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Aging-related inflammation driven by cellular senescence enhances NAD consumption via activation of CD38+ macrophages

ABSTRACT: Decline in tissue NAD levels during aging has been linked to aging-associated diseases, such as age-related metabolic disease, physical decline, and Alzheimers disease. However, the mechanism for aging-associated NAD decline remains unclear. Here we report that pro-inflammatory M1 macrophages, but not naive 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.

INSTRUMENT(S): TripleTOF 6600, TripleTOF 5600

ORGANISM(S): Mus Musculus (ncbitaxon:10090)

SUBMITTER: Birgit Schilling

PROVIDER: MSV000083726 | MassIVE | Thu Apr 25 13:35:00 BST 2019

SECONDARY ACCESSION(S): PXD013639

REPOSITORIES: MassIVE

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