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Curr Genet. 2018 Aug;64(4):761-767. doi: 10.1007/s00294-017-0799-z. Epub 2017 Dec 19.

Emerging roles for sphingolipids in cellular aging.

Singh P1,2, Li R3,4.

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Laboratory of Adjuvant and Antigen Research, US Military HIV Research Program, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD, 20910, USA.
US Military HIV Research Program, Henry M. Jackson Foundation for the Advancement of Military Medicine, 6720A Rockledge Drive, Bethesda, MD, 20817, USA.
Department of Cell Biology, Center for Cell Dynamics, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Department of Chemical and Biomolecular Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA.


Aging is a gradual loss of physiological functions as organisms' progress in age. Although aging in multicellular organisms is complex, some fundamental mechanisms and pathways may be shared from the single cellular yeast to human. Budding yeast Saccharomyces cerevisiae has been established model system for aging studies. A yeast cell divides asymmetrically to produce two cells that differ in size and age. The one that is smaller coming from bud is a newborn cell that with a full replicative potential head irrespective of the replicative age of its mother-the larger cell from which the bud grows out before division. The age asymmetry between daughter and mother is thought to be dependent on asymmetric segregation of certain factors such as protein aggregates, extrachromosomal DNA (ERCs) and dysfunctional organelles during successive cell divisions of the yeast replicative lifespan (RLS). It is also thought that certain plasma membrane proteins, in particular multidrug-resistant (MDR) proteins, asymmetrically partition between the mother and the bud based on the age of the polypeptides. Functional decline associated with the molecular aging of those proteins contributes to the fitness decline at advance age. In our recent study, we showed that sphingolipids facilitate the age-dependent segregation of MDRs between daughter and mother cell. In this review, we highlight and discuss the potential mechanisms by which sphingolipids regulate the aging process in yeast and cells of vertebrate animals including human.


Asymmetric cell division; Multidrug resistance proteins; Replicative aging; Sphingolipids

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