Age- and diet-associated metabolome remodeling characterizes the aging process driven by damage accumulation.
Aging is thought to be associated with increased molecular damage, but representative markers vary across conditions and organisms, making it difficult to assess properties of cumulative damage throughout lifespan. We used nontargeted metabolite profiling to follow age-associated trajectories of >15,000 metabolites in Drosophila subjected to control and lifespan-extending diets. We find that aging is associated with increased metabolite diversity and low-abundance molecules, suggesting they include cumulative damage. Remarkably, the number of detected compounds leveled-off in late-life, and this pattern associated with survivorship. Fourteen percent of metabolites showed age-associated changes, which decelerated in late-life and long-lived flies. In contrast, known metabolites changed in abundance similarly to nontargeted metabolites and transcripts, but did not increase in diversity. Targeted profiling also revealed slower metabolism and accumulation of lifespan-limiting molecules. Thus, aging is characterized by gradual metabolome remodeling, and condition- and advanced age-associated deceleration of this remodeling is linked to mortality and molecular damage.DOI: http://dx.doi.org/10.7554/eLife.02077.001.
Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, United States.
Andrei S
AS
Avanesov
Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, United States.
Siming
S
Ma
Broad Institute, Cambridge, United States.
Kerry A
KA
Pierce
Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, United States.
Sun Hee
SH
Yim
Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, United States.
Byung Cheon
BC
Lee
Broad Institute, Cambridge, United States.
Clary B
CB
Clish
Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, United States Broad Institute, Cambridge, United States vgladyshev@rics.bwh.harvard.edu.
Vadim N
VN
Gladyshev
D000375:Aging / Q000378:metabolism*; D000818:Animals; D004032:Diet; D004330:Drosophila / Q000378:metabolism / Q000502:physiology*; D020869:Gene Expression Profiling; D008136:Longevity; D055442:Metabolome; D012333:RNA, Messenger / Q000235:genetics
D012333:RNA, Messenger
aging; damage; lifespan; metabolite profiling