Ageing research reviewsJun 17, 2026

Biomarkers and Treatments Linked to Hutchinson-Gilford Syndrome

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 18, 2026

Abstract

Hutchinson-Gilford progeria syndrome (HGPS) is primarily caused by the LMNA c.1824C>T mutation, leading to the accumulation of progerin.

Progerin accumulation disrupts nuclear structure and DNA organization, resulting in cellular damage and aging-related processes.
Clinical manifestations of HGPS include growth impairment, lipodystrophy, musculoskeletal issues, and severe vascular disease, with cardiovascular events being the main cause of death.
Potential biomarkers for HGPS include molecular markers like progerin levels and telomere shortening, as well as cellular markers related to oxidative stress and inflammation.
Preclinical models, such as progeroid mice and genetically edited minipigs, support the validation of these biomarkers for research and therapeutic purposes.
Therapeutic strategies are evolving beyond farnesyltransferase inhibitors, with treatments like lonafarnib showing improved vascular outcomes but highlighting ongoing challenges in cardiovascular health.
Emerging therapies may benefit from the use of biomarker-guided approaches, integrating multiple biomarkers with combination therapies for precision treatment in HGPS.

Simplified

Hutchinson-Gilford progeria syndrome (HGPS) is an ultra-rare premature aging disorder caused predominantly by a de novo LMNA c.1824C>T mutation that produces progerin, a truncated and permanently farnesylated lamin A isoform. Progerin accumulation disrupts nuclear lamina integrity and chromatin organization, inducing persistent DNA damage responses, telomere attrition, mitochondrial dysfunction, and cellular senescence. These processes drive a multisystem clinical phenotype characterized by growth impairment, lipodystrophy, musculoskeletal abnormalities, and rapidly progressive vascular disease, with cardiovascular events as the leading cause of mortality. Biomarkers could be used in clinical trails and preclinical models for research purposes. Current candidates span four major categories: (i) molecular markers, including LMNA genotype, progerin levels, γH2AX/pATM signaling, telomere shortening, and epigenetic alterations; (ii) cellular markers reflecting oxidative stress, mitochondrial impairment, and senescence-associated secretory phenotype (SASP); (iii) systemic inflammatory and immune mediators; and (iv) vascular structural and functional indices such as arterial stiffness and endothelial dysfunction, which correlate strongly with survival. Preclinical progeroid mouse models and LMNA-edited minipigs have facilitated translational validation of these biomarker axes. Therapeutic approaches now extend beyond farnesyltransferase inhibition. Lonafarnib improves vascular outcomes and survival; however, persistent cardiovascular decline indicates residual unmet need. Emerging interventions-including mTOR modulation, senolytics, anti-inflammatory agents, metabolic support, antisense oligonucleotides, and gene-editing strategies targeting progerin production-may benefit from biomarker-guided implementation. The integration of multi-parameter biomarker panels with mechanism-based combination therapies represents a promising direction toward precision management in HGPS.

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Competing interests

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

PubMed

Biomarkers and Treatments Linked to Hutchinson-Gilford Syndrome

Abstract

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Funding

Competing interests

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