| First Author | Sawaki D | Year | 2023 |
| Journal | JCI Insight | Volume | 8 |
| Issue | 8 | PubMed ID | 37092554 |
| Mgi Jnum | J:346273 | Mgi Id | MGI:7489078 |
| Doi | 10.1172/jci.insight.145811 | Citation | Sawaki D, et al. (2023) Osteopontin promotes age-related adipose tissue remodeling through senescence-associated macrophage dysfunction. JCI Insight 8(8) |
| abstractText | Adipose tissue macrophages (ATMs) play an important role in obesity and inflammation, and they accumulate in adipose tissue (AT) with aging. Furthermore, increased ATM senescence has been shown in obesity-related AT remodeling and dysfunction. However, ATM senescence and its role are unclear in age-related AT dysfunction. Here, we show that ATMs (a) acquire a senescence-like phenotype during chronological aging; (b) display a global decline of basic macrophage functions such as efferocytosis, an essential process to preserve AT homeostasis by clearing dysfunctional or apoptotic cells; and (c) promote AT remodeling and dysfunction. Importantly, we uncover a major role for the age-associated accumulation of osteopontin (OPN) in these processes in visceral AT. Consistently, loss or pharmacologic inhibition of OPN and bone marrow transplantation of OPN-/- mice attenuate the ATM senescence-like phenotype, preserve efferocytosis, and finally restore healthy AT homeostasis in the context of aging. Collectively, our findings implicate pharmacologic OPN inhibition as a viable treatment modality to counter ATM senescence-mediated AT remodeling and dysfunction during aging. |
