Nature communicationsDec 13, 2025

ARMH4 may speed up aging by keeping a self-reinforcing growth signal active

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 27, 2026

Abstract

Essence

appears to promote aging by sustaining growth-factor signaling that increases protein synthesis and suppresses autophagy.

Evidence

A whole-body Armh4- study found lower spontaneous mortality, extended maximum lifespan, delayed female sexual maturity by one week, reduced age-related pathology in several organs, and mechanistic links between ARMH4, IGF1R/FGFR1, PI3K-Akt-mTORC1, Ras-MEK-ERK, and c-Myc signaling.

Caveat

The causal aging evidence is from a mouse knockout model, and the abstract does not show whether ARMH4 inhibition is feasible, safe, or similarly anti-aging in humans.

Simplified

Aging is an inevitable process integrating chronological alterations of multiple organs. A growing aging population necessitates feasible anti-aging strategies to deal with age-associated health problems. We previously performed a proteomics analysis in a healthy-aging cohort, and revealed an age-related downregulation of . Here we generate a whole-body Armh4- line, and investigate its impact on systemic aging. Under normal feeding conditions, Armh4 deficiency significantly lowers spontaneous mortality and extends maximum lifespan. In the female mice, Armh4 deficiency postpones sexual maturity for one week. At the organ level, the age-related pathologies of the heart, liver, kidney, and spleen are substantially alleviated by Armh4 deletion. Mechanistically, ARMH4 interacts with IGF1R/FGFR1 to sensitize the activation of PI3K-Akt-mTORC1 and Ras-MEK-ERK pathways, consequently promoting protein synthesis and inhibiting autophagy. Moreover, ARMH4 is required for the maintenance of IGF1R/FGFR1 expressions through regulating the transcription factor c-Myc. Therefore, ARMH4 maintains a positive-feedback growth signaling to promote aging.

Key numbers

25 months

Lifespan Extension

Maximum lifespan of knockout mice under natural feeding conditions.

1 week

Delayed Sexual Maturity

Comparison of sexual maturity timing in knockout vs. wild-type female mice.

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Funding

Competing interests

0%of authors

0 of 13

authors report competing interests

13 report none

PubMed

ARMH4 may speed up aging by keeping a self-reinforcing growth signal active

Abstract

Key numbers

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Funding

Competing interests

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