Longitudinal Associations Between ATPase Inhibitory Factor 1, Growth Differentiation Factor-15, and Nutritional Status in Older Adults From the MAPT Study
Authors: Lengelé Laetitia , Rolland Yves , Martinez Laurent O , Guyonnet Sophie , Parini Angelo , Lucas Alexandre , Vellas Bruno , Barreto Philipe de Souto ,   MAPT/DSA Group, Vellas Bruno , Guyonnet Sophie , Carrié Isabelle , Brigitte Lauréane , Faisant Catherine , Lala Françoise , Delrieu Julien , Villars Hélène , Combrouze Emeline , Badufle Carole , Zueras Audrey , Andrieu Sandrine , Cantet Christelle , Morin Christophe , Van Kan Gabor Abellan , Dupuy Charlotte , Rolland Yves , Caillaud Céline , Ousset Pierre-Jean , Lala Françoise , Willis Sherry , Belleville Sylvie , Gilbert Brigitte , Fontaine Francine , Dartigues Jean-François , Marcet Isabelle , Delva Fleur , Foubert Alexandra , Cerda Sandrine , Costes Corinne , Rouaud Olivier , Manckoundia Patrick , Quipourt Valérie , Marilier Sophie , Franon Evelyne , Bories Lawrence , Pader Marie-Laure , Basset Marie-France , Lapoujade Bruno , Faure Valérie , Tong Michael Li Yung , Malick-Loiseau Christine , Cazaban-Campistron Evelyne , Desclaux Françoise , Blatge Colette , Dantoine Thierry , Laubarie-Mouret Cécile , Saulnier Isabelle , Clément Jean-Pierre , Picat Marie-Agnès , Bernard-Bourzeix Laurence , Willebois Stéphanie , Désormais Iléana , Cardinaud Noëlle , Bonnefoy Marc , Livet Pierre , Rebaudet Pascale , Gédéon Claire , Burdet Catherine , Terracol Flavien , Pesce Alain , Roth Stéphanie , Chaillou Sylvie , Louchart Sandrine , Sudres Kristelle , Lebrun Nicolas , Barro-Belaygues Nadège , Touchon Jacques , Bennys Karim , Gabelle Audrey , Romano Aurélia , Touati Lynda , Marelli Cécilia , Pays Cécile , Robert Philippe , Le Duff Franck , Gervais Claire , Gonfrier Sébastien , Gasnier Yannick , Bordes Serge , Begorre Danièle , Carpuat Christian , Khales Khaled , Lefebvre Jean-François , El Idrissi Samira Misbah , Skolil Pierre , Salles Jean-Pierre , Dufouil Carole , Lehéricy Stéphane , Chupin Marie , Mangin Jean-François , Bouhayia Ali , Allard Michèle , Ricolfi Frédéric , Dubois Dominique , Martel Marie Paule Bonceour , Cotton François , Bonafé Alain , Chanalet Stéphane , Hugon Françoise , Bonneville Fabrice , Cognard Christophe , Chollet François , Payoux Pierre , Voisin Thierry , Delrieu Julien , Peiffer Sophie , Hitzel Anne , Allard Michèle , Zanca Michel , Monteil Jacques , Darcourt Jacques , Molinier Laurent , Derumeaux Hélène , Costa Nadège , Perret Bertrand , Vinel Claire , Caspar-Bauguil Sylvie , Olivier-Abbal Pascale , Andrieu Sandrine , Cantet Christelle , Coley Nicola 
Published: October 2023

Abstract

Background
Weight and appetite regulation have been associated with the expression and secretion of ATPase inhibitory factor 1 (IF1) and growth differentiation factor-15 (GDF-15), 2 potential biomarkers for age-related mitochondrial dysfunction. The aim was to explore the associations between these biomarkers and nutritional variables in the Multidomain Alzheimer Preventive Trial study.

Methods
IF1 and GDF-15 plasma levels were quantified at 1-year follow-up. The nutritional status was measured using the Mini Nutritional Assessment (MNA) score variation between baseline and 1- and 2-year visits; appetite loss was extracted from the MNA. Bodyweight was measured every 6 months until the third year and then yearly until the fifth year of follow-up, and weight loss was established if the loss was greater than 5% or 10% within the past 6 or 12 months, respectively. Bidirectional associations of IF1 and GDF-15 levels with malnutrition, appetite, and weight loss were examined. The interactions between individual IF1 and GDF-15 with sex were explored.

Results
Four hundred and forty-eight participants had MNA data and 1 045 had weight loss data. All the associations between IF1 levels and the MNA score, appetite loss, and weight loss were nonsignificant. Higher GDF-15 levels were cross-sectionally associated with appetite loss at the first year of follow-up, and the GDF-15 highest quartile was associated with nearly 80% higher risks of weight loss over 4 years. Interactions between IF1 and GDF-15 levels, and between these 2 markers and sex were not significantly associated with the outcomes.

Conclusions
GDF-15 plasma levels were related to key malnutrition criteria.