A recent article in MIT Technology Review is entitled "Why 'reprogramming' is the buzziest approach to reversing aging right now." It starts out by correctly discussing previous dead ends in rejuvenation research, attempts to slow or reverse aging. Then the article goes into hype mode, trying to promote something called "cellular reprogramming." The article claims this:
"Some promising studies in mice suggest that this approach might help wind back the clock. It seems to improve tissue healing, restore vision, and even improve learning and memory."
We are told that billions are being invested into startups trying to do this "cellular reprogramming," and a mention is made of three startups that are not publicly traded (Altos Labs, Retro Biosciences and NewLimit) We are told that billionaires are pouring lots of money into these startups.
The link above for the phrase "improve learning and memory" takes you to the paper "Cognitive rejuvenation through partial reprogramming of engram cells." Let me explain why that paper is a low-quality paper that fails to provide any decent evidence for any such thing as "cognitive rejuvenation." The paper claims to have improved memory in mice, but does not publish any robust evidence to support such a claim.
The first reason the paper is not a high-quality study is its failure to use large enough study group sizes. You should not get the wrong idea when the paper refers to using 39 mice. Those mice were divided into various different study groups, leaving too-small study group sizes such as a study group size of only 7 mice and a study group size of only 15 mice, a study group size of only 11 mice, a study group size of only 12 mice, and a study group size of only 5 mice. No paper like this should be taken seriously unless all of its study groups were at least 15 to 20 animals per study group. Almost always the study group sizes needed for reliable results in neuroscience experiments of this types are sizes of 20 animals or greater.
The second reason the paper is a low-quality study is that it used poor methods to test memory in the mice it used. The first type of method used was the utterly unreliable method of trying to judge "freezing behavior" in mice. My post here explains at great length why this method is utterly unreliable as a technique for testing memory performance. That post is entitled "All Papers Relying on Rodent 'Freezing Behavior' Estimations Are Junk Science."
When "freezing behavior" estimations go on, things typically work like this. A rodent will be trained to fear some thing such as a shock plate that gives the rodent a shock when the rodent steps on it. Then later the rodent will be placed in a cage that includes the fear stimulus such as the shock plate. The researchers will attempt to record what percentage of some time (say, a minute or 3 minutes) that the rodent was immobile when placed in such a case. This will be called a "freezing percentage," and will be claimed as a measure of how well the rodent remembered the fear stimulus.
The technique makes no sense. In the real world, rodents don't usually freeze and become immobile when they are afraid. They are much more likely to flee. So trying to judge recall of a fearful stimulus by judging how much time a rodent was immobile in a cage makes no sense as a measuring method. The thing that utterly destroys the credibility of all "freezing behavior" graphs is that they can be produced in any of more than a dozen ways. A researcher can put a rodent in the cage for three minutes and graph the whole three minutes. Or he can graph only the first 30 seconds, or only the first minute, or only the first two minutes. In each ten seconds of such a three minutes, the researcher can count it as "moving" if the rodent moves one second during that period; or the researcher can count two seconds of movement as being mobility; or the researcher can use three seconds, or four seconds, or five seconds.
There are no prevailing standards for how "freezing behavior" is judged. With there being a dozen different possibilities of how "freezing behavior" can be judged and graphed, with each having a possibility of success of about 50%, it will be almost certain that the researcher will be able to choose some analysis method that will show the desired difference in "freezing behavior," even if the memory intervention being tested had no real effect. This is a large part of the reason why "freezing behavior" judgments are worthless as evidence for an increase or decrease in memory in rodents. Such "freezing behavior" judgments are very common in neuroscience research, but that is just another indication of the very sick state of today's neuroscience research, where there prevails a wide variety of pathologies.
Here is the "freezing behavior" graph from Figure 1 of the paper "Cognitive rejuvenation through partial reprogramming of engram cells." Its appearance matches closely the general appearance of a junk science "freezing behavior" graph as I outlined it in the diagram above that I made months before reading this paper.
We have three indications here of utterly unconvincing results and junk science:
(1) A use is made of the "freezing behavior" method which is an utterly unreliable method, for the reasons discussed above.
(2) Failing to follow principles of good science, the authors have failed to even list in their graph what span of time was used to judge this alleged "freezing behavior."
(3) The study group sizes used were too small for any reliable result to be claimed. You can tell the study group sizes here by counting up the number of circles behind each of the bars. Each circle represents one mouse. The graph showed that the study group sizes were only 12 mice per study group. An adequate study group size would have required at least 15 or 20 mice per study group.
