Epigenetic Alterations and Reprogramming Potential in Aging

The role of epigenetics, which determine how your genes are expressed, is being increasingly implicated in aging, as is the potential of therapies that revert epigenetics back to those of a younger person.

What are epigenetic alterations?

The DNA in each of our cells is identical, with only some small variations, so why do our various organs and tissues look so different, and how do cells know what to become?

Our DNA is altered by the addition of epigenetic information that changes the gene expression of a cell, silencing or expressing certain genes in a cell as the situation demands. Essentially, epigenetics turn genes on and off in a cell, much like a light switch; however, in this case, there are hundreds of switches that each control their own genes.

This is why cells in different parts of our bodies know what they need to develop into and what to do. They are why a liver cell knows how to function, how an immune cell knows how to do its job, and how our heart cells know how to beat and keep us alive.

At a basic level, epigenetics act like instructions that tell each cell what to do, how to look, and how to behave, and there is increasing evidence that these instructions can also tell our cells to age.

A review of epigenetics in aging

Today, we want to highlight a new publication by Dr. David Sinclair and Dr. Alice Kane, both from Harvard Medical School, which reviews the role of epigenetic alterations in aging and the potential for resetting those changes via partial cellular reprogramming [1].

Abstract

The aging process results in significant epigenetic changes at all levels of chromatin and DNA organization. These include reduced global heterochromatin, nucleosome remodeling and loss, changes in histone marks, global DNA hypomethylation with CpG island hypermethylation, and the relocalization of chromatin modifying factors. Exactly how and why these changes occur is not fully understood, but evidence that these epigenetic changes affect longevity and may cause aging, is growing. Excitingly, new studies show that age-related epigenetic changes can be reversed with interventions such as cyclic expression of the Yamanaka reprogramming factors. This review presents a summary of epigenetic changes that occur in aging, highlights studies indicating that epigenetic changes may contribute to the aging process and outlines the current state of research into interventions to reprogram age-related epigenetic changes.

This publication contains a very comprehensive review of the literature and support for the role of epigenetics in aging. The presence of epigenetic alterations being a driver of aging does not invalidate the theory of wear and tear; just because aging can cause a cell to be reprogrammed does not imply that aging is the result of a program. The Hallmarks of Aging, published in 2013, proposes that epigenetic alterations are one of the primary reasons we age, and the evidence for this keeps growing with each passing year [2].

If epigenetic changes do contribute to the aging process, then there is the exciting possibility that we can prevent or even reverse those changes and intervene in a very upstream cause. Evidence of the prevention of epigenetic changes with aging can be seen with calorie restriction, sirtuin activation and small molecules. Amazingly, reprogramming appears to reverse age-related epigenetic changes and the effects of aging, both in vitro and in vivo. Clearly, in vivo reprogramming to address aging and age-related diseases is an early field but it is growing rapidly and holds considerable promise.

Conclusion

It is becoming increasingly clear that epigenetic alterations play a key role in aging and that they are amenable to interventions such as reprogramming via OSKM induction and other, similar approaches. Cells appear to function in an aged or young capacity depending on these epigenetic instructions; indeed, this is the basis of induced pluripotent stem cells, which are cells that can be taken even from aged individuals before being reprogrammed back into a younger functional state.

This is not to suggest that epigenetic alterations are a magic bullet for aging and that simply reverting them will completely solve it; it is very likely that they will not. However, this review and the evidence therein strongly support that epigenetic alterations are a major player in aging and that resetting epigenetics has a great deal of potential.

Literature

[1] Kane, A. E., & Sinclair, D. A. (2019). Epigenetic changes during aging and their reprogramming potential. Critical Reviews in Biochemistry and Molecular Biology, 1-23.

[2] López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194-1217.