A conserved complex lipid signature marks human muscle aging and responds to short-term exercise.
Journal
Nature aging
ISSN: 2662-8465
Titre abrégé: Nat Aging
Pays: United States
ID NLM: 101773306
Informations de publication
Date de publication:
12 Apr 2024
12 Apr 2024
Historique:
received:
23
12
2022
accepted:
22
02
2024
medline:
13
4
2024
pubmed:
13
4
2024
entrez:
12
4
2024
Statut:
aheadofprint
Résumé
Studies in preclinical models suggest that complex lipids, such as phospholipids, play a role in the regulation of longevity. However, identification of universally conserved complex lipid changes that occur during aging, and how these respond to interventions, is lacking. Here, to comprehensively map how complex lipids change during aging, we profiled ten tissues in young versus aged mice using a lipidomics platform. Strikingly, from >1,200 unique lipids, we found a tissue-wide accumulation of bis(monoacylglycero)phosphate (BMP) during mouse aging. To investigate translational value, we assessed muscle tissue of young and older people, and found a similar marked BMP accumulation in the human aging lipidome. Furthermore, we found that a healthy-aging intervention consisting of moderate-to-vigorous exercise was able to lower BMP levels in postmenopausal female research participants. Our work implicates complex lipid biology as central to aging, identifying a conserved aging lipid signature of BMP accumulation that is modifiable upon a short-term healthy-aging intervention.
Identifiants
pubmed: 38609524
doi: 10.1038/s43587-024-00595-2
pii: 10.1038/s43587-024-00595-2
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : ZonMw (Netherlands Organisation for Health Research and Development)
ID : 91715305
Organisme : Velux Fonden (Velux Foundation)
ID : 1063
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.
Références
Libby, P. et al. Atherosclerosis. Nat. Rev. Dis. Prim. 5, 1–18 (2019).
Knottnerus, S. J. G. et al. Disorders of mitochondrial long-chain fatty acid oxidation and the carnitine shuttle. Rev. Endocr. Metab. Disord. 19, 93–106 (2018).
pubmed: 29926323
pmcid: 6208583
doi: 10.1007/s11154-018-9448-1
Gao, A. W. et al. A sensitive mass spectrometry platform identifies metabolic changes of life history traits in C. elegans. Sci. Rep. 7, 2408 (2017).
pubmed: 28546536
pmcid: 5445081
doi: 10.1038/s41598-017-02539-w
Houtkooper, R. H. et al. The metabolic footprint of aging in mice. Sci. Rep. 1, 134 (2011).
pubmed: 22355651
pmcid: 3216615
doi: 10.1038/srep00134
Fahy, E., Cotter, D., Sud, M. & Subramaniam, S. Lipid classification, structures and tools. Biochim. Biophys. Acta 1811, 637–647 (2011).
pubmed: 21704189
pmcid: 3995129
doi: 10.1016/j.bbalip.2011.06.009
Vaz, F. M., Pras-Raves, M., Bootsma, A. H. & van Kampen, A. H. C. Principles and practice of lipidomics. J. Inherit. Metab. Dis. 38, 41–52 (2015).
pubmed: 25409862
doi: 10.1007/s10545-014-9792-6
Wortmann, S. B. et al. Mutations in the phospholipid remodeling gene SERAC1 impair mitochondrial function and intracellular cholesterol trafficking and cause dystonia and deafness. Nat. Genet. 44, 797–802 (2012).
pubmed: 22683713
doi: 10.1038/ng.2325
Vreken, P. et al. Defective remodeling of cardiolipin and phosphatidylglycerol in Barth syndrome. Biochem. Biophys. Res. Commun. 279, 378–382 (2000).
pubmed: 11118295
doi: 10.1006/bbrc.2000.3952
Vaz, F. M. et al. Mutations in PCYT2 disrupt etherlipid biosynthesis and cause a complex hereditary spastic paraplegia. Brain 142, 3382–3397 (2019).
