Biomarkers of Age-Related Frailty and Frailty Related to Disease

D. Angioni (1, 2) , W.H. Lu (1) , S. Sourdet (1) , T. Macaron (1) , C. Takeda (1) , S. Guyonnet (2, 1) , J.F. Mangin (3, 4) , Y. Rolland (2, 1) , P. de Souto Barreto (1) , B. Vellas (2, 1)

1 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
2 Equipe Vieillissement (CERPOP)
3 BAOBAB - Building large instruments for neuroimaging: from population imaging to ultra-high magnetic fields
4 SU - Sorbonne Université

Background: Frailty may in most cases result from two main causes: the aging process (age-related frailty) and diseases (evolving chronic conditions or acute medical illnesses - disease-related frailty). The biological determinants characterizing these two main causes of frailty may be different. Objectives: The aim of this study is to compare the biological and neuroimaging profile of people without frailty, those with age-related frailty, and subjects with disease-related frailty in community-dwelling older adults. Material and methods: We performed a secondary, cross-sectional analysis from the Multidomain Alzheimer Preventive Trial (MAPT). We included 1199 subjects without frailty throughout the 5-year follow-up, 82 subjects with incident age-related frailty, and 53 with incident disease-related frailty. Available blood biomarkers involved nutritional (eg, vitamin D, omega-3 fatty acids), inflammatory-related (IL-6, TNFR1, GDF15), neurodegenerative (eg, beta-amyloid, neurofilament light chain) and neuroimaging markers (MRI, Amyloid-PET). Results: Although not statistically significant, the results of the unadjusted model showed increasing gradients for inflammatory markers (GDF15, TNFR1) and decreasing gradients for nutritional and neuroimaging markers (omega 3 index, hippocampal volume) from age-related frailty participants to individuals with disease-related frailty. Considering the linear models we observed higher GDF15 values in disease-related frailty group compared to age-related frailty individuals [β = 242.8 (49.5, 436.2)]. We did not find any significant difference between subjects without frailty and those with age-related frailty. Subjects with disease-related frailty compared to subjects without frailty had lower values of DHA [β = -2.42 (-4.76, -0.08)], Omega 3 Index [β = -0.50 (-0.95, -0.06)] and hippocampal volume [β = -0.22 (-0.42,-0.02)]. They also had higher values of GDF15 [β = 246.1 (88.9, 403.4)] and TNFR1 [β = 157.5 (7.8, 307.2)]. Conclusion: Age-related frailty and disease-related frailty may represent different degrees of frailty severity on a biological level. Further research is needed to identify biomarkers potentially able to distinguish these classifications of frailty.

Mots clés: Frailty related to diseases; age-related frailty; biomarkers; geroscience

Domaines: Sciences du Vivant [q-bio]

D. Angioni, W.H. Lu, S. Sourdet, T. Macaron, C. Takeda, et al.. Biomarkers of Age-Related Frailty and Frailty Related to Disease: An Exploratory, Cross-Sectional Analysis from the MAPT Study. Journal of Nutrition, Health & Aging, 2022, 26 (6), pp.545-551. ⟨10.1007/s12603-022-1793-9⟩. ⟨hal-04419850⟩