Adipose tissue aging: pathophysiological and clinical aspects

G. V. Semikova; Yu. Sh. Khalimov; A. R. Volkova

doi:10.14341/omet13069

Adipose tissue aging: pathophysiological and clinical aspects

G. V. Semikova, Yu. Sh. Khalimov, A. R. Volkova

https://doi.org/10.14341/omet13069

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Abstract

Adipose tissue is one of the most spread tissues; it forms fat depots, varied in their structural and functional characteristics. Adipose tissue is plastic. During human’s life, it undergoes many changes and restructuring. With age, the proportion of different types of adipose tissue and the microenvironment of adipocytes change, including the stromal component, immune cells and the microcirculation. In addition, energy storage strategies differ between younger and older adults. A redistribution of adipose tissue into visceral depots is observed even in patients with adequate body mass index. These changes aggravate metabolic disorders and contribute to insulin resistance. Along with increased proinflammatory potential and endothelial dysfunction, aging of adipose tissue increases the risk of cardiovascular outcomes. At the same time, the described changes are also observed in obesity, even in relatively young patients. It is assumed that the peculiarities of lipid accumulation due to adipocyte hypertrophy entail the development of dysfunction of adipose tissue, which is reflected in changes in its cytokine and hormonal profile. Such pathological processes are characteristic of the so-called “metabolically unhealthy” obesity.
This review provides current knowledge about the changes that different types of adipose tissue undergo over time, as well as the connection between pathophysiological processes and clinical manifestations observed with aging and dysfunction of adipose tissue.

Keywords

obesity, white adipose tissue, brown adipose tissue, aging, adipogenesis, metabolically benign obesity

About the Authors

G. V. Semikova

Pavlov First Saint Petersburg State Medical University
Russian Federation

Galina V. Semikova, Candidate of Medical Sciences

197022, St-Petersburg, L. Tolstoy st., 17,
build. 11

Competing Interests:

Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с содержанием настоящей статьи

Yu. Sh. Khalimov

Pavlov First Saint Petersburg State Medical University
Russian Federation

Yuri Sh. Khalimov, Doctor of Medical Sciences

Saint Petersburg

Competing Interests:

A. R. Volkova

Pavlov First Saint Petersburg State Medical University
Russian Federation

Anna R. Volkova, Doctor of Medical Sciences

Saint Petersburg

Competing Interests:

References

1. Ghaben AL, Scherer PE. Adipogenesis and metabolic health. Nat Rev Mol Cell Biol. 2019. doi: https://doi.org/10.1038/s41580-018-0093-z

2. Ambele MA, Dhanraj P, Giles R, Pepper MS. Adipogenesis: A Complex Interplay of Multiple Molecular Determinants and Pathways. Int J Mol Sci. 2020;21(12):4283. doi: https://doi.org/10.3390/ijms21124283

3. Liu Z, Wu KKL, Jiang X, Xu A, Cheng KKY. The role of adipose tissue senescence in obesity- and ageing-related metabolic disorders. Clin Sci. 2020;134(2):315-330. doi: https://doi.org/10.1042/CS20190966

4. Tchkonia T, Morbeck DE, Von Zglinicki T, et al. Fat tissue, aging, and cellular senescence. Aging Cell. 2010. doi: https://doi.org/10.1111/j.1474-9726.2010.00608.x

5. Ibrahim MM. Subcutaneous and visceral adipose tissue: structural and functional differences. Obes Rev. 2010;11(1):11-18. doi: https://doi.org/10.1111/j.1467-789X.2009.00623.x

6. Kahn CR, Wang G, Lee KY. Altered adipose tissue and adipocyte function in the pathogenesis of metabolic syndrome. J Clin Invest. 2019;129(10):3990-4000. doi: https://doi.org/10.1172/JCI129187

7. Romantsova TI. Adipose tissue: colors, depots and functions. Obesity and metabolism. 2021;18(3):282-301. (In Russ.) doi: https://doi.org/10.14341/omet12748

8. Chait A, den Hartigh LJ. Adipose Tissue Distribution, Inflammation and Its Metabolic Consequences, Including Diabetes and Cardiovascular Disease. Front Cardiovasc Med. 2020;7. doi: https://doi.org/10.3389/fcvm.2020.00022

9. Afanaskina L.N., Derevtsova S.N., Sindeeva L.V. et al. Brown adipose tissue: features of biology, participation in energy metabolism and obesity. Annals of the Russian Academy of Medical Sciences. 2020;75(4):326–330. (In Russ.) doi: http://doi.org/10.15690/vramn1316

10. Myadelets O.D., Myadelets V.O., Sobolevskaya I.S., et al. White and brown adipose tissue: interaction with skeletal muscle tissue // Annals of VGMU . 2014;13(5):35-44 (In Russ.)

