Testing for paternal influences on offspring telomere length in a human cohort in the Philippines

Abstract

Objectives: Telomeres, emerging biomarkers of aging, are comprised of DNA repeats located at chromosomal ends that shorten with cellular replication and age in most human tissues. In contrast, spermatocyte telomeres lengthen with age. These changes in telomere length (TL) appear to be heritable, as older paternal ages of conception (PAC) predict longer offspring TL. Mouse-model studies raise questions about the potential for effects of paternal experiences on human offspring TL, as they suggest that smoking, inflammation, DNA damage, and stressors all shorten sperm TL. Here, we examined whether factors from the paternal environment predict offspring TL as well as interact with PAC to predict offspring TL.Materials and Methods: Using data from the Philippines, we tested if smoking, psychosocial stressors, or shorter knee height (a measure of early life adversity) predict shorter offspring TL. We also tested if these interacted with PAC in predicting offspring TL.Results: While we did not find the predicted associations, we observed a trend toward fathers with shorter knee height having offspring with longer TL. In addition, we found that knee height interacted with PAC to predict offspring TL. Specifically, fathers with shorter knee heights showed a stronger positive effect of PAC on offspring TL.Discussion: While the reasons for these associations remain uncertain, shorter knee height is characteristic of earlier puberty. Since spermatocyte TL increases with the production of sperm, we speculate that individuals with earlier puberty, and its concomitant commencement of production of sperm, had more time to accumulate longer sperm telomeres. K E Y W O R D Sepigenetics, intergenerational effects, intergenerational inertia, intergenerational plasticity, senescence

Difference in Relative Telomere Length Between Sudanese and Chinese Individuals

“…The relative telomere length has been related to various illness conditions and more affected by environmental and genetic factors (2,4,6,26,27). Most studies describe the relative telomere length among different populations, but not as a marker index of difference between individuals, or even among Sudanese and Chinese individuals as more clearly various ethnic groups.…”

“…The length of telomeres can differ between individuals and even between individuals of the similar or same age. In addition, the difference in the relative telomere length might be associated with the variations in living environments or genetic factors between individuals (6,26,27).…”

“…The length of telomeres between individuals can vary at birth and between individuals of the same age (23,24). The length of telomeres can be stated or predicted by the parental length of telomeres, and it is stronger with a paternal effect than a maternal influence (22,(25)(26)(27).…”

What is the biological significance of DNA methylation-based estimators of telomere length? An assessment using the paternal age at conception effect and measures of external validity

“…Household income values were log (base 10) transformed. Urbanicity is a continuous measure derived from community-level data to measure the urban-rural continuum in the Philippines (Dahly and Adair, 2007) that has been found to be associated with TL in past analyses (Tennyson et al, 2018;Rej et al, 2019;Eisenberg et al, 2020).…”

Cross‐Generational Effects of Parental Age on Offspring Longevity: Are Telomeres an Important Underlying Mechanism?

“…[ 88,89 ] There is also recent evidence in humans that the effects of paternal age on offspring telomeres depends on the growth conditions experienced by the offspring during development. [ 90 ] Thus, the influence of parental age on offspring telomeres can vary depending on environmental circumstances and aspects of parental and offspring state. Given this, future studies should be conducted across a range of environmental conditions.…”