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Sayed, N., Huang, Y., & Nguyen, K. (2021). An inflammatory aging clock (iAge) based on deep learning tracks multimorbidity, immunosenescence, frailty and cardiovascular aging. Nature aging, 1, 598–615. 
Added by: Dr. Enrique Feoli (28/04/2023, 16:57)   Last edited by: Dr. Enrique Feoli (28/04/2023, 17:18)
Resource type: Journal Article
DOI: 10.1038/s43587-021-00082-y
ID no. (ISBN etc.): 2662-8465
BibTeX citation key: Sayed2021
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 Categories: BioAcyl Corp
Subcategories: Ageing
Creators: Huang, Nguyen, Sayed
Collection: Nature aging		 Views: 3/133
Abstract
While many diseases of aging have been linked to the immunological system, immune metrics capable of identifying the most at-risk individuals are lacking. From the blood immunome of 1,001 individuals aged 8–96 years, we developed a deep-learning method based on patterns of systemic age-related inflammation. The resulting inflammatory clock of aging (iAge) tracked with multimorbidity, immunosenescence, frailty and cardiovascular aging, and is also associated with exceptional longevity in centenarians. The strongest contributor to iAge was the chemokine CXCL9, which was involved in cardiac aging, adverse cardiac remodeling and poor vascular function. Furthermore, aging endothelial cells in human and mice show loss of function, cellular senescence and hallmark phenotypes of arterial stiffness, all of which are reversed by silencing CXCL9. In conclusion, we identify a key role of CXCL9 in age-related chronic inflammation and derive a metric for multimorbidity that can be utilized for the early detection of age-related clinical phenotypes.
  
Notes

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1000 Immunomes Study design: systematic analysis of immune systems via ‘OMiCS’ approaches. The Stanford 1000 Immunomes Project consist of 1001 ambulatory subjects age 8 to 96 (34% males, 66% females) recruited during the years 2007 to 2016 for a longitudinal study of aging and vaccination, and for an independent study of chronic fatigue syndrome from which only healthy controls were included. For all samples of the Stanford 1KIP, deep immune phenotyping was conducted at the Stanford Human Immune Monitoring Center, where peripheral blood specimens were isolated and analyzed using standard procedures. Peripheral blood samples were obtained by venipuncture and peripheral blood mononuclear cells or whole blood samples were used for determination of cellular phenotypes and frequencies (N = 935) and for investigation of in vitro cellular responses to a variety of cytokine stimulations (N = 818); serum samples were obtained and used for protein content determination (including a total of 50 cytokines, chemokines and growth factors) (N = 1001). Clinical characterization was assessed via clinical questionnaire in a total of 902 subjects who completed the full set of 53 clinical items. From a total of 97 healthy young and older adults, comprehensive cardiovascular phenotyping was also conducted
Added by: Dr. Enrique Feoli  Last edited by: Dr. Enrique Feoli
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