bioRxiv : the preprint server for biologyAug 20, 2026

The longevity-linked enzyme UBE3C controls lamin B1 levels by selective cell recycling and slows aging

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

Updated Aug 21, 2026

Abstract

Ubiquitin E3 ligase UBE3C is strongly associated with exceptional longevity and declines with age across human tissues.

Nuclear lamina integrity is essential for cellular health throughout life and deteriorates as humans age.
Knockdown of UBE3C leads to premature cell aging and destabilizes important nuclear lamina components, Lamin B1 and Lamin B receptor.
A longevity-associated variant of UBE3C appears to delay cellular aging and maintain levels of Lamin B1 and Lamin B receptor.
UBE3C directly interacts with Lamin B1 and Lamin B receptor, influencing their levels through a specific type of cellular recycling process.
The protein CKAP4, which is found in the endoplasmic reticulum, connects UBE3C and Lamin B1, linking the turnover of nuclear lamina to cellular recycling.

Simplified

Nuclear lamina integrity is fundamental to cellular homeostasis across the lifespan ¹ , and its progressive deterioration is closely linked to human aging ² . Yet, the regulatory mechanism that govern this decline and how they might be counteracted in long-lived individuals remain poorly defined. Here, by combining whole-exome sequencing of Ashkenazi Jewish centenarians with GTEx transcriptomes, we identify ubiquitin E3 ligase UBE3C strongly associated with exceptional longevity and progressively declines with age across human tissues. UBE3C knockdown triggers premature senescence and destabilizes key nuclear lamina components Lamin B1 (LMNB1) and Lamin B receptor (LBR), while the longevity-associated UBE3C variant delays senescence and preserves LMNB1/LBR expression. Mechanistically, UBE3C interacts directly with LMNB1/LBR and modulates their abundance via selective autophagy. Notably, we uncover the ER- resident autophagy trigger CKAP4 ³ bridges UBE3C and LMNB1. UBE3C loss enhances LMNB1-CKAP4 binding, linking nuclear lamina turnover to autophagy. Together, our findings establish UBE3C as a central guardian of nuclear lamina maintenance during senescence and offering novel insights into interventions against age-related nuclear lamina deterioration.

Full Text

Full text is available at the source.

View Full Text ↗

Featured in

Longevity & AgingIssue #51

A cancer drug already in clinics may slow aging by quieting a key inflammatory signal

↗

The longevity-linked enzyme UBE3C controls lamin B1 levels by selective cell recycling and slows aging

Abstract

Full Text

Featured in

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week:

Recent issues from the longevity & aging brief