11. Shankar K, Kumar D, Gupta S, et al. Role of brown adipose tissue in modulating adipose tissue inflammation and insulin resistance in high-fat diet fed mice. Eur J Pharmacol. 2019;854:354-364. doi: https://doi.org/10.1016/j.ejphar.2019.02.044

12. Peirce V, Vidal-Puig A. Regulation of glucose homoeostasis by brown adipose tissue. Lancet Diabetes Endocrinol. 2013;1(4):353-360. doi: https://doi.org/10.1016/S2213-8587(13)70055-X

13. Bredella MA, Gill CM, Rosen CJ, Klibanski A, Torriani M. Positive effects of brown adipose tissue on femoral bone structure. Bone. 2014;58:55-58. doi: https://doi.org/10.1016/j.bone.2013.10.007

14. Maliszewska K, Kretowski A. Brown adipose tissue and its role in insulin and glucose homeostasis. Int J Mol Sci. 2021. doi: https://doi.org/10.3390/ijms22041530

15. López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The Hallmarks of Aging. Cell. 2013;153(6):1194-1217. doi: https://doi.org/10.1016/j.cell.2013.05.039

16. Piya MK, McTernan PG, Kumar S. Adipokine inflammation and insulin resistance: the role of glucose, lipids and endotoxin. J Endocrinol. 2013;216(1):T1-T15. doi: https://doi.org/10.1530/JOE-12-0498

17. Schaum N, Lehallier B, Hahn O, et al. Ageing hallmarks exhibit organ-specific temporal signatures. Nature. 2020;583(7817):596-602. doi: https://doi.org/10.1038/s41586-020-2499-y

18. Smith U, Li Q, Rydén M, Spalding KL. Cellular senescence and its role in white adipose tissue. Int J Obes. 2021;45(5):934-943. doi: https://doi.org/10.1038/s41366-021-00757-x

19. Murano I, Barbatelli G, Parisani V, et al. Dead adipocytes, detected as crown-like structures, are prevalent in visceral fat depots of genetically obese mice. J Lipid Res. 2008;49(7):1562-1568. doi: https://doi.org/10.1194/jlr.M800019-JLR200

20. Frasca D, Diaz A, Romero M, Landin AM, Blomberg BB. High TNF-α levels in resting B cells negatively correlate with their response. Exp Gerontol. 2014;54:116-122. doi: https://doi.org/10.1016/j.exger.2014.01.004

21. Higuchi M, Dusting GJ, Peshavariya H, et al. Differentiation of human adipose-derived stem cells into fat involves reactive oxygen species and forkhead box o1 mediated upregulation of antioxidant enzymes. Stem Cells Dev. 2013. doi: https://doi.org/10.1089/scd.2012.0306

22. Dludla P V., Nkambule BB, Jack B, et al. Inflammation and oxidative stress in an obese state and the protective effects of gallic acid. Nutrients. 2019. doi: https://doi.org/10.3390/nu11010023

23. Raguso CA, Kyle U, Kossovsky MP, et al. A 3-year longitudinal study on body composition changes in the elderly: Role of physical exercise. Clin Nutr. 2006;25(4):573-580. doi: https://doi.org/10.1016/j.clnu.2005.10.013

24. Zamboni M, Rossi AP, Fantin F, et al. Adipose tissue, diet and aging. Mech Ageing Dev. 2014;136-137:129-137. doi: https://doi.org/10.1016/j.mad.2013.11.008

25. Corrales P, Martín-Taboada M, Medina-Gomez G. The risk of jiggly fat in aging. Aging (Albany NY). 2019;11(15):5298-5299. doi: https://doi.org/10.18632/aging.102147

26. Ambikairajah A, Walsh E, Tabatabaei-Jafari H, Cherbuin N. Fat mass changes during menopause: a metaanalysis. Am J Obstet Gynecol. 2019. doi: https://doi.org/10.1016/j.ajog.2019.04.023

27. Park SE, Park CY, Choi JM, et al. Depot-specific changes in fat metabolism with aging in a type 2 diabetic animal model. PLoS One. 2016. doi: https://doi.org/10.1371/journal.pone.0148141

28. Kim SM, Lun M, Wang M, et al. Loss of White Adipose Hyperplastic Potential Is Associated with Enhanced Susceptibility to Insulin Resistance. Cell Metab. 2014;20(6):1049-1058. doi: https://doi.org/10.1016/j.cmet.2014.10.010

29. Bielczyk-Maczynska E. White adipocyte plasticity in physiology and disease. Cells. 2019. doi: https://doi.org/10.3390/cells8121507 30. Rosen ED, Spiegelman BM. What We Talk About When We Talk About Fat. Cell. 2014;156(1-2):20-44. doi: https://doi.org/10.1016/j.cell.2013.12.012

