Evidence map›Paper›PMID 40993467›Full record

ArticleGeroScience2026

Glucagon receptor signaling is indispensable for the healthspan effects of caloric restriction in aging male mice.

Kassandra R Bruner, Isabella R Byington, Tyler J Marx, Anastasiia Vasileva, Temara Fletcher, Susma Ghimire, India J Zappia, Yashika Shaju, Janan Zeng, Hallie R Wachsmuth and 5 more

Abstract read
In one paragraph

Article in GeroScience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Twelve weeks of voluntary wheel running restores glucagon sensitivity in middle-aged mice.American journal of physiology. Endocrinology and metabolism · 2026
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Kassandra R Bruner *College of Medicine, Department of Medicine, Division of Endocrinology, University of Arizona, Tucson, AZ, USA.
Isabella R Byington *College of Medicine, Department of Medicine, Division of Endocrinology, University of Arizona, Tucson, AZ, USA.
Tyler J MarxCollege of Medicine, Department of Medicine, Division of Endocrinology, University of Arizona, Tucson, AZ, USA.
Anastasiia VasilevaCollege of Medicine, Department of Medicine, Division of Endocrinology, University of Arizona, Tucson, AZ, USA.
Temara FletcherCollege of Medicine, Department of Medicine, Division of Endocrinology, University of Arizona, Tucson, AZ, USA.
Susma GhimireCollege of Medicine, Department of Medicine, Division of Endocrinology, University of Arizona, Tucson, AZ, USA.
India J ZappiaCollege of Medicine, Department of Medicine, Division of Endocrinology, University of Arizona, Tucson, AZ, USA.
Yashika ShajuCollege of Medicine, Department of Medicine, Division of Endocrinology, University of Arizona, Tucson, AZ, USA.
Janan ZengCollege of Medicine, Department of Medicine, Division of Endocrinology, University of Arizona, Tucson, AZ, USA.
Hallie R WachsmuthPhysiological Sciences Graduate Interdisciplinary Program, University of Arizona, Tucson, AZ, USA.
Thadeus W CarlyonCollege of Medicine, Department of Medicine, Division of Endocrinology, University of Arizona, Tucson, AZ, USA.
David G BesselsenUniversity Animal Care, University of Arizona, Tucson, AZ, USA.
Daniel J DruckerLunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, Toronto, Canada.
Frank A DucaDepartment of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, AZ, USA.
Jennifer H SternCollege of Medicine, Department of Medicine, Division of Endocrinology, University of Arizona, Tucson, AZ, USA. jhstern@arizona.edu.ORCID 0000-0002-5336-1358

Funding

Investigating the Role of Hepatic Glucagon Receptor Signaling in Healthspan and AgingR01AG079924 · NIA · UNIVERSITY OF ARIZONA · PI JENNIFER HELENE STERN · 2024 to 2026
$1.4M
Investigations to Assess the Role of Glucagon Signaling in Healthspan and AgingR00AG055649 · NIA · UNIVERSITY OF ARIZONA · PI STERN, JENNIFER HELENE · 2018 to 2022
$860k
Investigating the Role of Hepatic Glucagon Receptor Signaling in Healthspan and AgingR56AG079924 · NIA · UNIVERSITY OF ARIZONA · PI STERN, JENNIFER HELENE · 2024 to 2024
$316k
Arizona Biomedical Research Commission ADHS-RFGA2022-010-04NIA NIH HHS R00 AG055649NIA NIH HHS R00AG055649NIA NIH HHS R01 AG079924NIA NIH HHS R01AG079924NIA NIH HHS R56 AG079924NIA NIH HHS R56AG079924
6 · The paper itself

Abstract

Obesity and type 2 diabetes mellitus accelerate aging, shortening the duration of healthspan. Conversely, chronic calorie restriction (CR) extends healthspan. Research aimed at understanding the mechanism by which CR slows aging has focused heavily on insulin and downstream signaling cascades. Glucagon, a hormone that counter-regulates insulin, is commonly affected by these same interventions. To investigate the role of glucagon in aging, we used dietary manipulation, global and liver-specific glucagon receptor knockout, and pharmacological glucagon receptor activation. We found that globally eliminating glucagon receptor signaling (Gcgr KO) decreases median lifespan by 35% in lean mice. Extending these findings to metabolic health, we found that glucagon receptor signaling is indispensable to the metabolic response to chronic CR in young and aged mice. While CR decreased liver fat, serum triglyceride, and serum cholesterol in WT mice, these metabolic benefits were absent in Gcgr KO mice. In line with these observations, we found that critical nutrient-sensing pathways known to improve aging are dysregulated in mice lacking glucagon receptor signaling at the liver (Gcgr

Indexed as

AgingCaloric RestrictionLongevityReceptors, GlucagonAnimalsGlucagonLiverMaleMiceMice, Inbred C57BLMice, KnockoutSignal TransductionGlucagonReceptors, GlucagonAgingCaloric restrictionGlucagonHealthspan

Identifiers

PMID40993467
PMCPMC12972411

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.