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Review
. 2022 Apr 4;13(4):300.
doi: 10.1038/s41419-022-04752-6.

Adipose tissue aging: mechanisms and therapeutic implications

Min-Yi Ou #  1 , Hao Zhang #  1 , Poh-Ching Tan  1 , Shuang-Bai Zhou  2 , Qing-Feng Li  3
Affiliations
Review

Adipose tissue aging: mechanisms and therapeutic implications

Min-Yi Ou et al. Cell Death Dis. .

Abstract

Adipose tissue, which is the crucial energy reservoir and endocrine organ for the maintenance of systemic glucose, lipid, and energy homeostasis, undergoes significant changes during aging. These changes cause physiological declines and age-related disease in the elderly population. Here, we review the age-related changes in adipose tissue at multiple levels and highlight the underlying mechanisms regulating the aging process. We also discuss the pathogenic pathways of age-related fat dysfunctions and their systemic negative consequences, such as dyslipidemia, chronic general inflammation, insulin resistance, and type 2 diabetes (T2D). Age-related changes in adipose tissue involve redistribution of deposits and composition, in parallel with the functional decline of adipocyte progenitors and accumulation of senescent cells. Multiple pathogenic pathways induce defective adipogenesis, inflammation, aberrant adipocytokine production, and insulin resistance, leading to adipose tissue dysfunction. Changes in gene expression and extracellular signaling molecules regulate the aging process of adipose tissue through various pathways. In addition, adipose tissue aging impacts other organs that are infiltrated by lipids, which leads to systemic inflammation, metabolic system disruption, and aging process acceleration. Moreover, studies have indicated that adipose aging is an early onset event in aging and a potential target to extend lifespan. Together, we suggest that adipose tissue plays a key role in the aging process and is a therapeutic target for the treatment of age-related disease, which deserves further study to advance relevant knowledge.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. The age-related redistribution of adipose tissue.
There is a redistribution of WAT mass with advancing age, displayed by increased visceral fat and reduced subcutaneous fat. Yellow represents subcutaneous fat, and red represents visceral fat.
Fig. 2
Fig. 2. Age-related alteration in adipose tissue with dysregulated immune cells, preadipocytes and senescent cells.
In young WAT, APSCs actively proliferate and differentiate to adipocytes. Resident immune cells keep in a relatively stable state. With advancing aging, APSCs gradually lose their developmental potential, leading to low adipogenesis. Aberrant immune cells and senescent cells accumulation drive the aging process of adipose. This figure was created in part with modified BioRender templates.
Fig. 3
Fig. 3. Mechanisms of impaired adipogenesis with aging.
In the aging process, the expression of pro-adipogenic genes, such as C/EBPα and PPARγ, declines in adipose progenitor and stem cells (APSCs), accompanied by increased levels of antiadipogenic factors, including C/EBPβ-LIP, CHOP, and CUGBP1. As a result, old APSCs show a decline in proliferation and differentiation, which leads to low adipogenesis in the elderly. This figure was created in part with modified BioRender templates.
Fig. 4
Fig. 4. The role of adipose tissue in the aging process.
In aging individuals, the adipose tissue can be characterized by tissue redistribution, reduced brown and beige fat, declined APSCs, senescent cell accumulation with SASP, and dysregulated immune cells. Aging adipose impacts the elderly with ectopic lipid and FFA, dysregulated adiponectin, increased proinflammatory cytokines, reduced miRNA synthesis, and high ROS activity. This figure was created in part with modified BioRender templates.
See this image and copyright information in PMC

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