Interleukin-6 and C-reactive protein, successful aging, and mortality: the PolSenior study.
BACKGROUND
In the elderly, chronic low-grade inflammation (inflammaging) is a risk factor for the development of aging-related diseases and frailty. Using data from several thousand Eastern Europeans aged 65 years and older, we investigated whether the serum levels of two proinflammatory factors, interleukin-6 (IL-6) and C-reactive protein (CRP), were associated with physical and cognitive performance, and could predict mortality in successfully aging elderly.


RESULTS
IL-6 and CRP levels systematically increased in an age-dependent manner in the entire study group (IL-6: n = 3496 individuals, p < 0.001 and CRP: n = 3632, p = 0.003), and in the subgroup of successfully aging individuals who had never been diagnosed with cardiovascular disease, myocardial infarction, stroke, type 2 diabetes, or cancer, and had a Mini Mental State Examination (MMSE) score ≥24 and a Katz Activities of Daily Living (ADL) score ≥5 (IL-6: n = 1258, p < 0.001 and CRP: n = 1312, p < 0.001). In the subgroup of individuals suffering from aging-related diseases/disability, only IL-6 increased with age (IL-6: n = 2238, p < 0.001 and CRP: n = 2320, p = 0.249). IL-6 and CRP levels were lower in successfully aging individuals than in the remaining study participants (both p < 0.001). Higher IL-6 and CRP levels were associated with poorer physical performance (lower ADL score) and poorer cognitive performance (lower MMSE score) (both p < 0.001). This association remained significant after adjusting for age, gender, BMI, lipids, estimated glomerular filtration rate, and smoking status. Longer survival was associated with lower concentrations of IL-6 and CRP not only in individuals with aging-related diseases/disability (HR = 1.063 per each pg/mL, 95 % CI: 1.052-1.074, p < 0.001 and HR = 1.020 per each mg/L, 95 % CI: 1.015-1.025, p < 0.001, respectively) but also in the successfully aging subgroup (HR = 1.163 per each pg/mL, 95 % CI: 1.128-1.199, p < 0.001 and HR = 1.074 per each mg/L, 95 % CI: 1.047-1.100, p < 0.001, respectively). These associations remained significant after adjusting for age, gender, BMI, lipids and smoking status. The Kaplan-Meier survival curves showed similar results (all p < 0.001).


CONCLUSIONS
Both IL-6 and CRP levels were good predictors of physical and cognitive performance and the risk of mortality in both the entire elderly population and in successfully aging individuals.
Department of Human Epigenetics, Mossakowski Medical Research Centre PAS, 5 Pawinskiego Street, 02-106 Warsaw, Poland ; Department of Geriatrics and Gerontology, Medical Centre of Postgraduate Education, 01-826 Warsaw, Poland.
Monika
M
Puzianowska-Kuźnicka
Department of Human Epigenetics, Mossakowski Medical Research Centre PAS, 5 Pawinskiego Street, 02-106 Warsaw, Poland ; PolSenior Project, International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland.
Magdalena
M
Owczarz
Department of Palliative Medicine, Poznan University of Medical Sciences, 61-245 Poznan, Poland.
Katarzyna
K
Wieczorowska-Tobis
Third Department of Cardiology, Medical University of Silesia in Katowice, 40-635 Katowice, Poland.
Pawel
P
Nadrowski
Department of Pathophysiology, Faculty of Medicine, Medical University of Silesia in Katowice, 40-752 Katowice, Poland ; Deparment of Internal Medicine and Oncological Chemotherapy, Faculty of Medicine, Medical University of Silesia in Katowice, 40-027 Katowice, Poland.
Jerzy
J
Chudek
PolSenior Project, International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland.
Przemyslaw
P
Slusarczyk
Department of Internal Medicine and Geriatrics, Jagiellonian University Medical College, 31-351 Cracow, Poland.
Anna
A
Skalska
Department of Human Epigenetics, Mossakowski Medical Research Centre PAS, 5 Pawinskiego Street, 02-106 Warsaw, Poland.
Marta
M
Jonas
Department of Human Epigenetics, Mossakowski Medical Research Centre PAS, 5 Pawinskiego Street, 02-106 Warsaw, Poland.
Edward
E
Franek
PolSenior Project, International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland.
Malgorzata
M
Mossakowska
Aging; High sensitivity C-reactive protein (CRP); Inflammaging; Interleukin 6 (IL-6); Low-grade inflammation; Mortality; Successful aging; The Katz Activity of Daily Living (ADL); The Mini Mental State Examination (MMSE)