A new research paper was published in Aging (“Aging (Albany NY)” by Medline/PubMed, “Aging-US” by Web of Science) Volume 14, Issue 16, entitled, “Systemic lipolysis promotes physiological fitness in Drosophila melanogaster.”

A large body of literature shows that lipid metabolism exerts profound regulatory effects on aging and affects stress responses. Interventions such as caloric restriction or fasting robustly promote lipid catabolism and improve aging-related phenotypical markers.

Researchers Linshan Shang, Elizabeth Aughey, Huiseon Kim, Timothy D. Heden, Lu Wang, Charles P. Najt, Nicholas Esch, Sophia Brunko, Juan E. Abrahante, Marissa Macchietto, Mara T. Mashek, Todd Fairbanks, Daniel E. L. Promislow, Thomas P. Neufeld, and Douglas G. Mashek from the University of Minnesota and University of Washington investigated the direct effect of increased lipid catabolism via overexpression of bmm (brummer, FBgn0036449), the major triglyceride hydrolase in Drosophila, on lifespan and physiological fitness.

Comprehensive characterization was carried out using RNA-seq, lipidomics and metabolomics analysis. Global overexpression of bmm strongly promoted numerous markers of physiological fitness, including increased female fecundity, fertility maintenance, preserved locomotion activity, increased mitochondrial biogenesis and oxidative metabolism. Since bmm drives fatty acid oxidation, the data in this study implicated differential partitioning of glucose into the pentose phosphate pathway and purine biosynthesis between males and females. However, the underlying mechanisms through which bmm elicits these sex-specific effects remains to be determined.

“Increased bmm robustly upregulated the heat shock protein 70 (Hsp70) family of proteins, which equipped the flies with higher resistance to heat, cold, and ER [endoplasmic reticulum] stress via improved proteostasis.”

Despite improved physiological fitness, bmm overexpression did not extend lifespan. Taken together, these data show that bmm overexpression has broad beneficial effects on physiological fitness, but not lifespan.

“Collectively, these studies reveal diverse beneficial effects of global elevation of lipolysis on physiological fitness. This work provides additional rationale for pursuing therapeutic approaches, as done previously [39], that enhance lipolysis to mitigate metabolic and aging-related diseases.”

DOI: https://doi.org/10.18632/aging.204251

Corresponding Author: Douglas G. Mashek – Email: [email protected]

Keywords: brummer, lipolysis, physiological fitness, stress resistance, proteostasis

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Launched in 2009, Aging (Aging-US) publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

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