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人类 LAV-BPIFB4 基因治疗对老年小鼠的表观遗传钟和健康的影响。

Effects of Human LAV-BPIFB4 Gene Therapy on the Epigenetic Clock and Health of Aged Mice.

机构信息

Advanced Technology Center for Aging Research, IRCCS INRCA, 60121 Ancona, Italy.

Laboratory of Epigenetics, Istituti Clinici Scientifici Maugeri IRCCS, Via Maugeri 10, 27100 Pavia, Italy.

出版信息

Int J Mol Sci. 2023 Mar 30;24(7):6464. doi: 10.3390/ijms24076464.

DOI:10.3390/ijms24076464
PMID:37047437
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10095240/
Abstract

The homozygous genotype of the Longevity-Associated Variant (LAV) in Bactericidal/Permeability-Increasing Fold-Containing Family B member 4 (BPIFB4) is enriched in long-living individuals of three independent populations and its genetic transfer in C57BL/6J mice showed a delay in frailty progression and improvement of several biomarkers of aging and multiple aspects of health. The C57BL/6J strain is a suitable model for studying therapies aimed at extending healthy aging and longevity due to its relatively short lifespan and the availability of aging biomarkers. Epigenetic clocks based on DNA methylation profiles are reliable molecular biomarkers of aging, while frailty measurement tools are used to evaluate overall health during aging. In this study, we show that the systemic gene transfer of LAV-BPIFB4 in aged C57BL/6J mice was associated with a significant reduction in the epigenetic clock-based biological age, as measured by a three CpG clock method. Furthermore, LAV-BPIFB4 gene transfer resulted in an improvement of the Vitality Score with a reduction in the Frailty Index. These findings further support the use of LAV-BPIFB4 gene therapy to induce beneficial effects on epigenetic mechanisms associated with aging and frailty in aged mice, with potential implications for future therapies to prevent frailty in humans.

摘要

长寿相关变异体（LAV）在杀菌/通透性增加折叠家族 B 成员 4（BPIFB4）中的纯合基因型在三个独立人群的长寿个体中富集，其在 C57BL/6J 小鼠中的遗传转移显示出虚弱进展的延迟和衰老和多种健康状况的多个方面的生物标志物的改善。C57BL/6J 品系由于其相对较短的寿命和衰老生物标志物的可用性，是研究旨在延长健康衰老和长寿的治疗方法的合适模型。基于 DNA 甲基化谱的表观遗传钟是衰老的可靠分子生物标志物，而虚弱测量工具用于评估衰老过程中的整体健康状况。在这项研究中，我们表明，在年老的 C57BL/6J 小鼠中全身基因转移 LAV-BPIFB4 与基于三个 CpG 时钟方法的表观遗传时钟生物年龄的显著减少有关。此外，LAV-BPIFB4 基因转移导致活力评分的改善，虚弱指数降低。这些发现进一步支持使用 LAV-BPIFB4 基因治疗来诱导与衰老和虚弱相关的表观遗传机制的有益影响年老小鼠，这可能对预防人类虚弱的未来治疗具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbd8/10095240/42ddc5661cf2/ijms-24-06464-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbd8/10095240/e997712e5e8f/ijms-24-06464-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbd8/10095240/50dce1758d26/ijms-24-06464-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbd8/10095240/42ddc5661cf2/ijms-24-06464-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbd8/10095240/e997712e5e8f/ijms-24-06464-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbd8/10095240/50dce1758d26/ijms-24-06464-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbd8/10095240/42ddc5661cf2/ijms-24-06464-g003.jpg

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