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.
引用
收藏
页数:18
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共 108 条
[21]   The impact of ageing on adipose structure, function and vasculature in the B6D2F1 mouse: evidence of significant multisystem dysfunction [J].
Donato, Anthony J. ;
Henson, Grant D. ;
Hart, Corey R. ;
Layec, Gwenael ;
Trinity, Joel D. ;
Bramwell, R. Colton ;
Enz, Ryley A. ;
Morgan, R. Garrett ;
Reihl, Kelly D. ;
Hazra, Sugata ;
Walker, Ashley E. ;
Richardson, Russell S. ;
Lesniewski, Lisa A. .
JOURNAL OF PHYSIOLOGY-LONDON, 2014, 592 (18) :4083-4096
[22]   A single-cell atlas of human and mouse white adipose tissue [J].
Emont, Margo P. ;
Jacobs, Christopher ;
Essene, Adam L. ;
Pant, Deepti ;
Tenen, Danielle ;
Colleluori, Georgia ;
Di Vincenzo, Angelica ;
Jorgensen, Anja M. ;
Dashti, Hesam ;
Stefek, Adam ;
McGonagle, Elizabeth ;
Strobel, Sophie ;
Laber, Samantha ;
Agrawal, Saaket ;
Westcott, Gregory P. ;
Kar, Amrita ;
Veregge, Molly L. ;
Gulko, Anton ;
Srinivasan, Harini ;
Kramer, Zachary ;
De Filippis, Eleanna ;
Merkel, Erin ;
Ducie, Jennifer ;
Boyd, Christopher G. ;
Gourash, William ;
Courcoulas, Anita ;
Lin, Samuel J. ;
Lee, Bernard T. ;
Morris, Donald ;
Tobias, Adam ;
Khera, Amit, V ;
Claussnitzer, Melina ;
Pers, Tune H. ;
Giordano, Antonio ;
Ashenberg, Orr ;
Regev, Aviv ;
Tsai, Linus T. ;
Rosen, Evan D. .
NATURE, 2022, 603 (7903) :926-+
[23]   Platelet-Derived Growth Factor Receptor Alpha as a Marker of Mesenchymal Stem Cells in Development and Stem Cell Biology [J].
Farahani, Ramin M. ;
Xaymardan, Munira .
STEM CELLS INTERNATIONAL, 2015, 2015
[24]   Identification of Senescent Cells in the Bone Microenvironment [J].
Farr, Joshua N. ;
Fraser, Daniel G. ;
Wang, Haitao ;
Jaehn, Katharina ;
Ogrodnik, Mikolaj B. ;
Weivoda, Megan M. ;
Drake, Matthew T. ;
Tchkonia, Tamara ;
LeBrasseur, Nathan K. ;
Kirkland, James L. ;
Bonewald, Lynda F. ;
Pignolo, Robert J. ;
Monroe, David G. ;
Khosla, Sundeep .
JOURNAL OF BONE AND MINERAL RESEARCH, 2016, 31 (11) :1920-1929
[25]   hypeR: an R package for geneset enrichment workflows [J].
Federico, Anthony ;
Monti, Stefano .
BIOINFORMATICS, 2020, 36 (04) :1307-1308
[26]   Current Understanding on the Role of Lipids in Macrophages and Associated Diseases [J].
Florance, Ida ;
Ramasubbu, Seenivasan .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2023, 24 (01)
[27]   Reduced circulating levels of chemokine CXCL14 in adolescent girls with polycystic ovary syndrome: normalization after insulin sensitization [J].
Garcia-Beltran, Cristina ;
Cereijo, Ruben ;
Quesada-Lopez, Tania ;
Malpique, Rita ;
Lopez-Bermejo, Abel ;
de Zegher, Francis ;
Ibanez, Lourdes ;
Villarroya, Francesc .
BMJ OPEN DIABETES RESEARCH & CARE, 2020, 8 (01)
[28]   The reactome pathway knowledgebase 2022 [J].
Gillespie, Marc ;
Jassal, Bijay ;
Stephan, Ralf ;
Milacic, Marija ;
Rothfels, Karen ;
Senff-Ribeiro, Andrea ;
Griss, Johannes ;
Sevilla, Cristoffer ;
Matthews, Lisa ;
Gong, Chuqiao ;
Deng, Chuan ;
Varusai, Thawfeek ;
Ragueneau, Eliot ;
Haider, Yusra ;
May, Bruce ;
Shamovsky, Veronica ;
Weiser, Joel ;
Brunson, Timothy ;
Sanati, Nasim ;
Beckman, Liam ;
Shao, Xiang ;
Fabregat, Antonio ;
Sidiropoulos, Konstantinos ;
Murillo, Julieth ;
Viteri, Guilherme ;
Cook, Justin ;
Shorser, Solomon ;
Bader, Gary ;
Demir, Emek ;
Sander, Chris ;
Haw, Robin ;
Wu, Guanming ;
Stein, Lincoln ;
Hermjakob, Henning ;
D'Eustachio, Peter .
NUCLEIC ACIDS RESEARCH, 2022, 50 (D1) :D687-D692
[29]   Metabolic Flexibility in Health and Disease [J].
Goodpaster, Bret H. ;
Sparks, Lauren M. .
CELL METABOLISM, 2017, 25 (05) :1027-1036
[30]   GLUCOSE AND FREE FATTY-ACID METABOLISM IN NON-INSULIN-DEPENDENT DIABETES-MELLITUS - EVIDENCE FOR MULTIPLE SITES OF INSULIN RESISTANCE [J].
GROOP, LC ;
BONADONNA, RC ;
DELPRATO, S ;
RATHEISER, K ;
ZYCK, K ;
FERRANNINI, E ;
DEFRONZO, RA .
JOURNAL OF CLINICAL INVESTIGATION, 1989, 84 (01) :205-213