Age-dependent energy metabolism and transcriptome changes in urine-derived stem cells

IF 5.3 3区医学 Q2 CELL BIOLOGY

Mechanisms of Ageing and Development Pub Date : 2024-01-22 DOI:10.1016/j.mad.2024.111912

Elisabete Ferreiro , Mariana Monteiro , Francisco Pereira , Cristina Barroso , Conceição Egas , Paula Macedo , Jorge Valero , Vilma A. Sardão , Paulo J. Oliveira

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Abstract

The global population over 60 years old is projected to reach 1.5 billion by 2050. Understanding age-related disorders and gender-specificities is crucial for a healthy aging. Reliable age-related biomarkers are needed, preferentially obtained through non-invasive methods. Urine-derived stem cells (UDSCs) can be easily obtained, although a detailed bioenergetic characterization, according to the donor aging, remain unexplored. UDSCs were isolated from young and elderly adult women (22–35 and 70–94 years old, respectively). Surprisingly, UDSCs from elderly subjects exhibited significantly higher maximal oxygen consumption and bioenergetic health index than those from younger individuals, evaluated through oxygen consumption rate. Exploratory data analysis methods were applied to engineer a minimal subset of features for the classification and stratification of UDSCs. Additionally, RNAseq of UDSCs was performed to identify age-related transcriptional changes. Transcriptional analysis revealed downregulation of genes related to glucuronidation and estrogen metabolism, and upregulation of inflammation-related genes in UDSCs from elderly individuals. This study demonstrates unexpected differences in the UDSCs’ OCR between young and elderly individuals, revealing improved bioenergetics in concurrent with an aged-like transcriptome signature. UDSCs offer a non-invasive model for studying age-related changes, holding promise for aging research and therapeutic studies.

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尿液衍生干细胞随年龄变化的能量代谢和转录组变化

预计到 2050 年，全球 60 岁以上人口将达到 15 亿。了解与年龄相关的疾病和性别特异性对于健康老龄化至关重要。我们需要可靠的与年龄相关的生物标志物，这些标志物最好通过非侵入性方法获得。尿源干细胞（UDSCs）很容易获得，但根据供体的衰老程度进行详细的生物能表征仍有待探索。我们从年轻和年长的成年女性（分别为 22-35 岁和 70-94 岁）身上分离出尿源性干细胞。令人惊讶的是，通过耗氧率评估，来自老年受试者的 UDSCs 的最大耗氧量和生物能健康指数明显高于来自年轻人的 UDSCs。探索性数据分析方法被用于设计用于 UDSCs 分类和分层的最小特征子集。此外，还对 UDSCs 进行了 RNAseq 分析，以确定与年龄相关的转录变化。转录分析表明，在老年人的 UDSCs 中，与葡萄糖醛酸化和雌激素代谢相关的基因下调，而与炎症相关的基因上调。这项研究表明，UDSCs的OCR在年轻人和老年人之间存在意想不到的差异，揭示了生物能的改善与类似老年人的转录组特征。UDSCs 为研究与年龄有关的变化提供了一种非侵入性模型，为老龄化研究和治疗研究带来了希望。

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来源期刊

Mechanisms of Ageing and Development 医学-老年医学

CiteScore

11.10

自引率

1.90%

发文量

审稿时长

32 days

期刊介绍： Mechanisms of Ageing and Development is a multidisciplinary journal aimed at revealing the molecular, biochemical and biological mechanisms that underlie the processes of aging and development in various species as well as of age-associated diseases. Emphasis is placed on investigations that delineate the contribution of macromolecular damage and cytotoxicity, genetic programs, epigenetics and genetic instability, mitochondrial function, alterations of metabolism and innovative anti-aging approaches. For all of the mentioned studies it is necessary to address the underlying mechanisms. Mechanisms of Ageing and Development publishes original research, review and mini-review articles. The journal also publishes Special Issues that focus on emerging research areas. Special issues may include all types of articles following peered review. Proposals should be sent directly to the Editor-in-Chief.