虚弱的遗传学：长寿视角。
Genetics of frailty: A longevity perspective.
机构信息
Department of Neurology, Albert Einstein College of Medicine, Bronx, New York.
Department of Neurology, Albert Einstein College of Medicine, Bronx, New York; Department of Medicine, Albert Einstein College of Medicine, Bronx, New York.
出版信息
Transl Res. 2020 Jul;221:83-96. doi: 10.1016/j.trsl.2020.03.005. Epub 2020 Mar 19.
Abstract
Frailty is a complex late life phenotype characterized by cumulative declines in multiple physiological systems that increases the risk for disability and mortality. The biological changes associated with aging are risk factors for frailty as well as for complex diseases; whereas longevity is assumed to be an outcome of protective biological mechanisms. Understanding the interplay between biological alterations associated with aging and protective mechanisms associated with longevity in the context of frailty may help guide development of interventions to increase healthspan and promote successful aging. The complexity of these phenotypes and relatively low heritability in studies are the main roadblocks in deciphering genetic mechanisms of these age associated conditions. We review genetic research related to frailty, and discuss the possible intertwined biology of frailty and longevity.
摘要
虚弱是一种复杂的晚年表型，其特征是多个生理系统的累积衰退，增加了残疾和死亡的风险。与衰老相关的生物学变化既是虚弱的危险因素，也是复杂疾病的危险因素；而长寿则被认为是保护生物学机制的结果。了解与衰老相关的生物学变化和与长寿相关的保护机制在虚弱中的相互作用，可能有助于指导干预措施的制定，以增加健康寿命并促进成功老龄化。这些表型的复杂性以及研究中相对较低的遗传性是破译与年龄相关疾病相关遗传机制的主要障碍。我们回顾了与虚弱相关的遗传研究，并讨论了虚弱和长寿的生物学可能交织在一起。
相似文献
1
Genetics of frailty: A longevity perspective.虚弱的遗传学：长寿视角。
Transl Res. 2020 Jul;221:83-96. doi: 10.1016/j.trsl.2020.03.005. Epub 2020 Mar 19.
2
Quantification of healthspan in aging mice: introducing FAMY and GRAIL.衰老小鼠健康寿命的量化：介绍 FAMY 和 GRAIL。
Geroscience. 2024 Oct;46(5):4203-4215. doi: 10.1007/s11357-024-01200-5. Epub 2024 May 17.
3
Frailty index as a biomarker of lifespan and healthspan: Focus on pharmacological interventions.衰弱指数作为寿命和健康跨度的生物标志物：关注药物干预。
Mech Ageing Dev. 2019 Jun;180:42-48. doi: 10.1016/j.mad.2019.03.005. Epub 2019 Mar 26.
4
Sex differences in frailty: Comparisons between humans and preclinical models.性别与虚弱：人类与临床前模型的比较。
Mech Ageing Dev. 2021 Sep;198:111546. doi: 10.1016/j.mad.2021.111546. Epub 2021 Jul 26.
5
Collagens and elastin genetic variations and their potential role in aging-related diseases and longevity in humans.胶原和弹性蛋白的遗传变异及其在与衰老相关的疾病和人类长寿中的潜在作用。
Exp Gerontol. 2020 Jan;129:110781. doi: 10.1016/j.exger.2019.110781. Epub 2019 Nov 15.
6
LAV-BPIFB4 associates with reduced frailty in humans and its transfer prevents frailty progression in old mice.LAV-BPIFB4与人类虚弱程度降低相关，其转移可防止老年小鼠的虚弱进展。
Aging (Albany NY). 2019 Aug 28;11(16):6555-6568. doi: 10.18632/aging.102209.
7
Healthspan, translation, and new outcomes for animal studies of aging.健康寿命、翻译以及衰老动物研究的新成果。
J Gerontol A Biol Sci Med Sci. 2009 Feb;64(2):209-12. doi: 10.1093/gerona/gln063. Epub 2009 Feb 5.
8
G-395A polymorphism in the promoter region of the KLOTHO gene associates with frailty among the oldest-old.KLOTHO 基因启动子区 G-395A 多态性与超高龄人群的虚弱有关。
Sci Rep. 2018 Apr 30;8(1):6735. doi: 10.1038/s41598-018-25040-4.
9
Frailty and biological age. Which best describes our aging and longevity?虚弱和生物年龄。哪个更能描述我们的衰老和长寿？
Mol Aspects Med. 2024 Aug;98:101291. doi: 10.1016/j.mam.2024.101291. Epub 2024 Jul 1.
10
Estimating Biological Age in the Singapore Longitudinal Aging Study.估算新加坡纵向老龄化研究中的生物年龄。
J Gerontol A Biol Sci Med Sci. 2020 Sep 25;75(10):1913-1920. doi: 10.1093/gerona/glz146.
引用本文的文献
1
A Frailty-Based Plasma Proteomic Signature Capturing Overall Health and Well-Being in Older Adults.一种基于衰弱的血浆蛋白质组学特征可反映老年人的整体健康状况。
Aging Cell. 2025 Sep;24(9):e70144. doi: 10.1111/acel.70144. Epub 2025 Aug 4.
2
The association of a polygenic lifespan score with the risk of common age-related diseases and mortality.多基因寿命评分与常见年龄相关疾病风险及死亡率的关联。
J Gerontol A Biol Sci Med Sci. 2025 Aug 23;80(9). doi: 10.1093/gerona/glaf156.