pubmed: 31637422
pmcid: 6821184
doi: 10.1093/brain/awz291
Ferdinandusse, S. et al. An autosomal dominant neurological disorder caused by de novo variants in FAR1 resulting in uncontrolled synthesis of ether lipids. Genet. Med. 23, 740–750 (2021).
pubmed: 33239752
doi: 10.1038/s41436-020-01027-3
Sustarsic, E. G. et al. Cardiolipin synthesis in brown and beige fat mitochondria is essential for systemic energy homeostasis. Cell Metab. 28, 159–174 (2018).
pubmed: 29861389
pmcid: 6038052
doi: 10.1016/j.cmet.2018.05.003
Lynes, M. D. et al. Cold-activated lipid dynamics in adipose tissue highlights a role for cardiolipin in thermogenic metabolism. Cell Rep. 24, 781–790 (2018).
pubmed: 30021173
pmcid: 6117118
doi: 10.1016/j.celrep.2018.06.073
Jha, P. et al. Systems analyses reveal physiological roles and genetic regulators of liver lipid species. Cell Syst. 6, 722–733 (2018).
pubmed: 29909277
pmcid: 6054463
doi: 10.1016/j.cels.2018.05.016
Ferrara, P. J. et al. Lysophospholipid acylation modulates plasma membrane lipid organization and insulin sensitivity in skeletal muscle. J. Clin. Invest. 3, e135963 (2021).
Held, N. M. et al. Skeletal muscle in healthy humans exhibits a day-night rhythm in lipid metabolism. Mol. Metab. 37, 100989 (2020).
pubmed: 32272236
pmcid: 7217992
doi: 10.1016/j.molmet.2020.100989
López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M. & Kroemer, G. The hallmarks of aging. Cell 153, 1194–1217 (2013).
pubmed: 23746838
pmcid: 3836174
doi: 10.1016/j.cell.2013.05.039
Johnson, A. A. & Stolzing, A. The role of lipid metabolism in aging, lifespan regulation, and age-related disease. Aging Cell 18, e13048 (2019).
pubmed: 31560163
pmcid: 6826135
doi: 10.1111/acel.13048
Wang, M. C., O’Rourke, E. J. & Ruvkun, G. Fat metabolism links germline stem cells and longevity in C. elegans. Science 322, 957–960 (2008).
pubmed: 18988854
pmcid: 2760269
doi: 10.1126/science.1162011
Seah, N. E. et al. Autophagy-mediated longevity is modulated by lipoprotein biogenesis. Autophagy 12, 261–272 (2016).
pubmed: 26671266
doi: 10.1080/15548627.2015.1127464
Bozek, K. et al. Lipidome determinants of maximal lifespan in mammals. Sci. Rep. 7, 5 (2017).
pubmed: 28127055
pmcid: 5428381
doi: 10.1038/s41598-017-00037-7
Akgoc, Z. et al. Bis(monoacylglycero)phosphate: a secondary storage lipid in the gangliosidoses. J. Lipid Res. 56, 1006–1013 (2015).
pubmed: 25795792
pmcid: 4409277
doi: 10.1194/jlr.M057851
Thornburg, T., Miller, C., Thuren, T., King, L. & Waite, M. Glycerol reorientation during the conversion of phosphatidylglycerol to bis(monoacylglycerol)phosphate in macrophage-like RAW 264.7 cells. J. Biol. Chem. 266, 6834–6840 (1991).
Brotherus, J., Renkonen, O., Herrmann, J. & Fischer, W. Novel stereoconfiguration in lyso-bis-phosphatidic acid of cultured BHK-cells. Chem. Phys. Lipids 13, 178–182 (1974).
pubmed: 4473276
doi: 10.1016/0009-3084(74)90034-6
Showalter, M. R. et al. The emerging and diverse roles of bis(monoacylglycero) phosphate lipids in cellular physiology and disease. Int. J. Mol. Sci. 21, 8067 (2020).
