Tuesday, November 24, 2015

Young Blood Can Reverse Aging

The quest for stopping and even reversing the aging process has entered a new phase over the past few years. A few scientists have investigated the phenomenon of administering the blood of young mice to old mice, an experiment that has a long but not a very illustrious history. As far back as the 1600s renowned figures such Andreas Libavius and Robert Boyle (of Boyle’s Law fame) proposed that transfusions of the blood of the young might rejuvenate the old, but the experiment was a catastrophe since, at the time, there was no knowledge of blood groups. 

In recent years several scientists have returned to the experiment. In 2005 Conboy et al published a paper in Nature (1) in which they used a procedure called parabiosis where they surgically combined the circulatory systems of young and old mice. Together with a later study, (2) they found that the exposure of old mice to young blood restored proliferation and the regenerative capacity of satellite cells (skeletal muscle stem cells) as well as hepatocytes (liver cells) by re-activating molecular signaling. In 2011 Villeda et al (3) demonstrated that young blood can increase regeneration of brain cells in old mice and that old blood can inhibit regeneration in young mice. This and later studies (4) showed that certain proteins in old blood decrease regeneration of brain cells in young mice and impair cognition. Specifically, they found that beta-2 microglobulin is elevated in the blood of old mice and if injected systemically, or locally in the hippocampus, impairs cognitive function and neurogenesis in young mice. The same group (5) further showed that injecting plasma of young mice into old mice can increase regeneration of cells in the hippocampus and increase cognitive function.

It is known that TGF-b1, a multi-functional cytokine, becomes elevated with age in several organs, including muscle and brain (6). Hanadie et al. (7) demonstrated that TGF-b-1 inhibition enhances neurogenesis and muscle regeneration in old mice, as well as decreasing inflammation. Sinha et al. (8) published results showing that increasing GDF-11 levels in aged mice causes increased genomic integrity of muscle stem cells and restores the structure and function of muscle cells and brain (9), though the effects of GDF-11 have recently been challenged (10). In yet another study (11), researchers found that, unlike previous theories, mitochondrial DNA is not degraded in older mice and by changing the regulation of two genes, CGAT and SHMT2, that control glycine production, they could restore mitochondrial function in fibroblast cell lines to that of young cells.

Whatever the specific molecules turn out to be, and there will eventually be several, the exciting point of all these findings is that there are elevated levels of substances in the plasma of old mice that inhibit stem cells in various organs studied, and there are other substances that are increased in young mice which promote these same stem cells. Furthermore, the stem cells of old mice can be induced to act like those of young mice by administering the correct plasma substances. If it turns out that aging can be thus reversed by common pathways in all organs systems, the cure for aging may not be far away.

But even if we isolate all these products, the question will still arise as to what genetic pathway controls their production and the aging process. It is not enough to simply administer these products to aged individuals, for practical reasons if nothing else. It will be necessary to eventually change the genome of the human species to actually make it ageless, if that is our goal. It is not a coincidence that these products are produced to induce aging. It is clear that aging, and the pace of aging, is a genetic process, since each species ages at different rates and has its own unique lifespan. Each species is programmed to self destruct after a specific period, probably related to its unique requirement to mature and reproduce at a specific rate according to its evolutionary niche (the rate at which its own unique environment changes). If the environment changes quickly – the number of predators, food supply, weather, etc.—it has to reproduce quickly, and age quickly, for its offspring to produce the mutations to adapt. Since evolution always acts through mutations on the next generation, death is a necessary evolutionary trait. The survival of the new generation, and thus the species, is greatly enhanced if the parents no longer compete for natural resources, etc. after reaching sexual maturity. For those who object by saying that few animals in the wild die of old age but rather by predation or lack of food, I ask who does the predator most likely capture? The very young are normally protected by the herd while the old and slow are the stragglers who end up as prey. Furthermore, the very young are usually fed by the parents until they are able to find food while the grandparents are left to fend for themselves. The species is programmed for the new generation to mutate into a more adapted organism and for the old, which are no longer as suited to the new environment, to die off.

If we continue on this path to cure the disease of aging, we should consider the consequences of success. Some of the positive and negative effects of creating an ageless species are obvious, and some are not. In earlier postings, I have reviewed some of these considerations, but it might be time to revisit the topic since science is moving at such a rapid rate. It seems that few people are actually discussing the practical, societal, psychological and moral issues that will inevitably arise when the cure is found.

1.     Conboy I. M. et al. Nature (2005) 433, 760-764 doi:10.1038/nature03260
2.     Brack AS, et al. Science. (2007) 317 807-810.
3.     Villeda SA, et al. (2011) Nature 477: 90-94.
4.     Smith LK, et al. (2015) Nature Medicine 21, 932-937.
5.     Villeda SA. et al. (2014) Nature Medicine 20:659-663.
6.     Carlson ME, et al. (2009) Aging cell 8:676-689.
7.     Hanadie Y. et al. (2015) Oncotarget, Vol. 6, No. 14. pp. 11959-11978
8.     Sinha M. et al. Science 9 May 2014: Vol. 344 no. 6184 pp. 649-652 DOI: 10.1126/science.1251152
9.     Katsimpardi L. Science 9 May 2014: Vol. 344 no. 6184 pp. 630-634
DOI: 10.1126/science.1251141
10.  Egerman MA et al. Cell Metabolism, May 2015 22: pp 164-174.
11.  Hashizume O. et al. Scientific Reports, 2015; 5: 10434 DOI: 10.1038/srep10434

Monday, October 26, 2015

Your Thoughts?