The authors of the paper also used another technique to try to measure memory performance. That technique was the widely used Morris water maze test (MWM). The Morris Water Maze test can be a fairly reliable way of measuring recall in rats, if the test is used in a straightforward way. The water maze consists of a circular open tank rather like a child's bathing tub, deeper than a rodent's length, with a hidden platform on one side of the tank, about an inch or two below the water surface. The tank is filled with a milk-colored white fluid, typically by pouring something in water to make it opaque.. A rodent is placed in the tub, and has to tread water to stay alive. Eventually the rodent will discover that by swimming to the hidden platform the rodent can comfortably rest, without having to tread water. You test the rodent's memory by exposing him to the water maze a certain number of times, until you find that the rodent immediately goes to the hidden platform. Then later the rodent's memory can be tested by putting the rodent in the same Morris Water Maze tank, and seeing whether it quickly swims to the platform.
The Morris Water Maze test (MWM) may be a fairly reliable technique for testing memory, when it is used with rats, in a straightforward way, with an adequate study group size. By "in a straightforward way," I mean doing something such as simply recording the time it took rats placed in the Morris Water Maze to reach the submerged platform. This time is called the "escape latency" time. When the Morris Water Maze test is done in a reliable way, we will see a simple bar graph comparing this "escape latency" time for two different groups, an experimental group and a control group. That "escape latency" is simply the average time it took a rat in the group to reach the submerged platform. The graph might look like the graph below. If the study group size was large enough, this might be good evidence that the experimental group was remembering better than the control group.
But there are many studies that use the Morris Water Maze test (MWM) in an objectionable way, doing analytics in a way that is not straightforward, in a way that smells like "keep torturing the data until it confesses." For example, we may see charts showing how much time rats spent in a particular quadrant of the Morris water maze. Or we may see charts plotting the exact path that particular rats traversed in the Morris Water Maze test. When data analysis this complicated and arbitrary starts going on, there then occurs a plummeting of the reliability the Morris Water Maze (MWM) as a test of memory. Whenever you are allowed to analyze data in very many different ways, you will be able to find some desired difference between a control group and an experimental group. Finding that difference will be as easy getting a desired "heads" flip of a coin when you are free to flip the coin a dozen times.
It is just that type of shortcoming that occurs in the paper "Cognitive rejuvenation through partial reprogramming of engram cells." We have some data showing results of experiments using the Morris Water Maze test (MWM). But the results do not include a single diagram like the one shown above. Instead we have convoluted analysis that smells like "keep torturing until it confesses." We fail to get any convincing simple and straightforward graph seeming to show superior memory in the rodents that supposedly underwent "cellular reprogramming." The study group sizes used in the Morris Water Maze test part of the paper are all lower than the minimum of 15 to 20 animals per study group that are required for decent statistical evidence.
There's another reason why the results of the Morris Water Maze test (MWM) in the paper "Cognitive rejuvenation through partial reprogramming of engram cells" are not convincing: the fact that in that paper the test was done with mice rather than rats. The Morris Water Maze test is not a reliable way to test memory when it is done with mice.
The result above is one that clearly tells us that the Morris Water Maze test (MWM) is simply not a reliable test of memory when it is performed on mice. It's a different story with rats, because with rats the test is more reliable.
So the truth is that the paper "Cognitive rejuvenation through partial reprogramming of engram cells" fails to provide any convincing evidence that its claimed "partial reprogramming" did any such thing as a memory improvement or a "cognitive rejuvenation" on the mice that were manipulated. The paper also fails to provide any decent evidence of any such thing as "engram cells" in the sense of cells storing memories. A groundless use of the phrase "engram cells" is epidemic in today's cognitive neuroscience. Neuroscientists are groundlessly applying that term to groups of cells, without doing anything to adequately justify the use of that term.
We now have a very ironic situation in which billionaires overflowing with cash are sometimes investing many millions or billions in a way that will probably be pretty much flushing money down the toilet. Such investments are based on "brains make minds" and "brains store memories" ideas that are incorrect. Such investments are being made by those eager to never have an earthly death. But when you adequately understand the many reasons why brains cannot possibly be the source of the human mind and cannot possibly be the storage place of human memories, and why each of us must be mentally something vastly more than any brain effects (reasons discussed in great detail in the posts of this blog and in 280+ posts and very many other posts of another blog of mine), you will tend to lose your fear of having an earthly death. Those very reasons are reasons telling us strongly that we are souls that will survive earthly death.
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