30. Hammarstedt A, Gogg S, Hedjazifar S, Nerstedt A, Smith U. Impaired Adipogenesis and Dysfunctional Adipose Tissue in Human Hypertrophic Obesity. Physiol Rev. 2018;98(4):1911-1941. doi: https://doi.org/10.1152/physrev.00034.2017

31. Corrales P, Vivas Y, Izquierdo‐Lahuerta A, et al. Long‐term caloric restriction ameliorates deleterious effects of aging on white and brown adipose tissue plasticity. Aging Cell. 2019;18(3). doi: https://doi.org/10.1111/acel.12948

32. Schoettl T, Fischer IP, Ussar S. Heterogeneity of adipose tissue in development and metabolic function. Suarez RK, Hoppeler HH, eds. J Exp Biol. 2018;221(Suppl_1). doi: https://doi.org/10.1242/jeb.162958

33. Tchkonia T, Thomou T, Zhu Y, et al. Mechanisms and Metabolic Implications of Regional Differences among Fat Depots. Cell Metab. 2013;17(5):644-656. doi: https://doi.org/10.1016/j.cmet.2013.03.008

34. Tchernof A, Després J-P. Pathophysiology of Human Visceral Obesity: An Update. Physiol Rev. 2013;93(1):359-404. doi: https://doi.org/10.1152/physrev.00033.2011

35. Frasca D, Blomberg BB. Adipose tissue, immune aging, and cellular senescence. Semin Immunopathol. 2020;42(5):573-587. doi: https://doi.org/10.1007/s00281-020-00812-1

36. Finelli C, Sommella L, Gioia S, La Sala N, Tarantino G. Should visceral fat be reduced to increase longevity? Ageing Res Rev. 2013;12(4):996-1004. doi: https://doi.org/10.1016/j.arr.2013.05.007

37. Koster A, Murphy RA, Eiriksdottir G, et al. Fat distribution and mortality: The AGES‐Reykjavik study. Obesity. 2015;23(4):893-897. doi: https://doi.org/10.1002/oby.21028

38. Sawaki D, Czibik G, Pini M, et al. Visceral Adipose Tissue Drives Cardiac Aging Through Modulation of Fibroblast Senescence by Osteopontin Production. Circulation. 2018;138(8):809-822. doi: https://doi.org/10.1161/CIRCULATIONAHA.117.031358

39. Rossi AP, Watson NL, Newman AB, et al. Effects of Body Composition and Adipose Tissue Distribution on Respiratory Function in Elderly Men and Women: The Health, Aging, and Body Composition Study. Journals Gerontol Ser A Biol Sci Med Sci. 2011;66A(7):801-808. doi: https://doi.org/10.1093/gerona/glr059

40. Debette S, Beiser A, Hoffmann U, et al. Visceral fat is associated with lower brain volume in healthy middle‐aged adults. Ann Neurol. 2010;68(2):136-144. doi: https://doi.org/10.1002/ana.22062

41. Chiba I, Lee S, Bae S, Makino K, Shinkai Y, Shimada H. Visceral Fat Accumulation is Associated with Mild Cognitive Impairment in Community-Dwelling Older Japanese Women. J Nutr Heal aging. 2020;24(3):352-357. doi: https://doi.org/10.1007/s12603-020-1330-7

42. Nyberg CK, Fjell AM, Walhovd KB. Level of body fat relates to memory decline and interacts with age in its association with hippocampal and subcortical atrophy. Neurobiol Aging. 2020;91:112-124. doi: https://doi.org/10.1016/j.neurobiolaging.2019.10.005

43. Shin JA, Jeong SI, Kim M, Yoon JC, Kim H-S, Park E-M. Visceral adipose tissue inflammation is associated with age-related brain changes and ischemic brain damage in aged mice. Brain Behav Immun. 2015;50:221-231. doi: https://doi.org/10.1016/j.bbi.2015.07.008

44. Graja A, Gohlke S, Schulz TJ. Aging of Brown and Beige/Brite Adipose Tissue. In: Handbook of Experimental Pharmacology. ; 2018:55-72. doi: https://doi.org/10.1007/164_2018_151

45. Gao P, Jiang Y, Wu H, et al. Inhibition of mitochondrial calcium overload by SIRT3 prevents obesity-or age related whitening of brown adipose tissue. Diabetes. 2020. doi: https://doi.org/10.2337/db19-0526

46. Becher T, Palanisamy S, Kramer DJ, et al. Brown adipose tissue is associated with cardiometabolic health. Nat Med. 2021;27(1):58-65. doi: https://doi.org/10.1038/s41591-020-1126-7

