TY - JOUR
T1 - An inflammatory aging clock (iAge) based on deep learning tracks multimorbidity, immunosenescence, frailty and cardiovascular aging
AU - Sayed, Nazish
AU - Huang, Yingxiang
AU - Nguyen, Khiem
AU - Krejciova-Rajaniemi, Zuzana
AU - Grawe, Anissa P.
AU - Gao, Tianxiang
AU - Tibshirani, Robert
AU - Hastie, Trevor
AU - Alpert, Ayelet
AU - Cui, Lu
AU - Kuznetsova, Tatiana
AU - Rosenberg-Hasson, Yael
AU - Ostan, Rita
AU - Monti, Daniela
AU - Lehallier, Benoit
AU - Shen-Orr, Shai S.
AU - Maecker, Holden T.
AU - Dekker, Cornelia L.
AU - Wyss-Coray, Tony
AU - Franceschi, Claudio
AU - Jojic, Vladimir
AU - Haddad, François
AU - Montoya, José G.
AU - Wu, Joseph C.
AU - Davis, Mark M.
AU - Furman, David
N1 - Publisher Copyright: © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2021/7
Y1 - 2021/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85113296257&partnerID=8YFLogxK
U2 - 10.1038/s43587-021-00082-y
DO - 10.1038/s43587-021-00082-y
M3 - مقالة
SN - 2662-8465
VL - 1
SP - 598
EP - 615
JO - Nature aging
JF - Nature aging
IS - 7
ER -