Aging human abdominal subcutaneous white adipose tissue at single cell resolution

被引:6
作者
Whytock, K. L. [1 ]
Divoux, A. [1 ]
Sun, Y. [2 ]
Pino, M. F. [1 ]
Yu, G. [1 ]
Jin, C. A. [3 ]
Robino, J. J. [4 ]
Plekhanov, A. [4 ]
Varlamov, O. [4 ]
Smith, S. R. [1 ]
Walsh, M. J. [2 ]
Sparks, L. M. [1 ]
机构
[1] AdventHealth, Translat Res Inst, Orlando, FL 32803 USA
[2] Icahn Sch Med Mt Sinai, New York, NY USA
[3] Stanford Univ, Sch Med, Dept Genet, Stanford, CA USA
[4] Oregon Natl Primate Res Ctr, Div Metab Hlth & Dis, Beaverton, OR USA
关键词
aging; senescence; single nuclei RNA-Seq; White adipose tissue; SENESCENT SECRETORY PHENOTYPE; MAST-CELLS; INSULIN-RESISTANCE; FAT; FIBROSIS; INFLAMMATION; AGE; OBESITY; HEALTH; MACROPHAGES;
D O I
10.1111/acel.14287
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
White adipose tissue (WAT) is a robust energy storage and endocrine organ critical for maintaining metabolic health as we age. Our aim was to identify cell-specific transcriptional aberrations that occur in WAT with aging. We leveraged full-length snRNA-Seq and histology to characterize the cellular landscape of human abdominal subcutaneous WAT in a prospective cohort of 10 younger (<= 30 years) and 10 older individuals (>= 65 years) balanced for sex and body mass index (BMI). The older group had greater cholesterol, very-low-density lipoprotein, triglycerides, thyroid stimulating hormone, and aspartate transaminase compared to the younger group (p < 0.05). We highlight that aging WAT is associated with adipocyte hypertrophy, increased proportions of lipid-associated macrophages and mast cells, an upregulation of immune responses linked to fibrosis in pre-adipocyte, adipocyte, and vascular populations, and highlight CXCL14 as a biomarker of these processes. We show that older WAT has elevated levels of senescence marker p16 in adipocytes and identify the adipocyte subpopulation driving this senescence profile. We confirm that these transcriptional and phenotypical changes occur without overt fibrosis and in older individuals that have comparable WAT insulin sensitivity to the younger individuals.
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页数:18
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共 108 条
[1]   Single cell transcriptomics suggest that human adipocyte progenitor cells constitute a homogeneous cell population [J].
Acosta, Juan R. ;
Joost, Simon ;
Karlsson, Kasper ;
Ehrlund, Anna ;
Li, Xidan ;
Aouadi, Myriam ;
Kasper, Maria ;
Arner, Peter ;
Ryden, Mikael ;
Laurencikiene, Jurga .
STEM CELL RESEARCH & THERAPY, 2017, 8
[2]   STACAS: Sub-Type Anchor Correction for Alignment in Seurat to integrate single-cell RNA-seq data [J].
Andreatta, Massimo ;
Carmona, Santiago J. .
BIOINFORMATICS, 2021, 37 (06) :882-884
[3]   Defining the lineage of thermogenic perivascular adipose tissue [J].
Angueira, Anthony R. ;
Sakers, Alexander P. ;
Holman, Corey D. ;
Cheng, Lan ;
Arbocco, Michelangella N. ;
Shamsi, Farnaz ;
Lynes, Matthew D. ;
Shrestha, Rojesh ;
Okada, Chihiro ;
Batmanov, Kirill ;
Susztak, Katalin ;
Tseng, Yu-Hua ;
Liaw, Lucy ;
Seale, Patrick .
NATURE METABOLISM, 2021, 3 (04) :469-+
[4]   Calorie restriction reduces biomarkers of cellular senescence in humans [J].
Aversa, Zaira ;
White, Thomas A. ;
Heeren, Amanda A. ;
Hulshizer, Cassondra A. ;
Saul, Dominik ;
Zhang, Xu ;
Molina, Anthony J. A. ;
Redman, Leanne M. ;
Martin, Corby K. ;
Racette, Susan B. ;
Huffman, Kim M. ;
Bhapkar, Manjushri ;
Khosla, Sundeep ;
Das, Sai Krupa ;
Fielding, Roger A. ;
Atkinson, Elizabeth J. ;
Lebrasseur, Nathan K. .
AGING CELL, 2024, 23 (02)
[5]   Spatial mapping reveals human adipocyte subpopulations with distinct sensitivities to insulin [J].
Baeckdahl, Jesper ;
Franzen, Lovisa ;
Massier, Lucas ;
Li, Qian ;
Jalkanen, Jutta ;
Gao, Hui ;
Andersson, Alma ;
Bhalla, Nayanika ;
Thorell, Anders ;
Ryden, Mikael ;
Stahl, Patrik L. ;
Mejhert, Niklas .
CELL METABOLISM, 2021, 33 (09) :1869-+
[6]   Ectopic lipid storage and insulin resistance: a harmful relationship [J].
Boren, J. ;
Taskinen, M. -R. ;
Olofsson, S. -O. ;
Levin, M. .
JOURNAL OF INTERNAL MEDICINE, 2013, 274 (01) :25-40
[7]   Cellular senescence: when bad things happen to good cells [J].
Campisi, Judith ;
di Fagagna, Fabrizio d'Adda .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2007, 8 (09) :729-740
[8]   Peripheral fat loss and decline in adipogenesis in older humans [J].
Caso, Giuseppe ;
McNurlan, Margaret A. ;
Mileva, Izolda ;
Zemlyak, Alla ;
Mynarcik, Dennis C. ;
Gelato, Marie C. .
METABOLISM-CLINICAL AND EXPERIMENTAL, 2013, 62 (03) :337-340
[9]   The chemokine CXCL14 is negatively associated with obesity and concomitant type-2 diabetes in humans [J].
Cereijo, Ruben ;
Quesada-Lopez, Tania ;
Gavalda-Navarro, Aleix ;
Tarasco, Jordi ;
Pellitero, Silvia ;
Reyes, Marjorie ;
Puig-Domingo, Manel ;
Giralt, Marta ;
Sanchez-Infantes, David ;
Villarroya, Francesc .
INTERNATIONAL JOURNAL OF OBESITY, 2021, 45 (03) :706-710
[10]   CXCL14, a Brown Adipokine that Mediates Brown-Fat-to-Macrophage Communication in Thermogenic Adaptation [J].
Cereijo, Ruben ;
Gavalda-Navarro, Aleix ;
Cairo, Montserrat ;
Quesada-Lopez, Tania ;
Villarroya, Joan ;
Moron-Ros, Samantha ;
Sanchez-Infantes, David ;
Peyrou, Marion ;
Iglesias, Roser ;
Mampel, Teresa ;
Turatsinze, Jean-Valery ;
Eizirik, Decio L. ;
Giralt, Marta ;
Villarroya, Francesc .
CELL METABOLISM, 2018, 28 (05) :750-+