AI Article Synopsis

  • Obesity in older adults is prevalent and contributes to chronic inflammation, affecting the health of older populations.
  • Research suggests that obesity alters the immune response, particularly influencing T-cell function and the effectiveness of anti-inflammatory drugs like metformin.
  • Data reveal that metformin does not improve immune cell function in obese older adults as it does in lean individuals, indicating that obesity complicates the body's inflammatory response and must be considered in clinical studies of geroprotective treatments.

Article Abstract

The alarmingly high prevalence of obesity in older adults coupled with the negative health effects of chronic inflammation in both obesity and aging highlight the importance of studies investigating the impacts of obesity on age-related inflammation. Since shifts in peripheral T-cell metabolism and function drive systemic inflammation in both obesity and aging, we hypothesize that obesity impacts the Th17-dominated inflammaging profile we identified in lean subjects and thus modifies the anti-inflammatory effects of geroprotective drugs like metformin. New cytokine profiling data showed that CD4 T cells from older people with obesity generate a profile that specifically excludes Th17 cytokines. Metformin failed to change the age-associated T-cell profile in obesity, despite lowering both mitochondrial respiration and reactive oxygen species (ROS) production. Metformin did not improve macroautophagy in T cells from older people with obesity, in sharp contrast to the ability of metformin to promote autophagy in T cells from older lean subjects. These data indicate that body mass index modifies the mechanisms supporting inflammaging in T cells from older subjects, and that metformin-mediated restoration of redox balance is insufficient to stem obesity-associated inflammaging. We conclude that obesity fundamentally changes the mechanisms that promote inflammaging, and thus obesity becomes a critical consideration for clinical trials of geroprotective agents such as metformin.

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http://dx.doi.org/10.1007/s11357-024-01441-4DOI Listing

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  • Obesity in older adults is prevalent and contributes to chronic inflammation, affecting the health of older populations.
  • Research suggests that obesity alters the immune response, particularly influencing T-cell function and the effectiveness of anti-inflammatory drugs like metformin.
  • Data reveal that metformin does not improve immune cell function in obese older adults as it does in lean individuals, indicating that obesity complicates the body's inflammatory response and must be considered in clinical studies of geroprotective treatments.
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