PT  - JOURNAL ARTICLE
AU  - Anthony J. Covarrubias
AU  - Jose Alberto Lopez-Dominguez
AU  - Rosalba Perrone
AU  - Abhijit Kale
AU  - John Newman
AU  - Shankar S. Iyer
AU  - Mark S. Schmidt
AU  - Herbert G. Kasler
AU  - Kyong-Oh Shin
AU  - Yong-Moon Lee
AU  - Issam Ben-Sahra
AU  - Melanie Ott
AU  - Charles Brenner
AU  - Judith Campisi
AU  - Eric Verdin
TI  - Aging-related inflammation driven by cellular senescence enhances NAD consumption via activation of CD38<sup>+</sup> macrophages
AID  - 10.1101/609438
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 609438
4099  - http://biorxiv.org/content/early/2019/04/17/609438.short
4100  - http://biorxiv.org/content/early/2019/04/17/609438.full
AB  - Decline in tissue NAD levels during aging has been linked to aging-associated diseases, such as age-related metabolic disease, physical decline, and Alzheimer’s disease. However, the mechanism for aging-associated NAD decline remains unclear. Here we report that pro-inflammatory M1 macrophages, but not naïve or M2 macrophages, highly express the NAD consuming enzyme CD38 and have enhanced CD38-dependent NADase activity. Furthermore, we show that aging is associated with enhanced inflammation due to increased senescent cells, and the accumulation of CD38 positive M1 macrophages in visceral white adipose tissue. We also find that inflammatory cytokines found in the supernatant from senescent cells (Senescence associated secretory proteins, SASP) induces macrophages to proliferate and express CD38. As senescent cells progressively accumulate in adipose tissue during aging, these results highlight a new causal link between visceral tissue senescence and tissue NAD decline during aging and may present a novel therapeutic opportunity to maintain NAD levels during aging.