Senescent cells promote tissue NAD(+) decline during ageing via the activation of CD38(+) macrophages.
Senescent cells promote tissue NAD(+) decline during ageing via the activation of CD38(+) macrophages.
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DOI：
10.1038/s42255-020-00305-3
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发表时间：
2020-11
影响因子：
20.8
通讯作者：
Verdin E
中科院分区：
文献类型：
--
作者：
Covarrubias AJ;Kale A;Perrone R;Lopez-Dominguez JA;Pisco AO;Kasler HG;Schmidt MS;Heckenbach I;Kwok R;Wiley CD;Wong HS;Gibbs E;Iyer SS;Basisty N;Wu Q;Kim IJ;Silva E;Vitangcol K;Shin KO;Lee YM;Riley R;Ben-Sahra I;Ott M;Schilling B;Scheibye-Knudsen M;Ishihara K;Quake SR;Newman J;Brenner C;Campisi J;Verdin E
组织中烟酰胺腺嘌呤二核苷酸（NAD）水平的下降与衰老及其相关疾病有关。然而，这种下降的机制尚不清楚。在这里，我们表明，促炎性M1样巨噬细胞，但不是幼稚或M2巨噬细胞，积累在代谢组织，包括内脏白色脂肪组织和肝脏，在老化和急性炎症反应。这些M1样巨噬细胞表达高水平的NAD消耗酶CD38，并具有增强的CD38依赖性NAD酶活性，从而降低组织NAD水平。我们还发现衰老细胞在衰老过程中在内脏白色脂肪组织和肝脏中逐渐积累，并且衰老细胞分泌的炎性细胞因子（衰老相关分泌表型，SASP）诱导巨噬细胞增殖并表达CD 38。这些结果揭示了衰老过程中驻留组织巨噬细胞、细胞衰老和组织NAD下降之间的新因果关系，并提供了在衰老过程中维持NAD水平的新治疗机会。
Declining tissue nicotinamide adenine dinucleotide (NAD) levels are linked to ageing and its associated diseases. However, the mechanism for this decline is unclear. Here, we show that pro-inflammatory M1-like macrophages, but not naive or M2 macrophages, accumulate in metabolic tissues, including visceral white adipose tissue and liver, during ageing and acute responses to inflammation. These M1-like macrophages express high levels of the NAD-consuming enzyme CD38 and have enhanced CD38-dependent NADase activity, thereby reducing tissue NAD levels. We also find that senescent cells progressively accumulate in visceral white adipose tissue and liver during ageing and that inflammatory cytokines secreted by senescent cells (the senescence-associated secretory phenotype, SASP) induce macrophages to proliferate and express CD38. These results uncover a new causal link among resident tissue macrophages, cellular senescence and tissue NAD decline during ageing and offer novel therapeutic opportunities to maintain NAD levels during ageing.
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影响因子：
3.7
作者：
Jablonski KA;Amici SA;Webb LM;Ruiz-Rosado Jde D;Popovich PG;Partida-Sanchez S;Guerau-de-Arellano M
通讯作者：
Guerau-de-Arellano M
巨噬细胞的局部扩散有助于与肥胖相关的脂肪组织炎症。
影响因子：
29
作者：
Amano SU;Cohen JL;Vangala P;Tencerova M;Nicoloro SM;Yawe JC;Shen Y;Czech MP;Aouadi M
通讯作者：
Aouadi M
影响因子：
--
作者：
Cho, Kae Won;Morris, David L.;Lumeng, Carey N.
通讯作者：
Lumeng, Carey N.
DOI：
10.1146/annurev-pathol-121808-102144
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
--
作者：
Coppé JP;Desprez PY;Krtolica A;Campisi J
通讯作者：
Campisi J
DOI：
10.1016/j.bbrc.2006.02.109
发表时间：
2006-04-21
影响因子：
3.1
作者：
Iqbal, J;Zaidi, M
通讯作者：
Zaidi, M