The average life expectancy currently increases at a rate of more than one year every decade. This dramatic demographic change poses economic challenges, but also provides new opportunities. The opportunities for biological research institutions are to explore the exciting biology of aging, with the future possibility that basic principles revealed by this exploration will result in treatments and interventions that delay the aging process and lead to healthier aging.
Aging is associated with a striking increase in a wide range of age-dependent diseases, including neurodegenerative diseases, diabetes, and cancer. Even in the absence of diseases, aging is accompanied by the decline of a number of physiological functions, for example a decline in muscle strength and in cognitive function. Fundamental questions arise: is age-dependent decline inevitable? Is there some plasticity to the aging process?
For many decades, aging was not considered to be a regulated process, and just thought to be the by-product of wear-and-tear. But this view has changed, and it is now clear that aging is a plastic process, regulated by a combination of environmental and genetic factors. Importantly, studies in model organisms (yeast, worm, flies, and mice) and in humans have unraveled a series of crucial genes and pathways that are implicated in a conserved manner in regulating longevity. Variations in such genes can extend lifespan by 2-3 fold in lower organisms, and by more than 50% in mammals.
Aging and stem cells
Key aspects of mammalian tissue aging may be attributable to a loss of regenerative capacity of adult stem cells. Unlike differentiated cells, adult tissue-specific stem cells retain a portion of the plasticity of their embryonic counterparts and can differentiate into specific cell types. Adult stem cells have now been identified in most adult tissues in mammals, including the highly regenerative blood, intestine, and skin, as well as the less regenerative skeletal and cardiac muscle and brain. Adult tissue stem cells play important roles in overall tissue homeostasis, repair in response to injury, and in the adaptive nature of the tissue. For example, in the nervous system, adult stem cells are important for adult learning and the formation of new memories.
Throughout the course of organismal lifespan, adult stem cells face the challenge of maintaining an undifferentiated, yet committed state that is primed to respond to the environment. Adult stem cells are subject to the environmental stresses and intracellular damages that accompany the aging process. A fundamental question is whether stem cells progressively lose their potential to self-renew and properly differentiate during organismal aging, and if so, what are the molecular mechanisms underlying this decline. Are age-dependent defects to stem cells reversible?
Understanding the mechanisms by which stem cells and tissue regeneration are affected during aging will give pivotal insights into ways to delay age-dependent decline. Tapping into the regenerative potential of dormant endogenous adult stem cells will likely be a promising avenue to prevent and treat a number of age-dependent diseases characterized by tissue degeneration. The recent ability to generate in vitro pluripotent stem cells from adult patients has opened exciting new paths for exogenous stem cell therapies to treat age-dependent diseases. Understanding how age influences stem cell properties will be critical in implementing new therapies and in promoting healthy aging.