Institute for Aging Research, Department of Medicine, Divisions of Endocrinology and Geriatrics, Department of Genetics, Albert Einstein College of Medicine, Bronx, New York 10461, USA
Institute for Aging Research, Department of Medicine, Divisions of Endocrinology and Geriatrics, Department of Genetics, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Cold Spring Harb Perspect Med. 2023 Sep 1;13(9):a041204. doi: 10.1101/cshperspect.a041204.
Humans age at different rates and families with exceptional longevity provide an opportunity to understand why some people age slower than others. Unique features exhibited by centenarians include a family history of extended life span, compression of morbidity with resultant extension of health span, and longevity-associated biomarker profiles. These biomarkers, including low-circulating insulin-like growth factor 1 (IGF-1) and elevated high-density lipoprotein (HDL) cholesterol levels, are associated with functional genotypes that are enriched in centenarians, suggesting that they may be causative for longevity. While not all genetic discoveries from centenarians have been validated, in part due to exceptional life span being a rare phenotype in the general population, the APOE2 and FOXO3a genotypes have been confirmed in a number of populations with exceptional longevity. However, life span is now recognized as a complex trait and genetic research methods to study longevity are rapidly extending beyond classical Mendelian genetics to polygenic inheritance methodologies. Moreover, newer approaches are suggesting that pathways that have been recognized for decades to control life span in animals may also regulate life span in humans. These discoveries led to strategic development of therapeutics that may delay aging and prolong health span.
人类衰老的速度不同，拥有长寿家族的人提供了一个了解为什么有些人比其他人衰老得慢的机会。百岁老人表现出的独特特征包括家族长寿史、发病率压缩导致健康寿命延长，以及与长寿相关的生物标志物特征。这些生物标志物包括循环胰岛素样生长因子 1（IGF-1）水平低和高密度脂蛋白（HDL）胆固醇水平高，与功能性基因型有关，这些基因型在百岁老人中较为丰富，表明它们可能是长寿的原因。虽然并非所有从百岁老人中发现的遗传信息都得到了验证，部分原因是因为在一般人群中，超长寿命是一种罕见的表型，但 APOE2 和 FOXO3a 基因型已在多个具有超长寿命的人群中得到证实。然而，现在人们已经认识到寿命是一种复杂的特征，研究长寿的遗传研究方法正在迅速从经典的孟德尔遗传学扩展到多基因遗传方法。此外，更新的方法表明，几十年来被认为可以控制动物寿命的途径也可能调节人类的寿命。这些发现促使人们开发出可能延缓衰老和延长健康寿命的治疗方法。
