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Abstract
There have been several reports of a significant positive correlation between paternal age and chromosome telomere length in offspring. Moreover, the telomeres in sperm cells of older men tend to be longer than in young men, and it has been concluded that telomeres lengthen in the testes during adulthood. This would be the first evidence of an increasing biological advantage with age, and therefore contradicts current models in which telomere shortening is a biomarker of aging. Instead, an alternative model of telomere erosion between human generations is discussed in which longer germ cell telomeres in old men result from their being members of a previous generation. Based on the well-known correlation between maternal age and the incidence of aneuploid pregnancies, it is hypothesized that telomere erosion predominantly operates in the female germline, leading to a carry-over effect for both sexes into the next generation. This theory fits well with experimental results that maternal age does not correlate with longer telomeres in offspring. An experimental design is presented to distinguish between the two possible scenarios leading to old fathers with long-telomered off-spring - namely lifetime lengthening in the testis versus transgenerational germline erosion. Consideration of net loss of telomeric DNA between human generations is supported by recent findings of a large difference in blood telomere length between different European populations of the same age, and is likely to have profound conse-quences for species evolution.
Keywords
Paternal age, Telomere erosion, Maternal age effect, Inheritance
Introduction
The termini of mammalian chromosomes are characterized by repetitive DNA sequences, which in association with a complex spectrum of bound proteins, constitute the telomeres. The repeating string is TTAGGG in all vertebrates, and a very similar or identical sequence is present in other taxa, indicating that telomeres are an ancient and con-served system of genome protection (1). Telomere structure is dynamic, and human telomeres shorten as a result of incomplete DNA replication every time a somatic cell divides. Accordingly, telomere erosion has been shown to limit the replicative potential of somatic cells ('mitotic clock'). These findings led many scientists to believe that the cause of aging had been found (2).
However, a major weakness of the telomere model of aging is that mean telomere length varies widely between individuals...