Related Experiment Video
Updated: Jan 14, 2026

A Suppressor Screen for the Characterization of Genetic Links Regulating Chronological Lifespan in Saccharomyces cerevisiae
Published on: September 17, 2020
The protein phosphatase 6 subunit SAPS3 modulates lifespan by regulating metabolism
Ying Yang1, Da Eun Kang1, Qi Fan1
1Department of Molecular Biology and Biochemistry, Charlie Dunlop School of Biological Sciences, University of California, Irvine, Irvine, CA 92697, USA.
None:
Aging is characterized by disruptions in metabolic homeostasis, yet the mechanisms that regulate these metabolic changes remain poorly understood. We show that the serine/threonine-protein phosphatase 6 (PP6) regulatory subunit 3, SAPS3, is a critical regulator of metabolism during aging. SAPS3 deletion significantly extends lifespan in mice and counteracts age-related impairments in metabolic health. SAPS3 deficiency improves the effects of aging on the affective behaviors, cognition, and motor functions in aged mice. We find that SAPS3 expression is increased during aging to inhibit adenosine monophosphate-activated kinase (AMPK) activity. Deletion of SAPS3 leads to AMPK activation and reverses cellular senescence and aging-induced metabolic alterations. Using in vivo U-13C6-D-glucose tracing and metabolomic analysis, we find that SAPS3 deficiency restores metabolic homeostasis with increased glycolysis, tricarboxylic acid (TCA) cycle, and decreased fatty acid synthesis in aged mice. These findings highlight a critical role of the SAPS3/PP6 phosphatase complex in aging and suggest that strategies targeting SAPS3 may promote longevity and healthy aging.
Related Concept Videos
PI3K/mTOR/AKT Signaling Pathway
The JAK-STAT Signaling Pathway
Regulated Protein Degradation
Regulated Protein Degradation
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Protein Kinases and Phosphatases
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Covalently Linked Protein Regulators
These groups modify specific amino acids in a protein....

