{"id":89,"date":"2013-03-25T02:14:15","date_gmt":"2013-03-25T02:14:15","guid":{"rendered":"http:\/\/joshmitteldorf.peachpuff-wolverine-566518.hostingersite.com\/?p=89"},"modified":"2013-03-25T03:06:08","modified_gmt":"2013-03-25T03:06:08","slug":"young-blood","status":"publish","type":"post","link":"https:\/\/scienceblog.com\/joshmitteldorf\/2013\/03\/25\/young-blood\/","title":{"rendered":"Young Blood"},"content":{"rendered":"

Dr.\u00a0 Harold Katcher of the University of Maryland believes that signals in our blood tell our stem cells how old to act, and that some key disabilities of old age might be reversed by serial transfusions of blood plasma from a young donor.\u00a0 Plasma transfusion is a routine medical procedure, established to be safe for humans, but remarkably, its potential for rejuvenation has never been tested in humans or even in animals.<\/em><\/p>\n

In a 2005 experiment<\/a> that would make anyone with the least\u00a0sensitivity to animal welfare cringe, Irina and Michael Conboy of UC\u00a0Berkeley surgically joined pairs of mice so that they shared a common\u00a0blood supply.\u00a0 One old mouse and one young mouse became artificial\u00a0Siamese twins.\u00a0 For control, Conboy also paired two old mice and two\u00a0young mice.<\/p>\n

\"\"<\/p>\n

After the surgery, they injured one mouse from each pair, and\u00a0monitored the healing process at a cellular level.\u00a0 As expected, the\u00a0young mice recovered from injury much more efficiently than old mice.\u00a0The surprise was that old mice that were paired with young mice healed as if they were young. \u00a0\u201cImportantly, the enhanced regeneration of aged muscle was due\u00a0almost exclusively to the activation of resident, aged progenitor\u00a0cells, not to the engraftment of circulating progenitor cells from\u00a0the young partner.<\/em>\u201d In other words, it was not young cells\u00a0that implanted themselves in the old mice; it was signal\u00a0proteins<\/i> in the blood that told the old mouse tissue to go\u00a0ahead and heal as if it were young.\u00a0 Something in the young blood was\u00a0signaling the satellite cells of the old mice to divide and grow\u00a0efficiently, as if they were young.<\/p>\n

The Conboys went on from muscle cells to study the livers of their\u00a0test animals.\u00a0 The liver is constantly regenerating, and in livers of\u00a0old animals this regrowth slows way down. \u00a0They found that livers of\u00a0old mice exposed to young blood had rejuvenated potential for growth.<\/p>\n

 <\/p>\n

Some background<\/strong><\/p>\n

Satellite cells<\/a> are\u00a0partially-differentiated stem cells.\u00a0 A pluripotent stem cell can\u00a0produce daughter cells capable of taking on any role in the body –\u00a0nerve, muscle, bone, blood, etc.\u00a0 At the other extreme, the\u00a0terminally differentiated cells of the body perform their functions but never divide to create new cells.\u00a0 A satellite cell is an in\u00a0between stage.\u00a0 It is derived from a pluripotent stem cell, and its\u00a0job is to divide and create a supply of new muscle cells only.\u00a0 The\u00a0Conboys found that satellite cells from older mice were rejuvenated\u00a0by exposure to blood from the young mouse. \u00a0Blood is best known as white and red corpuscles, but the fluid\u00a0(plasma) is important as well.\u00a0 Blood plasma contains dissolved\u00a0hormones, tiny quantities of powerful signal proteins.\u00a0 One class of signal molecules effects\u00a0notch signaling<\/a>.<\/p>\n

Notch signaling is a mechanism by which cells can respond to external\u00a0signals without allowing the signal molecule to enter the cell.\u00a0 It\u2019s\u00a0a lock-and-key mechanism where the key inserted from outside controls\u00a0a latch inside the house.\u00a0 There are four types of notch proteins,\u00a0which span the cell membrane, head in the cell and tail extending\u00a0outside.\u00a0 The tail contains a receptor for specific signal molecules,\u00a0and when one of these finds its way to the receptor, the entire\u00a0molecule changes conformation along its length, reconfiguring the\u00a0head which is inside the cell.\u00a0 The Conboy study identified a notch\u00a0signal molecule called Delta that was present in the young mouse\u00a0blood, but missing in older mice.\u00a0 Responding to the Delta signal,\u00a0old satellite cells were reprogrammed to act young.<\/p>\n

(In case you don’t find this to be bizarre, go back and read it again. \u00a0Old cells become dysfunctional not because there’s something wrong that can’t be repaired. \u00a0All they need is a messenger protein commanding them to Be Young!)<\/p>\n

 <\/p>\n

From mouse to human<\/strong><\/p>\n

The Conboys with colleague Morgan Carlson<\/a>\u00a0went on to explore the biology of aging stem cells in humans.\u00a0 After a disappointing\u00a0response to their ad seeking young volunteers to be surgically joined\u00a0to genetically-matched old fogeys, they wisely decided to work instead with\u00a0cell cultures.\u00a0 They were able to rejuvenate old, inactive stem cells\u00a0by treatment with young blood plasma.\u00a0 They identified another notch\u00a0signal protein that make this happen: TGF-\u03b2 (\u201cT<\/strong>ransforming G<\/strong>rowth F<\/strong>actor\u201d). \u00a0Using TGF-\u03b2, cells drawn from a 70-year-old human were made to behave and function like\u00a0cells from a 20-year-old.<\/p>\n

 <\/p>\n

Katcher\u2019s Proposal<\/strong><\/p>\n

Katcher\u2019s new paper<\/a> presents a lot of background<\/p>\n