Covarrubias · Nature metabolism 2020 · preclinical mechanistic study · n=?

Senescent cells promote tissue NAD + decline during ageing via the activation of CD38 + macrophages.

Cited 418 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Preclinical laboratory mechanistic research without clinical data

PubMed 33199924 · doi:10.1038/s42255-020-00305-3 · record verified 2026-08-29

What was done

Investigated the mechanisms connecting cellular senescence, macrophage accumulation, and tissue NAD+ decline during aging and acute inflammation, specifically examining CD38 expression and NADase activity across macrophage subtypes in metabolic tissues including visceral white adipose tissue and liver.

What was found

The abstract reports no numerical values, sample sizes, or effect estimates. It reports that pro-inflammatory M1-like macrophages (unlike naive or M2 macrophages) accumulate in visceral white adipose tissue and liver during aging and inflammation, exhibit elevated CD38 expression and CD38-dependent NADase activity, and drive tissue NAD decline. Additionally, senescent cell secretions (SASP) were found to induce macrophage proliferation and CD38 expression.

Why it matters

Identifies a mechanistic pathway linking senescent cell accumulation to macrophage-driven CD38 NADase activity and subsequent tissue NAD+ depletion during aging.

Limits

The abstract contains no quantitative data, sample sizes, or species details. Findings are purely preclinical and bench-based without direct human clinical trial verification.

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