is an autosomal dominant disease characterized by the benign tumor formation in multiple organs. The main etiology of TSC is the loss ‐of‐function mutation ofTSC1 orTSC2 gene, which leads to aberrant activation of mammalian target of rapamycin complex 1 (mTORC1). In this research, we found a significant increase of 6 ‐phosphofructo‐2‐kinase/fructose‐2,6‐biphosphatase 3 (PFKFB3) expression in Tsc1−/− and Tsc2−/− mouse embryonic fibroblasts (MEFs) compared with the control cells. Inhibition of mTORC1 led to a dramatic decrease of PFKFB3 expression...
Source: IUBMB Life - Category: Research Authors: Tags: RESEARCH COMMUNICATION Source Type: research
Abstract Renal angiomyolipoma (AML) is the most common benign tumor of the kidney. It consists of blood vessels, smooth muscle and fat components in varying proportions. AML is divided into the sporadic type and tuberous sclerosis complex (TSC)-associated type. TSC-associated AML develops at a younger age and tends to exhibit a much faster growth rate over time than sporadic AML. AMLs are classified as classic AML, fat-poor AML and epithelioid AML. Epithelioid AML, though rare, shows aggressive behavior leading to distant metastasis and mortality. TSC-associated AML is more likely to have an epithelioid component ...
Source: Asian Journal of Surgery - Category: Surgery Authors: Tags: Asian J Surg Source Type: research
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