Medoh, U. N. et al. The Batten disease gene product CLN5 is the lysosomal bis(monoacylglycero)phosphate synthase. Science 381, 1182–1189 (2023).
pubmed: 37708259
doi: 10.1126/science.adg9288
Herzog, K. et al. Lipidomic analysis of fibroblasts from Zellweger spectrum disorder patients identifies disease-specific phospholipid ratios. J. Lipid Res. 57, 1447–1454 (2016).
pubmed: 27284103
pmcid: 4959860
doi: 10.1194/jlr.M067470
Chen, J. et al. Lysosomal phospholipase A2 contributes to the biosynthesis of the atypical late endosome lipid bis(monoacylglycero)phosphate. Commun. Biol. 6, 2–10 (2023).
pubmed: 36596993
pmcid: 9810597
doi: 10.1038/s42003-023-04573-z
Held, N. M. et al. Aging selectively dampens oscillation of lipid abundance in white and brown adipose tissue. Sci. Rep. 11, 5932 (2021).
pubmed: 33723320
pmcid: 7961067
doi: 10.1038/s41598-021-85455-4
Grevendonk, L. et al. Impact of aging and exercise on skeletal muscle mitochondrial capacity, energy metabolism, and physical function. Nat. Commun. 12, 4773 (2021).
Remie, C. M. E. et al. Sitting less elicits metabolic responses similar to exercise and enhances insulin sensitivity in postmenopausal women. Diabetologia 64, 2817–2828 (2021).
pubmed: 34510226
pmcid: 8435176
doi: 10.1007/s00125-021-05558-5
Grabner, G. F. et al. Metabolic regulation of the lysosomal cofactor bis(monoacylglycero)phosphate in mice. J. Lipid Res. 61, 995–1003 (2020).
pubmed: 32350080
pmcid: 7328040
doi: 10.1194/jlr.RA119000516
Rampanelli, E. et al. Metabolic injury-induced NLRP3 inflammasome activation dampens phospholipid degradation. Sci. Rep. 7, 2861 (2017).
pubmed: 28588189
pmcid: 5460122
doi: 10.1038/s41598-017-01994-9
Luquain-Costaz, C. et al. Bis(monoacylglycero)phosphate accumulation in macrophages induces intracellular cholesterol redistribution, attenuates liver-X receptor/ATP-binding cassette transporter A1/ATP-binding cassette transporter G1 pathway, and impairs cholesterol efflux. Arterioscler. Thromb. Vasc. Biol. 33, 1803–1811 (2013).
pubmed: 23788762
pmcid: 3989212
doi: 10.1161/ATVBAHA.113.301857
Hullin-Matsuda, F., Luquain-Costaz, C., Bouvier, J. & Delton-Vandenbroucke, I. Bis(monoacylglycero)phosphate, a peculiar phospholipid to control the fate of cholesterol: implications in pathology. Prostaglandins Leukot. Essent. Fatty Acids 81, 313–324 (2009).
Meikle, P. J. et al. Effect of lysosomal storage on bis(monoacylglycero)phosphate. Biochem. J. 411, 71–78 (2008).
pubmed: 18052935
doi: 10.1042/BJ20071043
Schuurman, A. R. et al. The platelet lipidome is altered in patients with COVID-19 and correlates with platelet reactivity. Thromb. Haemost. 122, 1683–1692 (2022).
pubmed: 35850149
pmcid: 9512584
doi: 10.1055/s-0042-1749438
Falabella, M., Vernon, H. J., Hanna, M. G., Claypool, S. M. & Pitceathly, R. D. S. Cardiolipin, mitochondria, and neurological disease. Trends Endocrinol. Metab. 32, 224–237 (2021).
pubmed: 33640250
pmcid: 8277580
doi: 10.1016/j.tem.2021.01.006
Liu, D., Aziz, N. A., Pehlivan, G. & Breteler, M. M. B. Lipidomic correlates of epigenetic aging across the adult lifespan: a population-based study. GeroScience https://doi.org/10.1007/s11357-022-00714-0 (2023).
Cedillo, L. et al. Ether lipid biosynthesis promotes lifespan extension and enables diverse pro-longevity paradigms in Caenorhabditis elegans. eLife 12, e82210 (2023).
