Cell Reports (Nov 2024)
Metabolite signatures of chronological age, aging, survival, and longevity
- Paola Sebastiani,
- Stefano Monti,
- Michael S. Lustgarten,
- Zeyuan Song,
- Dylan Ellis,
- Qu Tian,
- Michaela Schwaiger-Haber,
- Ethan Stancliffe,
- Anastasia Leshchyk,
- Meghan I. Short,
- Andres V. Ardisson Korat,
- Anastasia Gurinovich,
- Tanya Karagiannis,
- Mengze Li,
- Hannah J. Lords,
- Qingyan Xiang,
- Megan M. Marron,
- Harold Bae,
- Mary F. Feitosa,
- Mary K. Wojczynski,
- Jeffrey R. O’Connell,
- May E. Montasser,
- Nicole Schupf,
- Konstantin Arbeev,
- Anatoliy Yashin,
- Nicholas Schork,
- Kaare Christensen,
- Stacy L. Andersen,
- Luigi Ferrucci,
- Noa Rappaport,
- Thomas T. Perls,
- Gary J. Patti
Affiliations
- Paola Sebastiani
- Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, MA 02111, USA; Department of Medicine, School of Medicine, Tufts University, Boston, MA 02111, USA; Corresponding author
- Stefano Monti
- Department of Medicine, Chobanian & Avedisian School of Medicine, Boston University, Boston, MA 02118, USA; Bioinformatics Program, Boston University, Boston, MA 02215, USA
- Michael S. Lustgarten
- Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA
- Zeyuan Song
- Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, MA 02111, USA
- Dylan Ellis
- Institute for Systems Biology, Seattle, WA 98109, USA
- Qu Tian
- Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, Baltimore, MD 21224, USA
- Michaela Schwaiger-Haber
- Department of Chemistry, Washington University in St. Louis, St. Louis, MO 63130, USA
- Ethan Stancliffe
- Department of Chemistry, Washington University in St. Louis, St. Louis, MO 63130, USA
- Anastasia Leshchyk
- Bioinformatics Program, Boston University, Boston, MA 02215, USA
- Meghan I. Short
- Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, MA 02111, USA; Department of Medicine, School of Medicine, Tufts University, Boston, MA 02111, USA
- Andres V. Ardisson Korat
- Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA
- Anastasia Gurinovich
- Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, MA 02111, USA; Department of Medicine, School of Medicine, Tufts University, Boston, MA 02111, USA
- Tanya Karagiannis
- Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, MA 02111, USA; Department of Medicine, School of Medicine, Tufts University, Boston, MA 02111, USA
- Mengze Li
- Bioinformatics Program, Boston University, Boston, MA 02215, USA
- Hannah J. Lords
- Bioinformatics Program, Boston University, Boston, MA 02215, USA
- Qingyan Xiang
- Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, MA 02111, USA
- Megan M. Marron
- Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA 15213, USA
- Harold Bae
- Biostatistics Program, College of Health, Oregon State University, Corvallis, OR 97331, USA
- Mary F. Feitosa
- Department of Genetics, Washington University School of Medicine, St. Louis, MO 63130, USA
- Mary K. Wojczynski
- Department of Genetics, Washington University School of Medicine, St. Louis, MO 63130, USA
- Jeffrey R. O’Connell
- Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA
- May E. Montasser
- Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA
- Nicole Schupf
- Department of Epidemiology, Columbia University Medical Center, New York, NY 10032, USA
- Konstantin Arbeev
- Social Science Research Institute, Duke University, Durham, NC 27708, USA
- Anatoliy Yashin
- Social Science Research Institute, Duke University, Durham, NC 27708, USA
- Nicholas Schork
- The Translational Genomics Research Institute, Phoenix, AZ 85004, USA
- Kaare Christensen
- Danish Aging Research Center, University of Southern Denmark, 5000 Odense, Denmark
- Stacy L. Andersen
- Department of Medicine, Chobanian & Avedisian School of Medicine, Boston University, Boston, MA 02118, USA
- Luigi Ferrucci
- Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, Baltimore, MD 21224, USA
- Noa Rappaport
- Institute for Systems Biology, Seattle, WA 98109, USA
- Thomas T. Perls
- Department of Medicine, Chobanian & Avedisian School of Medicine, Boston University, Boston, MA 02118, USA
- Gary J. Patti
- Department of Chemistry, Washington University in St. Louis, St. Louis, MO 63130, USA
- Journal volume & issue
-
Vol. 43,
no. 11
p. 114913
Abstract
Summary: Metabolites that mark aging are not fully known. We analyze 408 plasma metabolites in Long Life Family Study participants to characterize markers of age, aging, extreme longevity, and mortality. We identify 308 metabolites associated with age, 258 metabolites that change over time, 230 metabolites associated with extreme longevity, and 152 metabolites associated with mortality risk. We replicate many associations in independent studies. By summarizing the results into 19 signatures, we differentiate between metabolites that may mark aging-associated compensatory mechanisms from metabolites that mark cumulative damage of aging and from metabolites that characterize extreme longevity. We generate and validate a metabolomic clock that predicts biological age. Network analysis of the age-associated metabolites reveals a critical role of essential fatty acids to connect lipids with other metabolic processes. These results characterize many metabolites involved in aging and point to nutrition as a source of intervention for healthy aging therapeutics.
