Aging and Beta Cell Function

Getting old may not be all bad for patients with diabetes. A cellular aging process may, unexpectedly, enhance insulin secretion by causing pancreatic beta cells to work harder, according to a new study.

"The findings suggest that what we call aging is in fact a continuum, starting with a maturation process that actually improves the function of cells and tissue, at the expense of regenerative potential. This has important implications for how we think about beta cell function and dysfunction in diabetes" said Dr. Ronny Helman, who conducted the study as a postdoctoral fellow at the Hebrew University of Jerusalem.

Cellular senescence is thought to contribute to age-associated deterioration of tissue physiology. The senescence effector p16^Ink4a is expressed in pancreatic beta cells during aging and limits their proliferative potential.

This activity is seen as having a negative effect. Inability of these cells to divide can contribute to diabetes since beta cells are responsible for secreting insulin and their loss causes diabetes. However, it was unknown whether senescent beta cells could continue functioning at all.

“We found that beta cell-specific activation of p16^Ink4a in transgenic mice enhances glucose-stimulated insulin secretion. In mice with diabetes, this leads to improved glucose homeostasis, providing an unexpected functional benefit,” stated the authors.

They also found that islets from human adults contain p16^Ink4a-expressing senescent beta cells and that senescence induced by p16^Ink4a in a human beta cell line increases insulin secretion.

“Our findings reveal a novel role for p16^Ink4a and cellular senescence in promoting insulin secretion by beta cells and in regulating normal functional tissue maturation with age,” they stated.

"Senescence of cells is generally thought to represent a state in which cells lose their functionality, and contribute to tissue aging and disease. It was therefore very striking to observe that when beta cells enter this state during normal aging, the program allows them to function better, rather than worse," said Dr. Ittai Ben-Porath, who holds the Jacob and Lena Joels Memorial Foundation Senior Lectureship for Excellence in the Life and Medical Sciences, at the Institute for Medical Research Israel-Canada in the Faculty of Medicine at The Hebrew University of Jerusalem.

The novel findings indicate for the first time that the function of beta cells actually improves during healthy aging, at least in some aspects. The study also provides a basic understanding about what happens to beta cells during aging, which is a tradeoff between their ability to divide and regenerate and their ability to function well.

The authors suggest that the discovery that senescence regulates insulin secretion may have broad implications for the understanding and treatment of diabetes. It highlights a new mechanism by which beta cell function and insulin secretion can be enhanced, and suggests that drugs that can affect cell division and senescence may influence beta cell function. It is conceivable that tools that can activate senescence could be implemented for better treatment of diabetes.

Reference: Helman A, et al. p16^Ink4a-induced senescence of pancreatic beta cells enhances insulin secretion. Nature Med. 2016;22:412-420.