Facebook PixelPhotoaging – ultraviolet radiation ages the skin
Brainstorming
Tour
Brainstorming
Brainstorming
Create newCreate new
EverythingEverything
ChallengesChallenges
IdeasIdeas
Guide
TourRulesAbout
Challenge

Photoaging – ultraviolet radiation ages the skin

Loading...
LA
Luis Almeida Jan 03, 2021
Please leave the feedback on this challenge
Necessity

Is the problem still unsolved?

Conciseness

Is it concisely described?

Bounty for the best solution

Provide a bounty for the best solution

Bounties attract serious brainpower to the challenge.

Currency *
Bitcoin
Who gets the Bounty *
Distribution
Cellular senescence is a double-edged sword. For one, the accumulation of senescent cells contributes to age-related complications. On the other hand, it is necessary to suppress the uncontrolled proliferation of cells at high-risk of neoplastic transformation, limiting the development of tumors. Senescence is broadly defined as a state of irreversible cell-cycle arrest. Once senescent, cells are unable to proliferate and are less prone to undergo apoptosis. They also tend to secrete several distinct proinflammatory cytokines that disrupt local homeostasis. The myriad of proteins secreted by senescent cells is known as the senescence-associated secretory phenotype (SASP). SASP factors can inhibit cell growth in neighboring cells and recruit leukocytes to maintain an anti-tumorigenic environment and to clear senescent cells.
Besides the natural aging process, certain environmental stresses can induce or accelerate senescence. For example, when the skin is exposed to excessive amounts of ultraviolet (UV) radiation, DNA damage tends to occur. UV radiation can damage DNA directly, or indirectly through the generation of reactive oxygen species. This radiation-induced cellular damage leads to the accumulation of senescent keratinocytes and fibroblasts. Senescent skin cells in the skin are problematic because they have the potential to change the function of nearby cells. Furthermore, senescent cells secrete matrix metalloproteinases, proteins that degrade collagen, an essential skin building block. While the removal of these secreted factors is not trivial, it could represent a method to prevent already established senescent cells from “causing havoc” in the surrounding tissues. Normally, senescence is an anti-tumorigenic process. Paradoxically, UV-induced senescent cells produce proinflammatory cytokines that can actually drive skin cancer; this is known as photoaging. This duality of outcomes has been observed before, with senescent cells promoting both pro-inflammatory (anti-tumorigenic) and anti-inflammatory (pro-tumorigenic) microenvironments, in a context-dependent fashion. The reason why the latter phenotype apparently predominates in UV-induced senescence is not understood. With that in mind, might the following options be able to prevent or delay photoaging? 1 – Could we somehow inhibit the effects of SASP, to prevent established senescent cells from exerting deleterious effects within the surrounding tissue and cells? 2 – Could we promote local immunity to restore a pro-inflammatory environment that allows the immune system to clear senescent cells?
3 – If the former option is scientifically feasible, how could we achieve that without achieving excessive inflammation in an economically viable fashion? 4 – Could the topical application of senolytic creams lead to the creation of a new “anti-skin aging” product? The last option is a particularly exciting novel avenue of treatments, with some very recent promising results. Two senolytic drugs named dasatinib and quercetin were recently shown to decrease p16INK4A- and p21CIP1-positive cells by 38% and 30% in the epidermal layer of the skin, respectively. Because p16INK4A- and p21CIP1 are usually indicators of senescent cells, these drugs could potentially be used for the aforementioned purpose.

[1]Passos JF, Saretzki G, von Zglinicki T. DNA damage in telomeres and mitochondria during cellular senescence: is there a connection? Nucleic acids research. 2007;35(22):7505-13. doi:10.1093/nar/gkm893

[2]Victorelli S, Passos JF. Telomeres and Cell Senescence - Size Matters Not. EBioMedicine. Jul 2017;21:14-20. doi:10.1016/j.ebiom.2017.03.027

[3]Campisi J, d'Adda di Fagagna F. Cellular senescence: when bad things happen to good cells. Nature reviews Molecular cell biology. Sep 2007;8(9):729-40. doi:10.1038/nrm2233

[4]Huda N, Liu G, Hong H, Yan S, Khambu B, Yin XM. Hepatic senescence, the good and the bad. World J Gastroenterol. Sep 14 2019;25(34):5069-5081. doi:10.3748/wjg.v25.i34.5069

[5]Coppé JP, Desprez PY, Krtolica A, Campisi J. The senescence-associated secretory phenotype: the dark side of tumor suppression. Annual review of pathology. 2010;5:99-118. doi:10.1146/annurev-pathol-121808-102144

[6]Schuch AP, Moreno NC, Schuch NJ, Menck CFM, Garcia CCM. Sunlight damage to cellular DNA: Focus on oxidatively generated lesions. Free Radical Biology and Medicine. 2017/06/01/ 2017;107:110-124. doi:https://doi.org/10.1016/j.freeradbiomed.2017.01.029

[7]Campisi J. Aging, cellular senescence, and cancer. Annual review of physiology. 2013;75:685-705. doi:10.1146/annurev-physiol-030212-183653

[8]Bou-Dargham MJ, Khamis ZI, Cognetta AB, Sang QA. The Role of Interleukin-1 in Inflammatory and Malignant Human Skin Diseases and the Rationale for Targeting Interleukin-1 Alpha. Medicinal research reviews. Jan 2017;37(1):180-216. doi:10.1002/med.21406

[9]Eckhart L, Tschachler E, Gruber F. Autophagic Control of Skin Aging. Frontiers in cell and developmental biology. 2019;7:143. doi:10.3389/fcell.2019.00143

[10]Burton DGA, Stolzing A. Cellular senescence: Immunosurveillance and future immunotherapy. Ageing research reviews. May 2018;43:17-25. doi:10.1016/j.arr.2018.02.001

[11]Hickson LJ, Langhi Prata LGP, Bobart SA, et al. Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease. EBioMedicine. Sep 2019;47:446-456. doi:10.1016/j.ebiom.2019.08.069

longevitysenolytics
Creative contributions
Know someone who can contribute to this challenge? Share it with them on , , or

Add your creative contribution

0 / 200

Added via the text editor

Sign up or

or

Guest sign up

* Indicates a required field

By using this platform you agree to our terms of service and privacy policy.

General comments