Lifespan-extending interventions enhance lipid-supported mitochondrial respiration inCaenorhabditis elegans

Autor(es)

Macedo, Felipe ^[1] ; Romanatto, Talita ^[2] ; de Assis, Carolina Gomes ^[1] ; Buis, Alexia ^[3] ; Kowaltowski, Alicia J. ^[2] ; Aguilaniu, Hugo ^{[4, 3, 5]} ; da Cunha, Fernanda Marques ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Dept Bioquim, Escola Paulista Med, Rua 3 Maio 100, BR-04044020 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Inst Quim, Dept Bioquim, Sao Paulo - Brazil

^[3] Inst Genom Fonct Lyon, Lyon - France

^[4] CNRS, Paris - France

^[5] Inst Serrapilheira, Rua Dias Ferreira, 78 S202, BR-22431050 Rio De Janeiro, RJ - Brazil

• Tipo de documento: Artigo Científico
• Fonte: FASEB JOURNAL; v. 34, n. 8 JUL 2020.
• Citações Web of Science: 0

Resumo

Dietary restriction and reduced reproduction have been linked to long lifespans in the vast majority of species tested. Although decreased mitochondrial mass and/or function are hallmarks of aging, little is known about the mechanisms by which these organelles contribute to physiological aging or to the effects of lifespan-extending interventions, particularly with respect to oxidative phosphorylation and energy production. Here, we employed the nematodeCaenorhabditis elegansto examine the effects of inhibition of germline proliferation and dietary restriction, both of which extend the lifespan ofC. elegans, on mitochondrial respiratory activity in whole animals and isolated organelles. We found that oxygen consumption rates and mitochondrial mass were reduced in wild-type (WT)C. eleganssubjected to bacterial deprivation (BD) compared with animals fed ad libitum (AL). In contrast, BD decreased the rate of oxygen uptake but not mitochondrial mass in germline-lessglp-1(e2144ts)mutants. Interestingly, mitochondria isolated from animals subjected to BD and/or inhibition of germline proliferation showed no differences in complex I-mediated respiratory activity compared to control mitochondria, whereas both interventions enhanced the efficiency with which mitochondria utilized lipids as respiratory substrates. Notably, the combination of BD and inhibition of germline proliferation further increased mitochondrial lipid oxidation compared to either intervention alone. We also detected a striking correlation between lifespan extension in response to BD and/or inhibition of germline proliferation and the capacity ofC. elegansto generate ATP from lipids. Our results thus suggest that the ability to oxidize lipids may be determinant in enhanced longevity. (AU)

• Processo FAPESP: 13/07937-8 - Redoxoma
• Beneficiário: Ohara Augusto
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 15/15526-3 - Estudo do envolvimento da atividade mitocondrial na super-resposta à restrição calórica em Caenorhabditis elegans mutantes para lipl-5
• Beneficiário: Fernanda Marques da Cunha
• Modalidade de apoio: Auxílio à Pesquisa - Regular