Cellular Senescence in Obesity and Associated Complications: a New Therapeutic Target

Research output: Contribution to journalReview articlepeer-review

Abstract

PURPOSE OF REVIEW: Obesity has increased worldwide recently and represents a major global health challenge. This review focuses on the obesity-associated cellular senescence in various organs and the role of these senescent cells (SnCs) in driving complications associated with obesity. Also, the ability to target SnCs pharmacologically with drugs termed senotherapeutics as a therapy for these complications is discussed.

RECENT FINDINGS: Several studies have shown a positive correlation between obesity and SnC burden in organs such as adipose tissue, liver, and pancreatic-β-cells. These SnCs produce several secretory factors which affect other cells and tissues in a paracrine manner resulting in organ dysfunction. The accumulation of SnCs in adipocytes affects their lipid storage and impairs adipogenesis. The inflammatory senescence-associated secretory phenotype (SASP) of SnCs downregulates the antioxidant capacity and mitochondrial function in tissues. Senescent hepatocytes cannot oxidize fatty acids, which leads to lipid deposition and senescence in β-cells decrease function. These and other adverse effects of SnCs contribute to insulin resistance and type-2 diabetes. The reduction in the SnC burden genetically or pharmacologically improves the complications associated with obesity. The accumulation of SnCs with age and disease accelerates aging. Obesity is a key driver of SnC accumulation, and the complications associated with obesity can be controlled by reducing the SnC burden. Thus, senotherapeutic drugs have the potential to be an effective therapeutic option.

Original languageEnglish (US)
Pages (from-to)537-548
Number of pages12
JournalCurrent diabetes reports
Volume22
Issue number11
DOIs
StatePublished - Nov 2022

Bibliographical note

Funding Information:
This work was supported by NIH grants RO1 AG063543-02S1, P01 AG043376, U19 AG056278, RO1 AG063543, P01 AG062413, U54 AG076041, R01 AG069819, R01 AG063543-S1, and R00 AG058800; an Aligning Science Across Parkinson’s grant ASAP-000592 from the Michael J. Fox Foundation; and the Glenn Foundation for Medical Research.

Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Keywords

  • Humans
  • Antioxidants
  • Senotherapeutics
  • Cellular Senescence/genetics
  • Obesity/complications
  • Fatty Acids
  • Lipids

PubMed: MeSH publication types

  • Review
  • Journal Article

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