Senescence and Ageing

An impressive review in thus week's NATURE surveys the complexities of the causes and mechanisms of cellular senescence. Of particular interest is the increasing evidence for  a critical role of senescent cells in the aging of tissues and organs. This can come about in many ways including loss of stem cell capabilities. However, one key aspect is the ability of senescent cells to produce inflammatory factors that then lead to tissue degeneration.  The growing information on the link between cell senescence and aging opens the door to  possible therapeutic approaches that might slow down the decline of functions with age. 

http://www.nature.com/nature/journal/v509/n7501/full/nature13193.html 

NIH Bows to Political Correctness

The NIH has long sought to ensure that the diagnostic and therapeutic research it supports will be of value to both men and women.  For that reason it has emphasized steps such as full inclusion of females in clinical trials. Now however, new policies are broadening that mandate to an unreasonable degree.  Not only will scientists be asked to include females in clinical trials and in more basic studies using animal models of disease, but they will also be asked to use cell lines derived from both males and females (1).

NIH policies to encourage full representation of females in clinical trials and use of female animals in basic research are sensible and laudable. But extending that policy to cell lines- ridiculous! Most cell lines used in basic research laboratories have been in culture for decades. They are so far removed from the original tissue cells that their responses to drugs or other stimuli are vastly different—this being a major problem for drug development. Insisting on equal representation of male and female cells in basic research is political correctness run amok!!

(1) http://www.nature.com/news/policy-nih-to-balance-sex-in-cell-and-animal-studies-1.15195 

Young Blood for Ageing Organs

There has been a great deal of interest in the idea of using stem cells to reverse age-associated declines in organ function. However, recent studies have shown that ageing tissues often have plenty of stem cells; nonetheless, the stem cells lose their ability to differentiate and to repopulate tissues with healthy cells. Now, in recent issues of SCIENCE (1) and NATURE MEDICINE (2), several research reports have shown that factors in the blood of young mice can reverse age-related declines in stem cell and tissue function. Some of these studies used parabiosis, that is joining the circulatory systems of old and young animals. Another study focused on GDF11, a TGF-beta type growth factor whose expression declines in older animals. Injections of this protein improved both muscle function and (in another report) growth of brain blood vessels and olfactory neurons. Perhaps the most exciting study (2) demonstrated that blood from young mice could reverse age-related declines in hippocampal cells and associated cognitive impairments.

There has always been tremendous interest in seeking means to slow the declines associated with ageing. However, the work discussed here, as well as other recent studies, suggest that an actual reversal (at least in part) of the ageing process may be possible. While this is all still far away from use in humans, it offers a tantalizing prospect that could have enormous implications both medically and in terms of impacts on society. 

(1)

http://www.sciencemag.org/content/344/6184/570.full 

(2) 

http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.3569.html

Finally, some sound thoughts about PhD training from the big shots!

PNAS recently published an opinion article from four very prominent individuals about the current malaise in biomedical research and training.  The authors were Bruce Alberts (former editor of SCIENCE), Marc Kirschner (a Dept Chair at Harvard), Shirley Tilghman (former President of Princeton) and Harold Varmus (nobelist, and Director of the National Cancer Institute). This is about as high powered as you can get in science!

The article analyzed several problematic aspects of the current biomedical research system but prominently featured the depressing scenario regarding PhD training. Based on various perverse incentives, both senior faculty and university administrators have continued to expand the PhD trainee population during a period when employment prospects for biomedical PhDs have drastically diminished. Academia is at saturation, the pharmaceutical industry is eviscerating its research programs, and the growth of smaller biotech companies is just not enough to provide adequate jobs. In my experience more and more PhDs are going into jobs such as clinical trials management, market research, and other administrative functions for which intensive training in laboratory research is not essential. What a waste!

The abovementioned gurus make some valuable suggestions such as:

(1)   Removing support for graduate stipends from research grants and placing them in competitive training grants; this would give NIH more direct control over trainee numbers.

(2)   Placing renewed emphasis on Master’s degrees. In many cases this would provide sufficient science training for some of the jobs mentioned above, while consuming far less time for the trainee.

(3)   Developing stable career paths for staff scientists (as opposed to faculty/principle investigators) in universities and other research institutions. There are lots of talented people who would like to do science but do not want the pressure of constantly seeking grant funding. There should be ways of supporting these individuals.

None of these ideas are new. Many people, including me, have been advocating similar changes for years. However, it is nice to see some very influential people espouse the same ideas. Maybe something will get done about the problem. But don’t hold your breath!

http://www.pnas.org/content/111/16/5773.long