Sebastiani Paola, Riva Alberto, Montano Monty, Pham Phillip, Torkamani Ali, Scherba Eugene, Benson Gary, Milton Jacqueline N, Baldwin Clinton T, Andersen Stacy, Schork Nicholas J, Steinberg Martin H, Perls Thomas T
Department of Biostatistics, Boston University School of Public Health Boston, MA, USA.
Front Genet. 2012 Jan 3;2:90. doi: 10.3389/fgene.2011.00090. eCollection 2011.
Supercentenarians (age 110+ years old) generally delay or escape age-related diseases and disability well beyond the age of 100 and this exceptional survival is likely to be influenced by a genetic predisposition that includes both common and rare genetic variants. In this report, we describe the complete genomic sequences of male and female supercentenarians, both age >114 years old. We show that: (1) the sequence variant spectrum of these two individuals' DNA sequences is largely comparable to existing non-supercentenarian genomes; (2) the two individuals do not appear to carry most of the well-established human longevity enabling variants already reported in the literature; (3) they have a comparable number of known disease-associated variants relative to most human genomes sequenced to-date; (4) approximately 1% of the variants these individuals possess are novel and may point to new genes involved in exceptional longevity; and (5) both individuals are enriched for coding variants near longevity-associated variants that we discovered through a large genome-wide association study. These analyses suggest that there are both common and rare longevity-associated variants that may counter the effects of disease-predisposing variants and extend lifespan. The continued analysis of the genomes of these and other rare individuals who have survived to extremely old ages should provide insight into the processes that contribute to the maintenance of health during extreme aging.
超级百岁老人(年龄在110岁及以上)通常在100岁之后能很好地延缓或避免与年龄相关的疾病和残疾,这种超长的生存期可能受到遗传易感性的影响,其中包括常见和罕见的基因变异。在本报告中,我们描述了两位年龄均超过114岁的男性和女性超级百岁老人的完整基因组序列。我们发现:(1)这两个人的DNA序列变异谱与现有的非超级百岁老人基因组在很大程度上具有可比性;(2)这两个人似乎并未携带文献中已报道的大多数已确定的与人类长寿相关的变异;(3)相对于迄今为止测序的大多数人类基因组,他们具有数量相当的已知疾病相关变异;(4)这些人所拥有的变异中约1%是新的,可能指向与超长寿命相关的新基因;(5)通过大规模全基因组关联研究发现,这两个人在长寿相关变异附近的编码变异都有所富集。这些分析表明,存在常见和罕见的与长寿相关的变异,它们可能抵消疾病易感变异的影响并延长寿命。对这些以及其他活到极高年龄的罕见个体的基因组进行持续分析,应该能够深入了解在极端衰老过程中有助于维持健康的过程。