Human-Relevant Ptpn6 Mutation Reveals Complex Links Between Immunity, Metabolism and Liver Aging

BUFFALO, NY — September 16, 2026 — A new #research paper was #published in Volume 18 of Aging on August 28, 2026, titled “Human-relevant Ptpn6 mutation alters immune and hepatic functions during aging.”

The study examines how a mutation affecting the immune and metabolic regulator SHP-1 reshapes liver function during aging, revealing that improved glucose metabolism can coexist with immune-cell accumulation and liver fibrosis.

The research was led by first author Beisy Laborit Labrada from the Institut Universitaire de Cardiologie et de Pneumologie de Québec (CRIUCPQ), Université Laval, Québec, Canada. André Marette, from CRIUCPQ and the Department of Medicine at Université Laval, is the corresponding author.

SHP-1, encoded by the PTPN6 gene, is a protein tyrosine phosphatase that helps regulate both immune responses and metabolic signaling. In immune cells, it generally restrains signaling pathways that control cellular activation, while in metabolic tissues it acts as a negative regulator of insulin signaling. This dual function places SHP-1 at an important intersection between immunity and metabolism, two systems that undergo substantial changes during aging.

The study centered on a rare PTPN6Ala455Thr variant originally identified in a French-Canadian family with early-onset severe emphysema. The human mutation moderately reduces SHP-1 phosphatase activity. To investigate its longer-term effects, the researchers used mice carrying the corresponding Ptpn6Ala457Thr mutation and compared young adult mice at 5.6 months with older animals at 16–19 months. Unlike more severe SHP-1-deficient mouse models, these animals have lifespans comparable to wild-type mice, allowing the consequences of partial SHP-1 dysfunction to be examined across aging.

Full press release - https://www.aging-us.com/news-room/human-relevant-ptpn6-mutation-reveals-complex-links-between-immunity-metabolism-and-liver-aging

DOI - https://doi.org/10.18632/aging.206413

Corresponding author - André Marette - andre.marette@criucpq.ulaval.ca

Abstract video - https://www.youtube.com/watch?v=lyn__UY9Buk

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