Changes in Regenerative Capacity through Lifespan

Abstract

Most organisms experience changes in regenerative abilities through their lifespan. During aging, numerous tissues exhibit a progressive decline in homeostasis and regeneration that results in tissue degeneration, malfunction and pathology. The mechanisms responsible for this decay are both cell intrinsic, such as cellular senescence, as well as cell-extrinsic, such as changes in the regenerative environment. Understanding how these mechanisms impact on regenerative processes is essential to devise therapeutic approaches to improve tissue regeneration and extend healthspan. This review offers an overview of how regenerative abilities change through lifespan in various organisms, the factors that underlie such changes and the avenues for therapeutic intervention. It focuses on established models of mammalian regeneration as well as on models in which regenerative abilities do not decline with age, as these can deliver valuable insights for our understanding of the interplay between regeneration and aging.

Molecular pathology endpoints useful for aging studies

“…This leads to a decline in regenerative capacity and the ability to maintain tissue homeostasis (Yun, 2015). Prolonged caloric restriction attenuates this age-related decline in cell proliferation (Li et al, 1997; Wolf et al, 1995).…”

Prospective purification and characterization of Müller glia in the mouse retina regeneration assay

“…Interestingly, regeneration of the damaged chicken retina is less limited than regeneration in mammals: low numbers of amacrine, bipolar, and ganglion cells can be de novo generated but, as in mammals, this potential becomes reduced with increasing age (Fischer, McGuire, Dierks, & Reh, 2002;Fischer & Reh, 2003). It is well known from regeneration in other organs and species that regulated mechanisms might restrict regeneration in mature or old cells (Yun, 2015). In summary, previous work on zebrafish, chicken, and rodent retina regeneration has discovered various signaling mechanisms involved in, necessary for, and/or sufficient for regeneration (Bermingham-McDonogh et al, 2012;Goldman, 2014;Gorsuch & Hyde, 2014;Lenkowski & Raymond, 2014).…”

Unhealthy Stem Cells: When Health Conditions Upset Stem Cell Properties

“…Aging is the most common studied health condition that directly affects the properties of stem cells [67]. Aging is a complex process that represents the accumulation of changes over time in an organism.…”

“…Although not a degenerative disease per se, the continuous cell and tissue changes throughout life make it similar to degenerative processes. The life-long persistence of stem cells makes them vulnerable to the accumulation of cellular damage, which can lead to senescence, loss of regenerative function or even to cell death [67]. Many tissues show a decrease in the ASC population with age, as well as proliferative dysregulation and a decline in functional capacity [68].…”