47. Sellayah D, Sikder D. Orexin restores aging-related brown adipose tissue dysfunction in male mice. Endocrinology. 2014. doi: https://doi.org/10.1210/en.2013-1629

48. Gonçalves LF, Machado TQ, Castro-Pinheiro C, de Souza NG, Oliveira KJ, Fernandes-Santos C. Ageing is associated with brown adipose tissue remodelling and loss of white fat browning in female C57BL/6 mice. Int J Exp Pathol. 2017. doi: https://doi.org/10.1111/iep.12228

49. van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, et al. Cold-Activated Brown Adipose Tissue in Healthy Men. N Engl J Med. 2009;360(15):1500-1508. doi: https://doi.org/10.1056/NEJMoa0808718

50. Sakamoto T, Nitta T, Maruno K, et al. Macrophage infiltration into obese adipose tissues suppresses the induction of UCP1 level in mice. Am J Physiol - Endocrinol Metab. 2016. doi: https://doi.org/10.1152/ajpendo.00028.2015

51. Graja A, Schulz TJ. Mechanisms of Aging-Related Impairment of Brown Adipocyte Development and Function. Gerontology. 2015;61(3):211-217. doi: https://doi.org/10.1159/000366557

52. Fitzgibbons TP, Kogan S, Aouadi M, Hendricks GM, Straubhaar J, Czech MP. Similarity of mouse perivascular and brown adipose tissues and their resistance to diet induced inflammation. Am J Physiol - Hear Circ Physiol. 2011. doi: https://doi.org/10.1152/ajpheart.00376.2011

53. Volkova NI, Porksheyan MI, Gyulmagomedova AN. Brown adipose tissue in adults: consensus points and guidelines for future experiments. Medical Herald of the South of Russia. 2016;(3):4-13. (In Russ.) doi: https://doi.org/10.21886/2219-8075-2016-3-4-13

54. Yu H, Dilbaz S, Coßmann J, et al. Breast milk alkylglycerols sustain beige adipocytes through adipose tissue macrophages. J Clin Invest. 2019. doi: https://doi.org/10.1172/JCI125646

Supplementary files

	1. Figure 1. Distribution and functions of the fat depots in the human body.
	Subject
	Type	Исследовательские инструменты
	View (854KB)	Indexing metadata ▾

	2. Figure 2. Adipogenesis in adults (adapted from Ghaben, 2019).
	Subject
	Type	Исследовательские инструменты
	View (812KB)	Indexing metadata ▾

	3. Figure 3. Effects of aging and obesity on white adipose tissue.
	Subject
	Type	Исследовательские инструменты
	View (818KB)	Indexing metadata ▾

	4. Figure 4. Detection of brown adipose tissue according to 18F-FDG PET-CT in patients with different body weights in the van Marken Lichtenbelt WD study (2009) [47].
	Subject
	Type	Исследовательские инструменты
	View (439KB)	Indexing metadata ▾

	5. Figure 5. Mechanisms of metabolically healthy and unhealthy obesity. Adapted from Ghaben (2019).
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	Type	Исследовательские инструменты
	View (315KB)	Indexing metadata ▾

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Semikova G.V., Khalimov Yu.Sh., Volkova A.R. Adipose tissue aging: pathophysiological and clinical aspects. Obesity and metabolism. 2025;22(1):41-51. (In Russ.) https://doi.org/10.14341/omet13069

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	Title	Figure 1. Distribution and functions of the fat depots in the human body.
	Type	Исследовательские инструменты
	Date	2025-05-25
Digital Object Identifier	https://doi.org/10.14341/omet13069-6681

	Title	Figure 2. Adipogenesis in adults (adapted from Ghaben, 2019).
	Type	Исследовательские инструменты
	Date	2025-05-25
Digital Object Identifier	https://doi.org/10.14341/omet13069-6682

	Title	Figure 3. Effects of aging and obesity on white adipose tissue.
	Type	Исследовательские инструменты
	Date	2025-05-25
Digital Object Identifier	https://doi.org/10.14341/omet13069-6683

	Title	Figure 4. Detection of brown adipose tissue according to 18F-FDG PET-CT in patients with different body weights in the van Marken Lichtenbelt WD study (2009) [47].
	Type	Исследовательские инструменты
	Date	2025-05-25
Digital Object Identifier	https://doi.org/10.14341/omet13069-6684

	Title	Figure 5. Mechanisms of metabolically healthy and unhealthy obesity. Adapted from Ghaben (2019).
	Type	Исследовательские инструменты
	Date	2025-05-25
Digital Object Identifier	https://doi.org/10.14341/omet13069-6685

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Obesity and metabolism

Adipose tissue aging: pathophysiological and clinical aspects

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