3
Bidirectional genetic links between chronic obstructive pulmonary disease and frailty: Genome-wide association study insights.慢性阻塞性肺疾病与衰弱之间的双向遗传联系：全基因组关联研究见解
PLoS One. 2025 May 29;20(5):e0320304. doi: 10.1371/journal.pone.0320304. eCollection 2025.
4
Metallothionein-1A (MT1A) Gene Variability May Play a Role in Female Frailty: A Preliminary Study.金属硫蛋白-1A（MT1A）基因变异性可能在女性虚弱中起作用：一项初步研究。
Genes (Basel). 2024 Dec 26;16(1):15. doi: 10.3390/genes16010015.
5
Genetic and phenotypic associations of frailty with cardiovascular indicators and behavioral characteristics.衰弱与心血管指标及行为特征的遗传和表型关联。
J Adv Res. 2025 May;71:263-277. doi: 10.1016/j.jare.2024.06.012. Epub 2024 Jun 9.
6
Multi-polygenic prediction of frailty highlights chronic pain and educational attainment as key risk and protective factors.衰弱的多基因预测突出了慢性疼痛和受教育程度是关键的风险因素和保护因素。
medRxiv. 2024 May 31:2024.05.31.24308260. doi: 10.1101/2024.05.31.24308260.
7
To Be Frail or Not to Be Frail: This Is the Question-A Critical Narrative Review of Frailty.衰弱与否：这是个问题——对衰弱的批判性叙述性综述
J Clin Med. 2024 Jan 26;13(3):721. doi: 10.3390/jcm13030721.
8
Multivariate genome-wide analysis of aging-related traits identifies novel loci and new drug targets for healthy aging.多变量全基因组分析与衰老相关的特征，确定了新的与健康衰老相关的基因座和新的药物靶点。
Nat Aging. 2023 Aug;3(8):1020-1035. doi: 10.1038/s43587-023-00455-5. Epub 2023 Aug 7.
9
Utilizing multimodal approach to identify candidate pathways and biomarkers and predicting frailty syndrome in individuals from UK Biobank.利用多模态方法鉴定候选途径和生物标志物，并预测英国生物银行个体的衰弱综合征。
Geroscience. 2024 Feb;46(1):1211-1228. doi: 10.1007/s11357-023-00874-7. Epub 2023 Jul 31.
10
The degree of frailty as a translational measure of health in aging.衰弱程度作为衡量衰老健康的转化指标。
Nat Aging. 2021 Aug;1(8):651-665. doi: 10.1038/s43587-021-00099-3. Epub 2021 Aug 12.
本文引用的文献
1
A genome-wide association study of the frailty index highlights brain pathways in ageing.一项针对虚弱指数的全基因组关联研究强调了大脑在衰老过程中的作用。
Aging Cell. 2021 Sep;20(9):e13459. doi: 10.1111/acel.13459. Epub 2021 Aug 25.
2
Varying Effects of APOE Alleles on Extreme Longevity in European Ethnicities.APOE 等位基因对欧洲裔人群极端长寿的影响各异。
J Gerontol A Biol Sci Med Sci. 2019 Nov 13;74(Suppl_1):S45-S51. doi: 10.1093/gerona/glz179.
3
The genetics of human ageing.人类衰老的遗传学。
Nat Rev Genet. 2020 Feb;21(2):88-101. doi: 10.1038/s41576-019-0183-6. Epub 2019 Nov 5.
4
Physical frailty and decline in general and specific cognitive abilities: the Lothian Birth Cohort 1936.身体虚弱和一般及特定认知能力下降：洛锡安出生队列 1936 年研究。
J Epidemiol Community Health. 2020 Feb;74(2):108-113. doi: 10.1136/jech-2019-213280. Epub 2019 Nov 5.
5
Apolipoprotein ε4 allele is associated with frailty syndrome: results from the hellenic longitudinal investigation of ageing and diet study.载脂蛋白 E4 等位基因与虚弱综合征相关：来自希腊老龄化和饮食研究的纵向研究结果。
Age Ageing. 2019 Nov 1;48(6):917-921. doi: 10.1093/ageing/afz098.
6
Neuroticism as a Predictor of Frailty in Old Age: A Genetically Informative Approach.神经质作为老年脆弱的预测因子：一种遗传信息方法。
Psychosom Med. 2019 Nov/Dec;81(9):799-807. doi: 10.1097/PSY.0000000000000742.
7
Frailty and Risk of Incident Motoric Cognitive Risk Syndrome.衰弱与运动认知风险综合征事件风险。
J Alzheimers Dis. 2019;71(s1):S85-S93. doi: 10.3233/JAD-190517.
8
A meta-analysis of genome-wide association studies identifies multiple longevity genes.一项全基因组关联研究的荟萃分析确定了多个长寿基因。
Nat Commun. 2019 Aug 14;10(1):3669. doi: 10.1038/s41467-019-11558-2.
9
Interleukin 10 gene polymorphisms and frailty syndrome in elderly Mexican people: (Sadem study).白细胞介素 10 基因多态性与老年墨西哥人衰弱综合征的关系：（Sadem 研究）。
Mol Genet Genomic Med. 2019 Sep;7(9):e918. doi: 10.1002/mgg3.918. Epub 2019 Aug 6.
10
Genes Related to Education Predict Frailty Among Older Adults in the United States.与教育相关的基因可预测美国老年人的脆弱程度。
J Gerontol B Psychol Sci Soc Sci. 2021 Jan 1;76(1):173-183. doi: 10.1093/geronb/gbz092.
Zotero 插件