Heterochronic parabiosis for the study of the effects of aging on stem cells and their niches

Abstract

Aging is unmistakable and undeniable in mammals. Interestingly, mice develop cataracts, muscle atrophy, osteoporosis, obesity, diabetes and cognitive deficits after just 2-3 postnatal years, while it takes seven or more decades for the same age-specific phenotypes to develop in humans. Thus, chronological age corresponds differently with biological age in metazoan species and although many theories exist, we do not understand what controls the rate of mammalian aging. One interesting idea is that species-specific rate of aging represents a ratio of tissue attrition to tissue regeneration. Furthermore, current findings suggest that the age-imposed biochemical changes in the niches of tissue stem cells inhibit performance of this regenerative pool, which leads to the decline of tissue maintenance and repair. If true, slowing down stem cell and niche aging, thereby promoting tissue regeneration, could slow down the process of tissue and organismal aging. In this regard, recent studies of heterochronic parabiosis provide important clues as to the mechanisms of stem cell aging and suggest novel strategies for enhancing tissue repair in the old. Here we review current literature on the relationship between the vigor of tissue stem cells and the process of aging, with an emphasis on the rejuvenation of old tissues by the extrinsic modifications of stem cell niches.

Combined associations of body weight and lifestyle factors with all cause and cause specific mortality in men and women: prospective cohort study

“…29 30 These factors can accelerate the accumulation of unrepaired molecular damage and senescent cells, stimulate the DNA damage response, inhibit stem cell regenerative function, and promote involuntary weight loss, organ dysfunction, and frailty 710 31 32 33…”

Sirt1-Independent Rescue of Muscle Regeneration by Resveratrol in Type I Diabetes

“…Muscle stem cells (also known as satellite cells) are typically quiescent and start dividing in response to injury or attrition of muscle fibers (myofibers); activated satellite cells then differentiate along the myogenic lineage into fusion-competent proliferating myoblasts (expressing Pax7, MyoD and desmin) and postmitotic multinucleated myotubes (expressing eMyHC), which repair the damaged tissue [19]. Based on our work, type I diabetes has a direct negative effect on the ability of muscle stem cells to activate and regenerate muscle, due to intensified myostatin/ TGF-β receptor/pSmad 3 signaling [3].…”

Meeting current musculoskeletal health demand through deeper insights into tissue homeostasis and regeneration

“…Results obtained after heterochronic parabiosis, that is, exposure of an aged organism to a youthful systemic environment, show that failed healing could be attributed not to the stem cells but to the aging process [10]. Identifying systemic differences between old and young may help in achieving molecular control over the niche composition and adequate stem cell activation.…”

“…Recent research in rejuvenation indicated that the age of the host dictates the success of the approach [10]. The failure of triggering regenerative mechanisms is not attributed to the stem cells but to an old niche, that is, the environment that regulates cell fate.…”

“…Recent data indicate that the niche can be revitalized by administration of determined molecular signals. For example, calibration of Notch, Wnt and TGF-b/Smad signaling pathways recovers the deficiency of repair of old muscle [10].…”