Biology

Is Age-Related Polyploidy a Beneficial Adaptation to a Damaged Environment?


Cells with abnormal chromosome counts, a state known as aneuploidy, are considered to be a problem. The evidence suggests that such cells accumulate with age, a form of damage and dysfunction that is associated with cellular senescence, and is expected to contribute to age-related degeneration and disease. Here, researchers argue that having duplicate chromosomes, polypoidy, might actually be protective, a beneficial adaptation that emerges in the damaged environment of aged tissues. This may be the case, and it may also be true that it is both protective and harmful. The weight of evidence to date continues to point to aneuploidy as an undesirable state regardless of whether there are more or fewer chromosomes in a cell.

Terminally differentiated postmitotic cells such as mature neurons and glia are long-lived and must cope with the accumulation of damage over the course of an animal’s lifespan. The mechanisms used by such long-lived cells to deal with aging-related damage are poorly understood. The brain of the fruit fly Drosophila melanogaster is an ideal context to examine this since the fly has a relatively short lifespan and the adult fly brain is nearly entirely postmitotic with well understood development and excellent tools for genetic manipulations.

Polyploidy can confer an increased biosynthetic capacity to cells and resistance to DNA damage induced cell death. Several studies have noted neurons and glia in the adult fly brain with large nuclei and in some cases neurons and glia of other insect species in the adult central nervous system (CNS) are known to be polyploid. Rare instances of neuronal polyploidy have been reported in vertebrates under normal conditions and even in the CNS of mammals.

Polyploidization is employed in response to tissue damage and helps maintain organ size. Therefore, polyploidy may be a strategy to deal with damage accumulated with age in the brain, a tissue with very limited cell division potential. Here we show that polyploid cells accumulate in the adult fly brain and that this proportion of polyploidy increases as the animals approach middle-age. We show that multiple types of neurons and glia which are diploid at eclosion which become polyploid specifically in the adult brain. We have found that the optic lobes of the brain contribute to most of the observed polyploidy. We also observe increased DNA damage with age, and show that inducing oxidative stress and exogenous DNA damage can lead to increased levels of polyploidy. We find that polyploid cells in the adult brain are resistant to DNA damage-induced cell death and propose a potentially protective role for polyploidy in neurons and glia in adult Drosophila melanogaster brains.

Link: https://doi.org/10.7554/eLife.54385

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