Baars, A. et al. Sex differences in lipid metabolism are affected by presence of the gut microbiota. Sci. Rep. 8, 13426 (2018).
pubmed: 30194317
pmcid: 6128923
doi: 10.1038/s41598-018-31695-w
González-Granillo, M. et al. Sex-specific lipid molecular signatures in obesity-associated metabolic dysfunctions revealed by lipidomic characterization in ob/ob mouse. Biol. Sex Differ. 10, 11 (2019).
pubmed: 30808418
pmcid: 6390380
doi: 10.1186/s13293-019-0225-y
Holcomb, L. E., Rowe, P., O’Neill, C. C., DeWitt, E. A. & Kolwicz, S. C. Sex differences in endurance exercise capacity and skeletal muscle lipid metabolism in mice. Physiol. Rep. 10, (2022).
Mouchiroud, L. et al. The NAD+/sirtuin pathway modulates longevity through activation of mitochondrial UPR and FOXO signaling. Cell 154, 430–441 (2013).
pubmed: 23870130
pmcid: 3753670
doi: 10.1016/j.cell.2013.06.016
Smith, P. K. et al. Measurement of protein using bicinchoninic acid. Anal. Biochem. 150, 76–85 (1985).
pubmed: 3843705
doi: 10.1016/0003-2697(85)90442-7
Chambers, M. C. et al. A cross-platform toolkit for mass spectrometry and proteomics. Nat. Biotechnol. 30, 918–920 (2012).
pubmed: 23051804
pmcid: 3471674
doi: 10.1038/nbt.2377
R Core Team. A language and environment for statistical computing. R Foundation for Statistical Computing https://www.r-project.org/ (2019).
Smith, C. A., Want, E. J., O’Maille, G., Abagyan, R. & Siuzdak, G. XCMS: processing mass spectrometry data for metabolite profiling using nonlinear peak alignment, matching, and identification. Anal. Chem. 78, 779–787 (2006).
Ruiz, M. et al. Lipidomics unveils lipid dyshomeostasis and low circulating plasmalogens as biomarkers in a monogenic mitochondrial disorder. JCI Insight 4, e123231 (2019).
pubmed: 31341105
pmcid: 6675547
doi: 10.1172/jci.insight.123231
Huffnagel, I. C. et al. Disease progression in women with X-linked adrenoleukodystrophy is slow. Orphanet J. Rare Dis. https://doi.org/10.1186/s13023-019-1008-6 (2019).
doi: 10.1186/s13023-019-1008-6
pubmed: 31521182
pmcid: 6744701
Bergström, J. Muscle electrolytes in man determined by neutron activation analysis on needle biopsy specimens. Scand. J. Clin. Lab. Invest. 14, 7–110 (1962).
Molenaars, M. et al. Metabolomics and lipidomics in C. elegans using a single sample preparation. Dis. Model. Mech. https://doi.org/10.1242/dmm.047746 (2021).
doi: 10.1242/dmm.047746
pubmed: 33653825
pmcid: 8106956
Gentleman, R. C. et al. Bioconductor: open software development for computational biology and bioinformatics. Genome Biol. 5, R80 (2004).
pubmed: 15461798
pmcid: 545600
doi: 10.1186/gb-2004-5-10-r80
Rohart, F., Gautier, B., Singh, A. & Lê Cao, K. A. mixOmics: an R package for ‘omics feature selection and multiple data integration. PLoS Comput. Biol. 13, e1005752 (2017).
Wickham, H. Ggplot2. Wiley Interdiscip. Rev. Comput. Stat. 3, 180–185 (2011).
doi: 10.1002/wics.147
Ritchie, M. E. et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43, e47 (2015).
pubmed: 25605792
pmcid: 4402510
doi: 10.1093/nar/gkv007
Law, C. W., Chen, Y., Shi, W. & Smyth, G. K. voom: precision weights unlock linear model analysis tools for RNA-seq read counts. Genome Biol. 15, R29 (2014).
pubmed: 24485249
pmcid: 4053721
doi: 10.1186/gb-2014-15-2-r29