Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disease caused by nuclear envelope alterations that lead to accelerated aging and premature death. Several studies have linked health and longevity to cell-extrinsic mechanisms, highlighting the relevance of circulating factors in the aging process as well as in age-related diseases. We performed a global plasma proteomic analysis in two preclinical progeroid models (LmnaG609G/G609G and Zmpste24-/- mice) using aptamer-based proteomic technology. Pathways related to the extracellular matrix, growth factor response and calcium ion binding were among the most enriched in the proteomic signature of progeroid samples compared to controls. Despite the global downregulation trend found in the plasma proteome of progeroid mice, several proteins associated with cardiovascular disease, the main cause of death in HGPS, were upregulated. We also developed a chronological age predictor using plasma proteome data from a cohort of healthy mice (aged 1-30 months), that reported an age acceleration when applied to progeroid mice, indicating that these mice exhibit an "old" plasma proteomic signature. Furthermore, when compared to naturally-aged mice, a great proportion of differentially expressed circulating proteins in progeroid mice were specific to premature aging, highlighting secretome-associated differences between physiological and accelerated aging. This is the first large-scale profiling of the plasma proteome in progeroid mice, which provides an extensive list of candidate circulating plasma proteins as potential biomarkers and/or therapeutic targets for further exploration and hypothesis generation in the context of both physiological and premature aging.

Diego Quintana‐Torres

Alejandra Valle‐Cao

Pablo Bousquets‐Muñoz

Sandra Freitas‐Rodríguez

Francisco Rodríguez

Alejandro Lucia

Carlos López‐Otín

Alejandro López‐Soto

Alicia R. Folgueras

Aging Cell

AGING CELL 的目标是发表最高质量的创新研究，解决衰老生物学的基本问题。为了在 AGING CELL 上发表，这项工作必须为理解老龄化提供重大的新贡献，并引起社区的普遍兴趣。 AGING CELL 力求涵盖老年科学的所有领域，突出揭示衰老过程的机制方面的研究，以及衰老与年龄相关疾病之间的联系。

Aging Cell aims to publish high-quality innovative research that addresses fundamental issues in the biology of aging. To be published in Aging Cell, the work must provide significant new contributions to the understanding of aging and garner broad interest within the community. Aging Cell seeks to cover all areas of geroscience, with a particular emphasis on research that reveals the mechanisms of the aging process and the connections between aging and age-related diseases.

《Aging Cell》旨在发表高质量的创新研究，解决衰老生物学中的基本问题。为了在《Aging Cell》上发表，研究必须为理解老龄化提供重要的新贡献，并引起学术界的广泛关注。《Aging Cell》力求涵盖老年科学的各个领域，特别强调揭示衰老过程机制的研究，以及衰老与年龄相关疾病之间的关系。

The secretome atlas of two mouse models of progeria

This is the first large‐scale profiling of the plasma proteome in progeroid mice, which provides an extensive list of candidate circulating plasma proteins as potential biomarkers and/or therapeutic targets for further exploration and hypothesis generation in the context of both physiological and premature aging.

Category	Quartile
医学	1
医学, 老年医学	1
医学, 细胞生物学	2

The secretome atlas of two mouse models of progeria

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Journal Info

Category	Quartile
GERIATRICS & GERONTOLOGY	1