Commentary on FGF Signaling and Stem Cell Aging

You'll recall that researchers recently demonstrated that they could slow or reverse stem cell decline with age by manipulating FGF2 - in the satellite cell population that maintains muscle tissue, at least. Based on their work, the researchers proposed that stem cell aging involves issues with dormancy and recuperation. Because of certain changes in signaling in the supporting stem cell niche, stem cell populations in old muscles are not able to remain dormant sufficiently well to maintain their numbers and functionality.

Here is a commentary on this research, placing it into the context of other ongoing investigations into the causes of stem cell decline with aging and consequent loss of tissue integrity:

Gradual declines in tissue homeostasis, function, and regenerative ability are hallmarks of the aging process. Tissue-specific adult stem cells are the primary components of tissue regeneration and homeostasis. Therefore, an attractive theory to explain the age-associated decline in these processes centres around the effects of aging on stem cell function. The current debate focuses on the very nature of how stem cells age. Is the decline in stem cell function with age a cell autonomous change that happens due to the cumulative detrimental effects of DNA damage, epigenetic changes, or metabolic and mechanical stresses over time? Or is it an environmentally induced process whereby a perfectly functional stem cell is instructed to behave in a dysfunction manner by an aging niche or systemic milieu?

A recent [study] proposes a unique mechanism whereby a signal from the aged niche causes a cell autonomous and persistent change in the ability of a stem cell to maintain the quiescent state, which, over time, leads into impaired tissue regenerative capacity. ... aged satellite cells display an increased propensity to [leave quiescence, enter] the cell cycle and to undergo apoptotic cell death. ... What is particularly intriguing about environmental theories of stem cell aging is that they imply that the functional changes that occur in stem cells as they age are potentially reversible when the cells are placed in a 'young' environment.

This report also touches on another issue that is commonly debated: the role of stem cell number in the effects of aging on tissue function and regeneration. The reported effects of aging on stem cell number vary widely across different stem cell populations but also within the satellite cell literature. [The authors here] report reduced satellite cell numbers in aged animals and attribute that decline to the functional changes they describe: [increases] in cycling and cell death. They propose that functional changes of aged satellite cells, which have previously been shown to impair muscle regeneration, are further exacerbated by declining stem cell numbers. It will be interesting to determine if the maintenance of stem cell number can overcome their functional deficits to prevent an age-related decline in regenerative potential.



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