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The Aging Adipose Organ: Lipid Redistribution, Inflammation, and Cellular Senescence
Published on Jan 1, 2014
· DOI :10.1007/978-1-62703-770-9_5
Michael B. Stout12
Estimated H-index: 12
Tamara Tchkonia37
Estimated H-index: 37
James L. Kirkland6
Estimated H-index: 6
White adipose tissue (WAT) is an immensely plastic organ that plays a vital role in regulating metabolic homeostasis and systemic inflammation. Advancing age mitigates the dynamic nature of WAT which promotes the manifestation of several lipodystrophic-associated comorbidities. Inflammation and the accumulation of senescence cells likely play a key role in this process by inhibiting adipogenesis. The reduction of WAT functional capacity with aging and the role that inflammation and cellular senescence may play in this process will be explored throughout this review.
  • References (125)
  • Cited By (3)
Iordanes Karagiannides23
Estimated H-index: 23
Tamara Tchkonia37
Estimated H-index: 37
+ 6 AuthorsJames L. Kirkland48
Estimated H-index: 48
(Boston University)
Fat mass, adipocyte size and metabolic responsiveness, and preadipocyte differentiation decrease between middle and old age. We show that expression of CCAAT/enhancer binding protein (C/EBP)-α, a key regulator of adipogenesis and fat cell function, declined substantially with aging in differentiating preadipocytes cultured under identical conditions from rats of various ages. Overexpression of C/EBPα in preadipocytes cultured from old rats restored capacity to differentiate into fat cells, indic...
109 Citations Source Cite
James L. Kirkland6
Estimated H-index: 6
(Boston Medical Center),
Charles H. Hollenberg1
Estimated H-index: 1
(Cancer Care Ontario)
The prevalence of obesity is increasing rapidly in Western countries, and associations between obesity and atherosclerosis, diabetes, and other serious diseases are becoming increasingly apparent (Rosenbaum et al. 1997). Frustratingly little progress has been made in developing effective treatments for obesity. Appetite-suppressant drugs, dietary, and behavioral approaches so far result in either loss of only a small percent of fat mass or in transient weight loss with rebound weight gain, often...
7 Citations Source Cite
Published on Feb 1, 1999in The FASEB Journal 5.59
Béatrice Cousin23
Estimated H-index: 23
(Centre national de la recherche scientifique),
Olivier Munoz3
Estimated H-index: 3
(French Institute of Health and Medical Research)
+ 6 AuthorsLuc Pénicaud51
Estimated H-index: 51
(Centre national de la recherche scientifique)
Several lines of evidence have supported a link betweeen adipose tissue and immunocompetent cells. This link is illustrated in obesity, where excess adiposity and impaired immune function have been described in both humans and genetically obese rodents. In addition, numerous factors involved in inflammatory response are secreted by both preadipocytes and macrophages. Here we show that proliferating preadipocytes in cell lines and primary cultures, develop phagocytic activity toward microorganism...
265 Citations Source Cite
Published on Oct 1, 2007in Journal of Immunology 4.54
Dayong Wu34
Estimated H-index: 34
Zhihong Ren12
Estimated H-index: 12
(Centers for Disease Control and Prevention)
+ 4 AuthorsSimin Nikbin Meydani59
Estimated H-index: 59
(Tufts University)
Obesity is a leading risk factor for type 2 diabetes (T2D). Aging is associated with an increase in T2D incidence, which is not totally explained by the much lower prevalence of obesity in the elderly. Low-grade inflammation in adipose tissue (AT) contributes to insulin resistance and T2D. Thus, we determined whether inflammatory responses are up-regulated with age in AT. The results showed that visceral AT from old C57BL mice had significantly higher mRNA expression of the proinflammatory cytok...
165 Citations Source Cite
Published on May 1, 2010in Obesity 4.04
Yuji Yamamoto7
Estimated H-index: 7
(Harvard University),
Stephane Gesta17
Estimated H-index: 17
(Harvard University)
+ 3 AuthorsC. Ronald Kahn127
Estimated H-index: 127
(Harvard University)
We have previously demonstrated that subcutaneous and intra-abdominal adipose tissue show different patterns of expression for developmental genes (Shox2, En1, Tbx15 Hoxa5, Hoxc8, and Hoxc9), and that the expression level of Tbx15 and Hoxa5 in humans correlated with the level of obesity and fat distribution. To further explore the role of these developmental genes in adipose tissue, we have characterized their expression in different adipose depots in mice, and studied their regulation in obesit...
