Oxysterol Signatures Distinguish Age-Related Macular Degeneration from Physiologic Aging

Jonathan B. Lin, Abdoulaye Sene, Andrea Santeford, Hideji Fujiwara, Rohini Sidhu, Marianne M. Ligon, Vikram A. Shankar, Norimitsu Ban, Indira U. Mysorekar, Daniel S. Ory, Rajendra S. Apte

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Macrophage aging is pathogenic in numerous diseases, including age-related macular degeneration (AMD), a leading cause of blindness in older adults. Although prior studies have explored the functional consequences of macrophage aging, less is known about its cellular basis or what defines the transition from physiologic aging to disease. Here, we show that despite their frequent self-renewal, macrophages from old mice exhibited numerous signs of aging, such as impaired oxidative respiration. Transcriptomic profiling of aged murine macrophages revealed dysregulation of diverse cellular pathways, especially in cholesterol homeostasis, that manifested in altered oxysterol signatures. Although the levels of numerous oxysterols in human peripheral blood mononuclear cells and plasma exhibited age-associated changes, plasma 24-hydroxycholesterol levels were specifically associated with AMD. These novel findings demonstrate that oxysterol levels can discriminate disease from physiologic aging. Furthermore, modulation of cholesterol homeostasis may be a novel strategy for treating age-associated diseases in which macrophage aging is pathogenic.

Original languageEnglish
Pages (from-to)9-20
Number of pages12
StatePublished - Jun 2018


  • Age-related macular degeneration
  • Aging
  • Cholesterol
  • Lipids


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