Endogenous mitochondrial NAD(P)H fluorescence can predict lifespan.

Autor: Morrow CS; Department of Molecular Metabolism, Harvard TH Chan School of Public Health, Boston, MA, USA., Yao P; Department of Molecular Metabolism, Harvard TH Chan School of Public Health, Boston, MA, USA., Vergani-Junior CA; Department of Molecular Metabolism, Harvard TH Chan School of Public Health, Boston, MA, USA.; Department of Biochemistry and Tissue Biology, University of Campinas, Campinas, SP, Brazil., Anekal PV; MicRoN Core, Harvard Medical School, Boston, MA, USA., Montero Llopis P; MicRoN Core, Harvard Medical School, Boston, MA, USA., Miller JW; Department of Biostatistics, Harvard University, Boston, MA, USA., Benayoun BA; Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.; Molecular and Computational Biology Department, USC Dornsife College of Letters, Arts and Sciences, Los Angeles, CA, USA.; Biochemistry and Molecular Medicine Department, USC Keck School of Medicine, Los Angeles, CA, USA., Mair WB; Department of Molecular Metabolism, Harvard TH Chan School of Public Health, Boston, MA, USA. wmair@hsph.harvard.edu.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2024 Nov 21; Vol. 7 (1), pp. 1551. Date of Electronic Publication: 2024 Nov 21.
DOI: 10.1038/s42003-024-07243-w
Abstrakt: Many aging clocks have recently been developed to predict health outcomes and deconvolve heterogeneity in aging. However, existing clocks are limited by technical constraints, such as low spatial resolution, long processing time, sample destruction, and a bias towards specific aging phenotypes. Therefore, here we present a non-destructive, label-free and subcellular resolution approach for quantifying aging through optically resolving age-dependent changes to the biophysical properties of NAD(P)H in mitochondria through fluorescence lifetime imaging (FLIM) of endogenous NAD(P)H fluorescence. We uncover age-dependent changes to mitochondrial NAD(P)H across tissues in C. elegans that are associated with a decline in physiological function and construct non-destructive, label-free and cellular resolution models for prediction of age, which we refer to as "mito-NAD(P)H age clocks." Mito-NAD(P)H age clocks can resolve heterogeneity in the rate of aging across individuals and predict remaining lifespan. Moreover, we spatiotemporally resolve age-dependent changes to mitochondria across and within tissues, revealing multiple modes of asynchrony in aging and show that longevity is associated with a ubiquitous attenuation of these changes. Our data present a high-resolution view of mitochondrial NAD(P)H across aging, providing insights that broaden our understanding of how mitochondria change during aging and approaches which expand the toolkit to quantify aging.
Competing Interests: Competing interests: The authors declare no competing interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
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