Why Would Pancreatic Cell Size Correlate Well with Mammalian Species Longevity?

Researchers recently found that the size of pancreatic cells is inversely correlated with species longevity, given data obtained from a few dozen different types of mammal. Since this is an unexpected new discovery, the paper here contains little more than an initial educated guess at why this might be the case. At first glance this metric doesn't obviously relate to any of the usual mechanisms linking the operation of cellular metabolism with pace of aging, and thus I expect that we'll have to wait for some years of further investigation and theorizing to learn more.

How organs reach and maintain their proper size is a major question in biology. Organ size is the product of total cell number, average cell size, and volume of the extracellular space. Cell number is considered the main determinant of organ size, and differences in cell number explain much of the size difference between organisms, such as mice and humans. However, within a given species, different organs vary considerably in the relative contribution of cell number and cell size to total organ size. For example, the increase in the total mass of blood from birth to adult life results from larger cell numbers, while postnatal growth of cardiac and skeletal muscle largely relies on increased cell size.

Despite the major differences in final size among mammalian species, the molecular and cellular mechanisms underlying organ growth are usually thought to be highly similar. In the case of the pancreas, embryonic progenitor cells initially proliferate and differentiate to form a miniature organ. After birth, progenitor cells largely disappear. The current consensus is that postnatal growth of the pancreas, in mice and by extension also in humans, relies on simple duplication of differentiated cells, consistent with the classic description of the pancreas as an "expanding tissue."

The size of cells in the adult pancreas is recognized to be plastic. For example, acinar cells shrink when luminal nutrients are not available, and beta cell size increases transiently in pregnant rodents. However, increased cell size is not typically considered a significant contributor to normal postnatal pancreas growth. Here we report surprising differences in the mode of postnatal pancreas growth among different mammals. While the human pancreas grows by pure hyperplasia, the rodent pancreas grows mostly by cellular hypertrophy. Acinar cells of the salivary glands present a similar trend, namely larger cells in mice compared with humans. Finally, we identify a surprising negative correlation between acinar cell size and organismal lifespan, based on analysis of 24 mammalian species.

Our findings suggest that the associations of metabolic rate and body weight with lifespan are mediated by differences in cell size. This suggests that animals employing acinar hypertrophy live shorter lifespans. What might be the evolutionary advantage of hypertrophy as a mode of organ growth? We propose that the key is the speed of postnatal growth. Both humans and mice (and their organs, including the pancreas) grow approximately 15-fold from birth to reproductive age; however, this age is reached ∼100 times faster in mice. We hypothesize that cellular hypertrophy contributes to the rapid growth of short-lived mammals. Indeed, the rate of postnatal growth is negatively correlated with lifespan, and this correlation is eliminated when controlling for cell size. This result supports a model whereby cellular hypertrophy promotes rapid postnatal growth rate and earlier sexual maturity at the expense of lifespan.

Link: https://doi.org/10.1016/j.devcel.2018.05.024

Comments

I don't think that the mechanism is all that obscure. If the growth signal is larger and there is a rate limitation on cellular division, hypertrophy is what will happen. Of course the end result of this is overwhelming of the lysosomes and cellular senescence. Slower growth gives the cells time to deal with the byproducts of metabolism and avoid cellular senescence for longer.

Posted by: Mark at June 20th, 2018 10:09 AM

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