Rapamycin for aging stem cells

in physiological function and reserve [1]. Hallmarks of aging include cellular senescence, stem cell exhaustion, DNA damage, telomere attrition, and deregulated nutrient sensing among others [1]. Age-associated stem cell dysfunction has been well characterized in various tissue specific stem cell populations [2] leading to a decline in regenerative potential of tissues. Some stem cell populations have been found to increase in number with age (hematopoietic stem cells for example), while many others such as neural stem cells and muscle progenitor cells deplete with age whereby stem cell pools become exhausted leading to reduced regeneration/repair capacity of tissue [1, 2]. However, stem cell dysfunction due to cell intrinsic factors (DNA damage, oxidative stress, and mitochondrial dysfunction) along with extrinsic factors (chronic inflammation, changes in niche) is a hallmark of aging. It turns out that mTOR (mammalian target of rapamycin) plays a significant role in stem cell dysfunction through various mechanisms highlighting its potential as an anti-aging target to rejuvenate stem cell function. In fact, mTOR regulates many of the hallmarks of aging. A breakthrough study in 2009 by Harrison et al. showing the lifespan extending properties of rapamycin in genetically heterogenous mice led to significant study of rapamycin as an antiaging intervention. Since that time, rapamycin has been well studied in aging and age-related functional decline mainly through the modulation of autophagy, mitochondrial function, insulin signaling, and senescence [3].