Department of Anthropology, Northwestern University, Evanston, IL 60208, USA.
Proc Natl Acad Sci U S A. 2012 Jun 26;109(26):10251-6. doi: 10.1073/pnas.1202092109. Epub 2012 Jun 11.
Telomeres are repeating DNA sequences at the ends of chromosomes that protect and buffer genes from nucleotide loss as cells divide. Telomere length (TL) shortens with age in most proliferating tissues, limiting cell division and thereby contributing to senescence. However, TL increases with age in sperm, and, correspondingly, offspring of older fathers inherit longer telomeres. Using data and samples from a longitudinal study from the Philippines, we first replicate the finding that paternal age at birth is associated with longer TL in offspring (n = 2,023, P = 1.84 × 10(-6)). We then show that this association of paternal age with offspring TL is cumulative across multiple generations: in this sample, grandchildren of older paternal grandfathers at the birth of fathers have longer telomeres (n = 234, P = 0.038), independent of, and additive to, the association of their father's age at birth with TL. The lengthening of telomeres predicted by each year that the father's or grandfather's reproduction are delayed is equal to the yearly shortening of TL seen in middle-age to elderly women in this sample, pointing to potentially important impacts on health and the pace of senescent decline in tissues and systems that are cell-replication dependent. This finding suggests a mechanism by which humans could extend late-life function as average age at reproduction is delayed within a lineage.
端粒是染色体末端重复的 DNA 序列，可在细胞分裂时保护和缓冲基因免受核苷酸丢失。在大多数增殖组织中，端粒长度（TL）随年龄的增长而缩短，限制了细胞分裂，从而导致衰老。然而，在精子中，TL 随年龄的增长而增加，相应地，年龄较大的父亲的后代继承了更长的端粒。利用来自菲律宾一项纵向研究的数据和样本，我们首先复制了这样一种发现，即父亲的出生年龄与后代的 TL 较长有关（n = 2,023，P = 1.84 × 10(-6)）。然后，我们表明，父亲年龄与后代 TL 的这种关联是跨多代累积的：在这个样本中，父亲出生时年龄较大的祖父的孙子孙女的端粒较长（n = 234，P = 0.038），与他们父亲的出生年龄与 TL 的关联无关且具有累加性。由父亲或祖父的繁殖每推迟一年而预测的端粒延长，与该样本中从中年到老年的女性中观察到的 TL 每年缩短相等，这表明对与细胞复制相关的组织和系统的健康和衰老下降速度有潜在的重要影响。这一发现为人类提供了一种机制，可以延长生殖平均年龄在谱系内推迟时的晚年功能。
