A single nuclei atlas of aging human abdominal subcutaneous white adipose tissue

Abstract White adipose tissue (WAT) is a robust energy storage and endocrine organ critical for maintaining metabolic health as we age. Our aim was to identify cell-specific transcriptional aberrations that occur in WAT with aging. We leveraged full-length snRNA-Seq to characterize the cellular landscape of human subcutaneous WAT in a prospective cohort of 10 Younger (≤ 30 years) and 10 Older individuals (≥ 65 years) balanced for sex and body mass index (BMI). We highlight that aging WAT is associated with adipocyte hypertrophy, increased proportions of resident macrophages (M2), an upregulated innate immune response and senescence profiles in specific adipocyte populations, highlighting CXCL14 as a biomarker of this process. We also identify novel markers of pre-adipocytes and track their expression levels through pre-adipocyte differentiation. We propose that aging WAT is associated with low-grade inflammation that is managed by a foundation of innate immunity to preserve the metabolic health of the WAT.