Peptide C43-4 extends yeast lifespan via APCCdh1 in quiescent cells
In this abstract, a yeast two-hybrid screen found peptides binding the APC subunit Apc10; only C43-4 increased chronological lifespan of nondividing yeast, required the Cdh1 co-activator, and also extended C. elegans lifespan. [1]
Automatic summary · not editorially reviewed
The key findings
The source at a glance
- Study type / format
- Abstract of a preclinical laboratory study.
- Population / context
- Yeast cells (dividing and quiescent) and C. elegans.
- Summary based on
- Study abstract
- Original publication
- September 16, 2026
Proposed APC activation in quiescent yeast
The authors note that senescence, an irreversible nondividing state, is a conserved aging hallmark. They previously reported that yeast Anaphase Promoting Complex (APC) mutants shorten lifespan of dividing and nondividing cells. Here they propose that activating the APC would help maintain quiescent yeast cells and thereby delay senescence and aging. They observed that APC activity in aging quiescent cells becomes increasingly impaired: the APC substrates Clb1 and Mps1 accumulated in aging cells reintroduced back into the cell cycle.
Supporting source [1]
C43-4 and Cdh1-dependent chronological lifespan
A yeast two-hybrid screen recovered peptides interacting with Apc10. Peptides were tested on replicative lifespan (RLS) of dividing cells and chronological lifespan (CLS) of nondividing cells. Several peptides increased RLS of wild-type cells, but only C43-4 increased CLS, which required the APC Cdh1 co-activator but not the Cdc20 co-activator. In cells expressing C43-4, Clb1 and Mps1 stayed low when aging quiescent cells were reintroduced into the cell cycle. Synthetic C43-4 added to aging quiescent cells increased CLS even when added at late aging stages. APC subunit and co-activator mutations blocked this CLS extension.
Supporting source [1]
Htz1 homology, mutant loss and C. elegans lifespan
Htz1, which shares sequence homology with C43-4, suppressed APC mutant phenotypes and stabilized Apc10. The authors individually mutated the 6 amino acids C43-4 shares with Htz1; one mutant disrupted the C43-4–Apc10 two-hybrid interaction and abolished the C43-4-dependent CLS increase. C43-4 action is described as evolutionarily conserved, as C43-4 increased C. elegans lifespan in a daf-16- and aak-2-dependent manner. The authors call C43-4 the first peptide of its kind to specifically activate the anti-aging APCCdh1 complex.
Supporting source [1]
How to interpret this
This is an abstract; the full text was not reviewed. Results come from yeast and C. elegans experiments, not human lifespan studies. The APC activation is a proposal, and C43-4 is an experimental peptide, not a validated or approved product.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
Harris RE, Postnikoff SD, Shukla NK, Harkness AH, Brooks HM, Khawaja AA, Malo ME, Zapien-Verdugo C, Waddell BM, Wu CW, Harkness TAA. · europepmc.org · September 16, 2026