Regeneration, Rejuvenation, and Replacement: Turning Back the Clock on Tissue Aging

Abstract

While some animals, such as planaria and hydra, appear to be capable of seemingly endless cycles of regeneration, most animals experience a gradual decline in fitness and ultimately die. The progressive loss of cell and tissue function, leading to senescence and death, is generally referred to as aging. Adult ("tissue") stem cells maintain tissue homeostasis and facilitate repair; however, age-related changes in stem cell function over time are major contributors to loss of organ function or disease in older individuals. Therefore, considerable effort is being invested in restoring stem cell function to counter degenerative diseases and age-related tissue dysfunction. Here, we will review strategies that could be used to restore stem cell function, including the use of environmental interventions, such as diet and exercise, heterochronic approaches, and cellular reprogramming. Maintaining optimal stem cell function and tissue homeostasis into late life will likely extend the amount of time older adults are able to be independent and lead healthy lives.

Figure 1.

Effects of aging on adult stem cells. Adult stem cells reside within a niche that provides critical signals for maintenance, proliferation, and survival. Stem cells can divide to self-renew and produce progeny that will differentiate along a specific lineage. Aging can lead to a loss of tissue homeostasis when stem cells (A) lose the ability to self-renew, leading to depletion of the stem cells pool, (B) do not divide as often, thereby generating fewer progenitor cells, that may also be impaired, (C) become unable to respond to signals from the niche that lead to “activation” and proliferation, (D) become senescent and no longer divide, and/or (E) die or undergo programmed cell death. Reviewed in Jones and Rando (2011). (Figure created with BioRender.com.)

Figure 2.

Approaches to rejuvenate endogenous stem cell pools. Several approaches have been used to activate or rejuvenate endogenous stem cell pools to counter age-related changes in tissue function. (A) Dietary interventions, including dietary restriction (DR) or fasting, (B) nonstrenuous exercise, (C) heterochronic exchange of blood, plasma, or cells, and (D) reprogramming using “Yamanaka factors” to counter epigenetic changes associated with aging. (Figure created with BioRender.com.)