Exercise, lifespan and healthspan: a molecular and longitudinal approach to study their interactions

• Grant number: 17/16540-5
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): November 01, 2017
• Effective date (End): October 31, 2021
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Julio Cesar Batista Ferreira
• Grantee: Juliane Cruz Campos
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 19/18444-9 - Mitochondrial dynamics as a limiting factor of exercise-increased healthspan in Caenorhabditis elegans, BE.EP.PD

Abstract

Sustainability is one of the main topics discussed in the modern societies. A supply-demand imbalance of renewable and non-renewable resources may trigger a social chaos in the mid- to long-term. The exponential increase of elderly population has a major impact on this phenomenon. Paradoxically, continuous increase of life expectancy can result in the bankruptcy of the healthcare systems. In this context, geroscience has been trying to develop strategies capable of extending life in a healthier way by increasing healthspan - the period of life in which an individual manages to maintain a good health. Recent studies have shown that genetic manipulations in the nematode Caenorhabditis elegans (C. elegans), as well as environmental changes, are able to increase lifespan. However, little is known about the relationship between lifespan and healthspan. A life extension not followed by an increased healthspan would be catastrophic and not sustainable for modern societies. A major problem in studying the interaction between lifespan and healthspan, and especially in establishing a causal-relationship, is the lack of robust experimental models. Considering that reduced physical capacity is one of the main barriers for healthy aging, we believe that exercise fits as a powerful tool for both evaluating and achieving healthspan. So, we plan to characterize basal- and induced-locomotor activity as healthspan markers in C. elegans, as well as to study their interactions with lifespan. Furthermore, we propose to investigate the impact of daily exercise on lifespan and healthspan in C. elegans. These data will be validated using long-lived nematodes. Finally, we will perform a functional genomic analysis to identify human orthologs (genes) essential to increase healthspan and lifespan in C. elegans. It is noteworthy that directly screening interventions for lifespan phenotypes in mammals is limited by long lifespans. Our preliminary data are promising and demonstrate that increased lifespan is not always accompanied by improvements in healthspan (i.e. physical capacity and resistance to thermal stress). It is worth mentioning that Alexander Van der Bliek (UCLA-USA), Eyleen O'Rourke (U. Virginia-USA) and Marcelo Mori (Unicamp) will be our collaborators in this project. (AU)

Scientific publications

(7)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

BOZI, LUIZ H. M.; CAMPOS, JULIANE C.; ZAMBELLI, VANESSA O.; FERREIRA, NIKOLAS D.; FERREIRA, JULIO C. B.. Mitochondrially-targeted treatment strategies. MOLECULAR ASPECTS OF MEDICINE, v. 71, FEB 2020. (13/07937-8, 17/16071-5, 18/18627-3, 17/24836-1, 17/16540-5, 17/16694-2, 18/19332-7)

GONCALVES, LIVIA DE SOUZA; SALES, LUCAS PEIXOTO; SAITO, TIEMI RAQUEL; CAMPOS, JULIANE CRUZ; FERNANDES, ALAN LINS; NATALI, JOSE; JENSEN, LEONARDO; ARNOLD, ALEXANDRE; RAMALHO, LISLEY; BECHARA, LUIZ ROBERTO GRASSMANN; et al. Histidine dipeptides are key regulators of excitation-contraction coupling in cardiac muscle: Evidence from a novel CARNS1 knockout rat model. REDOX BIOLOGY, v. 44, AUG 2021. (17/16540-5, 13/14746-4, 17/11142-1, 13/07937-8, 17/13552-2, 19/24899-9, 18/14544-6, 19/25032-9, 14/11948-8, 20/04006-7)

CAMPOS, JULIANE C.; CHEN, CHE-HONG; FERREIRA, JULIO C. B.. Comment on: ``Aldehyde dehydrogenases contribute to skeletal muscle homeostasis in healthy, aging, and Duchenne muscular dystrophy patients{''} by Etienne et al.. JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE, JUL 2020. (15/22814-5, 17/16540-5, 19/25049-9, 19/18444-9)

FERREIRA, JULIO C. B.; CAMPOS, JULIANE C.; QVIT, NIR; QI, XIN; BOZI, LUIZ H. M.; BECHARA, LUIZ R. G.; LIMA, VANESSA M.; QUELICONI, BRUNO B.; DISATNIK, MARIE-HELENE; DOURADO, PAULO M. M.; et al. A selective inhibitor of mitofusin 1-beta IIPKC association improves heart failure outcome in rats. NATURE COMMUNICATIONS, v. 10, JAN 18 2019. (10/00028-4, 15/22814-5, 17/16694-2, 17/11142-1, 12/05765-2, 10/51906-1, 17/16540-5, 09/12349-2, 16/01633-5, 16/09611-0, 15/20783-5)

CAMPOS, JULIANE C.; BAEHR, LESLIE M.; FERREIRA, NIKOLAS D.; BOZI, LUIZ H. M.; ANDRES, ALLEN M.; RIBEIRO, MARCIO A. C.; GOTTLIEB, ROBERTA A.; BODINE, SUE C.; FERREIRA, JULIO C. B.. beta(2)-adrenoceptor activation improves skeletal muscle autophagy in neurogenic myopathy. FASEB JOURNAL, v. 34, n. 4, FEB 2020. (18/18627-3, 16/01633-5, 17/16540-5, 12/14416-1, 15/50429-9, 17/16694-2)

CAMPOS, JULIANE C.; CHEN, CHE-HONG; FERREIRA, JULIO C. B.. Comment on: "Aldehyde dehydrogenases contribute to skeletal muscle homeostasis in healthy, aging, and Duchenne muscular dystrophy patients" by Etienne et al.. JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE, v. 11, n. 6, p. 2-pg., 2020-07-29. (15/22814-5, 17/16540-5, 19/18444-9, 19/25049-9)

CAMPOS, JULIANE CRUZ; MARCHESI BOZI, LUIZ HENRIQUE; KRUM, BARBARA; GRASSMANN BECHARA, LUIZ ROBERTO; FERREIRA, NIKOLAS DRESCH; ARINI, GABRIEL SANTOS; ALBUQUERQUE, RUDA PRESTES; TRAA, ANNIKA; OGAWA, TAKAFUMI; VAN DER BLIEK, ALEXANDER M.; et al. Exercise preserves physical fitness during aging through AMPK and mitochondrial dynamics. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v. 120, n. 2, p. 11-pg., 2023-01-10. (13/07937-8, 19/18444-9, 17/16540-5, 19/07221-9, 19/25049-9, 15/22814-5, 16/09611-0, 17/16694-2)