106 Citations Source Cite
Published on May 1, 2010in Obesity 4.04
Katherine Samaras39
Estimated H-index: 39
(Garvan Institute of Medical Research),
Natalia K. Botelho8
Estimated H-index: 8
(University of New South Wales)
+ 1 AuthorsReginald V. Lord36
Estimated H-index: 36
(University of New South Wales)
Type 2 diabetes mellitus (T2D) is predicted by central obesity and circulating adipokines regulating inflammation. We hypothesized that visceral adipose tissue (VAT) in T2D expresses greater levels of proinflammatory molecules. Paired samples of subcutaneous (SAT) and VAT were excised at elective surgery (n = 16, 6 with T2D, n = 8 age- and gender- matched controls). Metabolic parameters were measured in the fasted state: body composition by dual-energy X-ray absorptiometry and insulin action by ...
152 Citations Source Cite
Published on Jun 11, 1999in Journal of Biological Chemistry 4.01
Ron F. Morrison6
Estimated H-index: 6
(Boston University),
Stephen R. Farmer43
Estimated H-index: 43
(Boston University)
Abstract Molecular mechanisms coupling growth arrest and cell differentiation were examined during adipogenesis. Data are presented that document a cascade expression of members of two independent families of cyclin-dependent kinase inhibitors that define distinct states of growth arrest during 3T3-L1 preadipocyte differentiation. Exit from the cell cycle into a pre-differentiation state of post-mitotic growth arrest was characterized by significant increases in p21 and p27. During onset of irre...
261 Citations Source Cite
Published on Oct 1, 2009in Ageing Research Reviews 8.97
Jennifer L. Kuk28
Estimated H-index: 28
(York University),
Travis J. Saunders23
Estimated H-index: 23
(Children's Hospital of Eastern Ontario)
+ 1 AuthorsRobert Ross45
Estimated H-index: 45
(Queen's University)
Aging is associated with progressive changes in total and regional fat distribution that have negative health consequences. Indeed, a preferential increase in abdominal fat, in particular visceral fat, combined with a decrease in lower body subcutaneous fat are commonly cited in the literature. These age-related changes in body composition can occur independent of changes in total adiposity, body weight or waist circumference, and represent a phenotype closely associated with increased morbidity...
291 Citations Source Cite
Published on Feb 1, 1999in Molecular Cell 14.25
Zhidan Wu19
Estimated H-index: 19
(Harvard University),
Evan D. Rosen40
Estimated H-index: 40
(Harvard University)
+ 6 AuthorsBruce M. Spiegelman161
Estimated H-index: 161
(Harvard University)
Abstract Mice deficient in C/EBPα have defective development of adipose tissue, but the precise role of C/EBPα has not been defined. Fibroblasts from C/EBPα(−/−) mice undergo adipose differentiation through expression and activation of PPARγ, though several clear defects are apparent. C/EBPα-deficient adipocytes accumulate less lipid, and they do not induce endogenous PPARγ, indicating that cross-regulation between C/EBPα and PPARγ is important in maintaining the differentiated state. The cells ...
684 Citations Source Cite
Cited By3
Published on Dec 1, 2014in Biogerontology 3.70
Yossi Ovadya10
Estimated H-index: 10
(Weizmann Institute of Science),
Valery Krizhanovsky22
Estimated H-index: 22
(Weizmann Institute of Science)
The progression of physiological ageing is driven by intracellular aberrations including telomere attrition, genomic instability, epigenetic alterations and loss of proteostasis. These in turn damage cells and compromise their functionality. Cellular senescence, a stable irreversible cell-cycle arrest, is elicited in damaged cells and prevents their propagation in the organism. Under normal conditions, senescent cells recruit the immune system which facilitates their removal from tissues. Nevert...
74 Citations Source Cite
Michael B. Stout12
Estimated H-index: 12
(Mayo Clinic),
Frederik J. Steyn17
Estimated H-index: 17
(University of Queensland)
+ 21 AuthorsTamar Pirtskhalava23
Estimated H-index: 23
(Mayo Clinic)
Aging is associated with visceral adiposity, metabolic disorders, and chronic low-grade inflammation. 17α-estradiol (17α-E2), a naturally occurring enantiomer of 17α-estradiol (17α-E2), extends life span in male mice through unresolved mechanisms. We tested whether 17α-E2 could alleviate age-related metabolic dysfunction and inflammation. 17α-E2 reduced body mass, visceral adiposity, and ectopic lipid deposition without decreasing lean mass. These declines were associated with reductions in ener...
23 Citations Source Cite
Asael Roichman2
Estimated H-index: 2
(Bar-Ilan University),
Yariv Kanfi9
Estimated H-index: 9
(Bar-Ilan University)
+ 8 AuthorsJonathan Leor43
Estimated H-index: 43
(Sheba Medical Center)
Abstract The extension in human lifespan in the last century results in a significant increase in incidence of age related diseases. It is therefore crucial to identify key factors that control elderly healthspan. Similar to dietary restriction, mice overexpressing the NAD(+) dependent protein deacylase SIRT6 (MOSES) live longer and have reduced IGF-1 levels. However, it is as yet unknown whether SIRT6 also affects various healthspan parameters. Here, a range of age related phenotypes was evalua...
8 Citations Source Cite
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