August 17, 2016 at 12:33AM

Today I Learned: 1) Today is day 1 of the Rejuvination Biotechnology 2016 conference, so I have a bunch of aging-research-related facts for your perusal. I'll start with senescent cells. Senescence is a state that many different kinds of cells can flip to permanently, and it's associated with three coupled phenotypes -- senescent cells are highly resistant to apoptosis and in general rather resistant to death; senescent cells don't replicate; and senescent cells secrete a complex (but consistent) mix of proteins, hormones, and other factors. Senescence seems to do a few things, some of which are good and some of which are bad. Good thing #1: It's a dead-end for an otherwise pre-cancerous cell. Senescence is thought to be one of the mechanisms by which a cell can prevent itself from going cancerous, presumably if the normal apoptotic pathways break somehow. Good thing #2: Senescent cells increase inflammation locally, and seem to be important for promoting normal, effective wound healing. When you lacerate a mouse, a bunch of cells in the region of the wound turn senescent, which appears to recruit a bunch of machinery to repair the wound. Once the wound is healed, most of the senescent cells get eaten up by the innate immune system. Bad thing: Senescent cells increase inflammation locally, and seem to be highly stressful and possibly carcinogenic when they stick around chronically (for decades). When a wound is healed, *some* of the senescent cells in the area tend to survive, and they basically never, ever go away. They also never stop secreting all those inflammatory factors, which is pretty hard on your body if you accumulate too many senescent cells. Today I learned that one possible reason some senescent cells survive is that they secrete a lot of proteases (enzymes that break down proteins). There's variation in how much protease each senescent cell produces, and it turns out that the ones that survive cleanup by the innate immune system tend to be the ones that secrete a ton of protease. It sounds to me like all that secreted protease is digesting one of the factors the immune system uses to recognize senescent cells. This protease secretion may also be what makes senescent cells carcinogenic, or at least makes cancers worse -- all that protease eats at surrounding extracellular matrix, which makes cancerous cells more likely to slough off and metastasize. 2) There have been a ton of studies on C. elegans (an almost-microscopic soil worm) showing that some compound or another dramatically increases their lifespan. Usually, these make big news, and are quickly followed up by a bunch of studies which fail to replicate the findings. Why? A joint team from the Buck Institute for Research on Aging, Southampton University, and UC Davis ran a cross-lab comparison study to try to figure out what was going on. Along the way, they found some compounds that look like they really do reliably increase C. elegans lifespan, but the part I found really interesting was the control experiment. One of the key points of the study was to figure out just how much variation there is in C. elegans lifespan experiments, and where the variability comes from. To do this, the teams came up with a joint, carefully planned-out protocol, trying to nail down every possible variable down to the lot numbers of their equipment and reagents. The three labs then ran simple longevity experiments on a bunch of different strains of three different worm species -- they grew the worms on a plate full of bacteria, and watched to see how long the worms lasted. Unsurprisingly, there was a lot of variation in worm lifespan. Surprisingly, there was *almost no* variation across labs -- roughly 0% of the variation could be explained by intra-lab differences. There were certainly differences between strains of worm, and even bigger differences between species, but the single biggest source of variance (by about a factor of 2) was *experimental replicates*. Sometimes, you would culture a plate of worms and the whole plate would live a really long time. Other times, you would put in a seemingly-identical plate of worms in the incubator and they would all die relatively quickly. This was consistent across the three different labs, and it actually seemed to follow a *bimodal* pattern -- lifespans weren't just random, they would tend to either all be high or all be low, depending on the plate, but not in a predictable way. Exactly where that variance was coming from isn't clear, but it *does* sound like a likely explanation for the fiascos over stuff like sirtuins -- the initial experiments showing effects of the drug happened to grow a bunch of short-lived plates for their controls, and a bunch of long-lived plates for their drug-treated condition. You can read more here (open access!): http://ift.tt/2aY5vcc 3) The Wake Forest Institute for Regenerative Medicine can reproduce decent facsimiles of mammalian follicles in vitro (that's the kind of follicle that produces eggs, not the kind that produces hair). They extract cells from an ovary, then culture those cells on a plate with tons of tiny little inverted-pyramid-shaped wells, which causes the cells to form clumps. Those clumps look an awful lot like follicles, and they behave a bit like them, too -- they can secrete estrogen and progesterone more-or-less stably (with more-or-less the right dynamics), and they can produce egg cells that can be fertilized (though it's still up in the air whether those fertilized eggs can be implanted successfully). 4) Speaking of culturing mini-organs, did you know you can produce milk in a culture dish? Apparently it's not *that* difficult to grow mammary cells in a slightly structured way that lets them produce milk in vitro. Also, if you add senescent cells to the culture, it disrupts their structure and kill milk production.... 5) There was an interesting idea from the MIT Economics department about how to fund expensive medical treatments. One of the huge problems with bringing preventative anti-aging treatments to market is that they're not necessarily good money, and there might not be a good way to pay for them if they're too expensive, even if they would end up saving money in the long run. One idea for how to better finance expensive medical treatments is to provide a medical loan to the patient -- whoever makes the treatment pays for the treatment, and then as long as the patient remains healthy, they pay back the producer in regular, small installments. It still costs money, but it means the patient doesn't get hit with an impossible-to-pay bill (or get outright refused), and it provides good incentive to the producer to make sure the treatment works. 6) Speaking of MIT, but otherwise completely unrelated to regenerative medicine, Duoskin tattoos! MIT media lab and Microsoft have teamed up to bring wearable electronic tattoos to the world. The tattoos are made of printed gold and silver leaf, and can be worn on any skin surface. So far they've demonstrated a touch pad/scrollpad, a small LED-like color-changing display (a few pixels by a few pixels), and a wireless communication circuit a la RFID tags. More at http://ift.tt/2bguLyI Thanks for cluing me in on this, Sarah Seid!