Project Summary
Age-related diseases are among the leading causes of morbidity, mortality, and healthcare expenditure
both in the United States and the world at large. Age-associated declines in fertility are one of the earliest and
most common symptoms of aging in both men and women, and almost one-fourth of couples between the
ages of 18 and 45 suffer from impaired fertility or infertility. Although assisted reproductive technology can help
couples with impaired fertility produce viable offspring, it can be very expensive and does not treat the root of
the problem: germline aging. Existing literature on aging is relatively sparse, focusing on conventional model
organisms with relatively short lifespans and how various treatments can slow their decline rather than prevent
it entirely, or even reverse aging. The negligibly-senescent, highly-regenerative, hermaphroditic planarian S.
mediterranea presents a unique model system to study germline aging because it is one of the few species to
actively reverse an aging phenotype. I have observed that S. mediterranea experiences an age-related decline
in its fertility that can be reversed by bisecting the planarians and allowing them to regenerate. The overall goal
of my project is to determine how aging impairs fertility in S. mediterranea, and how regeneration overcomes
this impairment. Based on preliminary data, I hypothesize that age-associated molecular damage
accumulates in late gonadal precursor cells of the testes and (especially) ovaries, compromising the
production of mature germ cells, and that during regeneration these impaired cells are replaced by
functional equivalents to restore fertility. To evaluate this hypothesis, I will seek to address the following
specific aims. Aim 1: I will assay changes in markers of gametogenesis to determine how germ and niche cell
population are affected by aging and rejuvenation. Aim 2: I will use a panel of molecular biomarkers on
isolated gonads to determine if age-associated biomarkers accumulate in the gonads over time, and if
regeneration restores the gonads to a more youthful state. Aim 3: I will use selective mating experiments to
determine if impairments in fertility are due to defects in the testes, ovaries, or both. From these experiments, I
will learn more about the cellular, molecular, and physiological causes of germline aging in S. mediterranea,
and how regeneration manages to reverse them. These results will also help us understand why other
organisms are unable to prevent age-related gonadal degeneration, and potentially lay the groundwork for
more robust fertility treatments that extend or even restore fertility in humans.