Related Experiment Video

Updated: Mar 16, 2026

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α
11:27

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α

Published on: November 2, 2018

9.6K

The underlying mechanism of proinflammatory NF-κB activation by the mTORC2/Akt/IKKα pathway during skin aging

Yeon Ja Choi1, Kyoung Mi Moon1, Ki Wung Chung1

  • 1Molecular Inflammation Research Center for Aging Intervention, College of Pharmacy, Pusan National University, Busan, Korea.

Oncotarget
|August 4, 2016
PubMed

Insights

The mammalian target of rapamycin complex 2 (mTORC2) pathway is upregulated in both intrinsic and photo-induced skin aging. Inhibiting mTORC2 may offer therapeutic potential for mitigating skin aging and photoaging.

Area of Science:

  • Cellular and Molecular Biology
  • Dermatology
  • Aging Research

Background:

  • The mammalian target of rapamycin (mTOR) pathway is a known mediator of aging.
  • The specific role of mTOR complex 2 (mTORC2) in skin aging, influenced by intrinsic and extrinsic factors like UV irradiation, remains largely undetermined.
  • Understanding mTORC2's function in skin aging is crucial for developing targeted anti-aging strategies.

Purpose of the Study:

  • To investigate the role and activity of the mTORC2 pathway in intrinsic and photo-induced skin aging.
  • To elucidate the molecular mechanisms linking mTORC2 signaling to skin aging, particularly its interaction with nuclear factor-κB (NF-κB).
  • To assess the therapeutic potential of targeting mTORC2 for ameliorating skin aging.

Main Methods:

  • Analysis of mTORC2 activity and its component rictor in aged and UVB-irradiated mouse skin.
  • In vivo and in vitro studies using HaCaT human keratinocytes to confirm UVB-induced signaling pathways.
  • Pharmacological inhibition and genetic knockdown (RICTOR) of mTORC2 to evaluate its effect on NF-κB activation.

Main Results:

  • mTORC2 activity and rictor expression were significantly upregulated in both intrinsic and photo-induced skin aging models.
  • UVB irradiation and aging led to increased Akt activation and phosphorylation of IκB kinase α (IKKα) at Thr23, mediated by mTORC2.
  • Activation of the mTORC2/Akt/IKKα pathway was directly linked to NF-κB activation in aged and photo-damaged skin.
  • Suppression of mTORC2 activity partially rescued UVB-induced NF-κB activation, highlighting its role in the aging process.

Conclusions:

  • The mTORC2 pathway is upregulated in intrinsic and photo-induced skin aging, contributing to IKKα/NF-κB activation.
  • These findings expand the known functions of mTOR signaling into the realm of skin aging.
  • Targeting mTORC2 presents a promising therapeutic strategy for combating both intrinsic skin aging and photoaging.
Keywords:
GerotargetNF-κBUVmTORC2skin aging

More Related Videos

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway07:15

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway

Published on: August 23, 2024

1.0K
Human Ex vivo Wound Model and Whole-Mount Staining Approach to Accurately Evaluate Skin Repair07:32

Human Ex vivo Wound Model and Whole-Mount Staining Approach to Accurately Evaluate Skin Repair

Published on: February 17, 2021

9.0K

Related Concept Videos

NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
10.2K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
6.1K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
5.0K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

1.6K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
9.0K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
13.7K