Abstract
Cold temperatures induce progenitor cells within white adipose tissue to form beige adipocytes that burn energy and generate heat; this is a potential anti-diabesity therapy. However, the potential to form cold-induced beige adipocytes declines with age. This creates a clinical roadblock to potential therapeutic use in older individuals, who constitute a large percentage of the obesity epidemic. Here we show that aging murine and human beige progenitor cells display a cellular aging, senescence-like phenotype that accounts for their age-dependent failure. Activating the senescence pathway, either genetically or pharmacologically, in young beige progenitors induces premature cellular senescence and blocks their potential to form cold-induced beige adipocytes. Conversely, genetically or pharmacologically reversing cellular aging by targeting the p38/MAPK-p16Ink4a pathway in aged mouse or human beige progenitor cells rejuvenates cold-induced beiging. This in turn increases glucose sensitivity. Collectively, these data indicate that anti-aging or senescence modalities could be a strategy to induce beiging, thereby improving metabolic health in aging humans.
Original language | English (US) |
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Pages (from-to) | 166-181 |
Number of pages | 16 |
Journal | Cell Metabolism |
Volume | 25 |
Issue number | 1 |
DOIs | |
State | Published - Jan 10 2017 |
Keywords
- Ink4a/Arf
- adipose
- beige adipocytes
- cellular aging
- cold exposure
- mural cells
- senescence
- thermogenesis
ASJC Scopus subject areas
- Physiology
- Molecular Biology
- Cell Biology