老化細胞の治療的除去による若返り

Paul Krimpenfort¹, Anton Berns¹

¹Division of Molecular Genetics, the Netherlands Cancer Institute, Amsterdam, the Netherlands.

Cell

|March 25, 2017

まとめ

FOXO4タンパク質は,p53を隔離することによって,老化細胞におけるアポトーシスを防ぐ. 新しいペプチド (FOXO4- DRI) は,この相互作用を妨害し,p53を復元します.

科学分野:

細胞の老化
アポトーシスの調節
分子相互作用

背景:

細胞老化は逆戻りできない成長停止状態です
衰老する細胞は年齢とともに蓄積され組織機能障害を引き起こします
衰老によるアポトーシスにおけるp53の役割は極めて重要です.

研究の目的:

FOXO4が老化細胞の生存に影響を与えるメカニズムを調査する.
FOXO4- p53の相互作用を妨害することで,老化細胞のアポトーシスを回復できるかどうかを判断する.
この相互作用を年齢に関係した組織変性に対する治療の可能性を評価する.

主な方法:

FOXO4とp53の相互作用を研究するために分子生物学技術を活用した.
FOXO4-p53複合体を破壊するために全Dアミノ酸ペプチド (FOXO4-DRI) を使用した.
衰老細胞の生存能力とアポトーシスの誘導を評価した.
高齢モデルにおける組織ホメオスタシスの評価

主要な成果:

FOXO4は核体内のp53を隔離し,p53媒介によるアポトーシスを阻害する.
FOXO4- DRIペプチドによる治療は,FOXO4- p53の相互作用をうまく破壊しました.
相互作用の障害は,老化細胞におけるp53のアポプトシス機能を回復させた.
FOXO4- DRIは老化に関連した組織ホメオスタシスの減少の影響を改善しました.

結論:

FOXO4は老化細胞の生存維持に保護的な役割を果たします
FOXO4-DRIとFOXO4-p53の相互作用をターゲットにすることは,潜在的な治療戦略を提供します.
p53のアポプトシス機能の回復は,年齢に関連する組織機能障害を逆転させる可能性があります.

さらに関連する動画

08:56

Simultaneous Imaging and Flow-Cytometry-based Detection of Multiple Fluorescent Senescence Markers in Therapy-Induced Senescent Cancer Cells

Published on: July 12, 2022

3.6K

07:39

SA-β-Galactosidase-Based Screening Assay for the Identification of Senotherapeutic Drugs

Published on: June 28, 2019

25.4K

関連する概念動画

02:15

Replicative Cell Senescence

4.5K

Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...

4.5K

01:23

Tissue Renewal without Stem Cells

2.2K

After cellular or tissue damage, the resident stem cells present in the human body can locally repair and regenerate the damaged tissue or organ. However, even though some tissues do not have stem cells, they can repair and regenerate with the help of pre-existing cells. For example, beta cells of the pancreas and hepatocytes of the liver can divide to renew and regenerate the tissue. Here, both cell division and cell death are well regulated by homeostasis.
However, failure of such a system...

2.2K

01:33

Whole Body Regeneration

4.3K

Regeneration is the process of restoring injured or lost tissues, organs, or body parts. While simpler organisms generally show greater ability to regenerate their whole body, few complex animals show similarly exceptional regeneration. For example, planarian flatworms have a unique regenerative potential making them a popular study organism among biologists to understand the mechanisms of whole body regeneration. Other organisms, such as hydra, also show extreme regeneration potential;...

4.3K

01:12

Renewal of Skin Epidermal Stem Cells

3.1K

The skin is divided into epidermis, dermis, and hypodermis, the skin's outermost, middle, and inner layers. The human epidermal layer regularly undergoes renewal, where old, dead cells are replaced by new cells. Epidermal stem cells or EpiSCs divide and differentiate to restore the lost cells. For the renewal process, some EpiSCs continuously self-renew. In contrast, few others differentiate into transit-amplifying cells, which later form prickle or spinous cells, followed by granular...

3.1K

01:21

Stem Cell Therapy for Tissue Regeneration

4.8K

Stem cell therapy is a method used in regenerative medicine to repair and restore function to damaged tissues and organs. Stem cells have the potential to proliferate and differentiate into various tissue types, making them ideal candidates for tissue regeneration. For example, hematopoietic stem cell transplants are commonly used in blood cancer treatment to replenish damaged bone marrow and restore healthy blood cells.
Types of Stem Cells used in Stem Cell Therapy
The two main cell...

4.8K

01:23

Renewal of Intestinal Stem Cells

3.4K

The intestinal epithelial lining rapidly renews every 4 to 5 days. The renewal is facilitated by intestinal stem cells (ISCs) located at the base of the crypt– a gland located at the bottom of each villus. ISCs divide asymmetrically to form new stem cells and progenitor daughter cells. The daughter cells are called transit-amplifying (TA) cells which move upwards along the crypt and either differentiate into absorptive cells– the enterocytes or secretory cells– including the...