Restoration of NAD+ via inhibition of CD38 improves aging-induced decline in muscle stem cells functions and muscle regeneration

通过抑制 CD38 恢复 NAD 可改善衰老引起的肌肉干细胞功能和肌肉再生的衰退

• 批准号: 22K16408
• 负责人: NAWAZ ALLAH
• 金额: $ 2.91万
• 依托单位: University of Toyama
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Early-Career Scientists
• 财政年份: 2022
• 资助国家: 日本
• 起止时间: 2022-04-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-22K16408/
• 关键词: Muscle Regenration; NAD metabolism; Muscle Stem Cell; Immune cells; Aging

Previous reports show macrophages-derived signals are crucial for regeneration process. Both macrophages and satellite cells require nicotinamide adenine dinucleotide (NAD+) for their biological functions. Aging-related decline in NAD+ is reported to impair regenerative process and significantly inhibits satellite cells differentiation. Administration of NAD+ precursors restore NAD+ deficiency in aged muscle and also enhances recovery process. CD38 is an ectoenzyme to degrade NAD+ and is reportedly increased in inflammatory macrophages during aging. However, how inhibition of CD38 affects satellite cells functions in aging-induced delay in recovery process, remain elusive. We are currently investigating how deletion of CD38 in aged mice affect regenerative capacity of muscle stem cells. Our initial results reveal that blocking/inhibition of CD38 results in restoration of NAD+ and muscle stem cell functions.

以往的研究表明，巨噬细胞来源的信号对再生过程至关重要。巨噬细胞和卫星细胞都需要烟酰胺腺嘌呤二核苷酸（NAD+）来实现其生物学功能。据报道，与衰老相关的NAD+下降会损害再生过程并显著抑制卫星细胞分化。NAD+前体的施用恢复了老化肌肉中的NAD+缺乏，并且还增强了恢复过程。CD 38是一种降解NAD+的胞外酶，据报道在衰老过程中在炎性巨噬细胞中增加。然而，如何抑制CD 38影响卫星细胞功能的老化诱导的延迟恢复过程中，仍然是难以捉摸的。我们目前正在研究老年小鼠中CD 38的缺失如何影响肌肉干细胞的再生能力。我们的初步结果表明，阻断/抑制CD 38导致NAD+和肌肉干细胞功能的恢复。

项目成果

Role of adipose tissue-resident macrophages in the regulation of adipocyte and fibro-adipogenic progenitors.

脂肪组织驻留巨噬细胞在脂肪细胞和纤维脂肪祖细胞的调节中的作用。

• 发表时间: 2022
• 作者: NAWAZ ALLAH;Bilal Muhammad;角朝信;Aslam Muhammad Rahil;五十嵐喜子;西村歩;渡邊善之;桑野剛英;岡部圭介;八木邦公;中川崇;藤坂志帆;戸邉一之.
• 通讯作者: 戸邉一之.

Crosstalk between macrophages and Fibro-adipogenic progenitors in muscle regeneration.

肌肉再生中巨噬细胞和纤维脂肪祖细胞之间的串扰。

• 发表时间: 2022
• 作者: Nawaz A;Kado T;Shiho F;Nakagawa T;Tobe K
• 通讯作者: Tobe K