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Barzilai N.,Yeshiva University | Guarente L.,Massachusetts Institute of Technology | Kirkwood T.B.L.,Vitality | Partridge L.,Vitality | And 5 more authors.
Nature Reviews Genetics | Year: 2012

Rapidly increasing numbers of older people present many countries with growing social and economic challenges. Yet despite the far-reaching implications of ageing, its biological basis remains a topic of much debate. Recent advances in genomics have spurred research on ageing and lifespan in human populations, adding to extensive genetic studies being carried out in model organisms. But how far is ageing controlled by our genes? In this Viewpoint, six experts present their opinions and comment on future directions in ageing research. © 2012 Macmillan Publishers Limited. All rights reserved.


Eggel A.,University of Bern | Wyss-Coray T.,Stanford University | Wyss-Coray T.,Center for Tissue Regeneration
Swiss Medical Weekly | Year: 2014

Modern medicine wields the power to treat large numbers of diseases and injuries most of us would have died from just a hundred years ago, yet many of the most devastating diseases of our time are still untreatable. Chronic conditions of age such as cardiovascular disease, diabetes, osteoarthritis or Alzheimer's disease turn out to be of a complexity that may require transformative ideas and paradigms to understand and treat them. Parabiosis, which is characterised by a shared blood supply between two surgically connected animals, may just provide such a transformative experimental paradigm. Although forgotten and shunned now in many countries, it has contributed to major breakthroughs in tumour biology, endocrinology and transplantation research in the past century. Interestingly, recent studies from the United States and Britain are reporting stunning advances in stem cell biology and tissue regeneration using parabiosis between young and old mice, indicating a possible revival of this paradigm. We review here briefly the history of parabiosis and discuss its utility to study physiological and pathophysiological processes. We argue that parabiosis is a technique that should enjoy wider acceptance and application, and that policies should be revisited to allow its use in biomedical research.


Kirby E.D.,Stanford University | Kuwahara A.A.,Stanford University | Messer R.L.,Stanford University | Wyss-Coray T.,Stanford University | Wyss-Coray T.,Center for Tissue Regeneration
Proceedings of the National Academy of Sciences of the United States of America | Year: 2015

The adult hippocampus hosts a population of neural stem and progenitor cells (NSPCs) that proliferates throughout the mammalian life span. To date, the new neurons derived from NSPCs have been the primary measure of their functional relevance. However, recent studies show that undifferentiated cells may shape their environment through secreted growth factors. Whether endogenous adult NSPCs secrete functionally relevant growth factors remains unclear. We show that adult hippocampal NSPCs secrete surprisingly large quantities of the essential growth factor VEGF in vitro and in vivo. This self-derived VEGF is functionally relevant for maintaining the neurogenic niche as inducible, NSPC-specific loss of VEGF results in impaired stem cell maintenance despite the presence of VEGF produced from other niche cell types. These findings reveal adult hippocampal NSPCs as an unanticipated source of an essential growth factor and imply an exciting functional role for adult brain NSPCs as secretory cells.


Villeda S.A.,Stanford University | Wyss-Coray T.,Stanford University | Wyss-Coray T.,Center for Tissue Regeneration
Autoimmunity Reviews | Year: 2013

The ability of the adult brain to generate newly born neurons dramatically declines during aging, and has even been proposed to contribute, in part, to age-related cognitive impairments. While intrinsic molecular mechanisms underlying decreased neurogenesis during aging have begun to be elucidated, relatively little is still known as to the contribution of the systemic environment. Interestingly, immune signaling has quickly emerged as a key negative regulator of adult neurogenesis, and has more recently been functionally linked to the aging circulatory systemic environment. In this review we examine the role of the aging systemic environment in regulating adult neurogenesis and cognitive function. We discuss recent work from our group using the aging model of heterochronic parabiosis - in which the circulatory system of two animals is connected - to highlight the contribution of circulatory immune factors to age-related impairments in adult neurogenesis and associated cognitive processes. Finally, we propose the possibility of combating brain aging by tapping into the 'rejuvenating' potential inherent in a young circulatory systemic environment. © 2012.


Mosher K.I.,Stanford University | Wyss-Coray T.,Stanford University | Wyss-Coray T.,Center for Tissue Regeneration
Biochemical Pharmacology | Year: 2014

Microglia, the immune cells of the central nervous system, have long been a subject of study in the Alzheimer's disease (AD) field due to their dramatic responses to the pathophysiology of the disease. With several large-scale genetic studies in the past year implicating microglial molecules in AD, the potential significance of these cells has become more prominent than ever before. As a disease that is tightly linked to aging, it is perhaps not entirely surprising that microglia of the AD brain share some phenotypes with aging microglia. Yet the relative impacts of both conditions on microglia are less frequently considered in concert. Furthermore, microglial "activation" and "neuroinflammation" are commonly analyzed in studies of neurodegeneration but are somewhat ill-defined concepts that in fact encompass multiple cellular processes. In this review, we have enumerated six distinct functions of microglia and discuss the specific effects of both aging and AD. By calling attention to the commonalities of these two states, we hope to inspire new approaches for dissecting microglial mechanisms.

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