Thank you for your input to date on THE DAEDALUS PROJECT.
Now I have included my latest mystery/thriller - THE CURE - to my manuscripts page.
All comments are very much appreciated.


Friday, January 30, 2015

Is Only 7% of the Human Genome Functionally Important?

ENCODE studies in 2012 (1) concluded that about 1% of the human genome codes for proteins and that about 80% of the genome is “biochemically active, and likely involved in regulating the expression of nearby genes.” These findings have produced a great deal of controversy and much hypothesizing among the scientific community. But a recent paper published in Nature Genetics (2,3) sheds doubt on those findings.

Researchers at Cold Springs Harbor created a computational method called fitCons which analyzes the changes in DNA letters that have occurred during long evolutionary periods across different species as well as during shorter periods between human individuals. In this way they hoped to identify which parts of the human genome were preserved and thus functionally important.

The present study showed that only about 7% of the letters in the human genome were preserved and are functionally important. Their conclusion is that “most of the sequences designated as ‘biochemically active’ by ENCODE are probably not evolutionarily important in humans,” and that “the much larger ENCODE-based estimates can’t be explained by gains of new functional sequences on the human lineage.”

Among the ENCODE papers, Kellis showed that 5% of the noncoding DNA is conserved across mammals and that an additional 4% is conserved among humans.

An obvious question that immediately arises if these findings are correct is what the activity shown by ENCODE in the other 73% of the genome that is not preserved by evolution is doing. Some of the critics of the ENCODE data have suggested that much of the ‘biochemical activity’ detected by their methodology is spurious and insignificant.

1.     Massachusetts Institute of Technology. "Biochemical functions for most of human genome identified: New map finds genetic regulatory elements account for 80 percent of our DNA." ScienceDaily. ScienceDaily, 5 September 2012. www.sciencedaily.com/releases/2012/09/120905154823.htm
2.     Cold Spring Harbor Laboratory. "Which 'letters' in the human genome are functionally important?." ScienceDaily. ScienceDaily, 20 January 2015. www.sciencedaily.com/releases/2015/01/150120160323.htm

3.     Brad Gulko, Melissa J Hubisz, Ilan Gronau, Adam Siepel. A method for calculating probabilities of fitness consequences for point mutations across the human genome. Nature Genetics, 2015; DOI: 10.1038/ng.3196

Saturday, December 6, 2014

Are You Religious or Spiritual?

The distinction between being spiritual and being religious has become more pronounced in the last hundred years. Whereas until the 20th century the two terms were used interchangeably, present day studies show a clear divergence of the terms and the characteristics of those who hold the two types of beliefs.

A three-year international study involving 57 researchers in 20 countries (1) found that humans are predisposed to believe in some sort of eternal being and an afterlife irrespective of their culture or teaching. Children below the age of three believe that their mothers and God can see inside a box, for example, but by the age of four they realize that their mothers are not all-seeing. Yet many continue to believe in an all-seeing God throughout adulthood. Adults across many different cultures believe in a duality of spirit and body, the former surviving beyond death.

In a study from Rice University (2,3), researchers found that more than 20 percent of scientists consider themselves to be spiritual but not religious. They used terms such as “individual, personal and personally constructed” to describe spirituality, whereas terms such as “organized, communal, unified and collective” were terms used to describe religious thought. They see both science and spirituality as “meaning-making without faith,” and spirituality as “seeking a core sense of truth…consistent with the work they do as scientists.”

Monday, July 21, 2014

Reversing Aging

In a study in 2013, a team at the Harvard Stem Cell Institute reported (1) that combining  the circulatory systems of an older mouse and a younger mouse in a surgical procedure called parabiosis improved the structure and function of the enlarged hearts of older mice, otherwise known as cardiac hypertrophy, which is a common cause of heart failure in humans. The hearts became smaller and there was molecular remodeling. They then found that the blood of older mice had less of a protein growth factor called GDF11 than blood of younger mice, and that administering GDF11 to older mice had similar effects as administering blood. GDF11 is also found in human blood.

In a separate paper (2) the same team showed that GDF11 reversed the structure and function of aged muscle to that of younger muscle and increased strength and exercise capacity. In a third paper (3) they showed that young blood, as well as GDF11 alone, improved the vascular structure of the brain and caused the creation of new nerve cells.

In yet another study at Stanford University (4) researchers found that administering young blood to aged mice can reverse pre-existing effects of brain aging at the “molecular, structural, functional and cognitive level.” Synaptic plasticity and dendritic spine density increased in the hippocampus of aged mice. Cognitive abilities improved in fear conditioning and spatial learning and memory. The study used the blood of young mice and did not try to identify any specific factors.

Friday, March 21, 2014

Scientific Evidence of a Pre-life?

There is an unshakable belief by most humans, irrespective of religion or cultural background, that they have a soul or some essence of themselves which is immortal. The question of spiritual immortality has usually been approached from the point of view of what happens to us after we die. But the same question can be asked in a different form: if there is a spirit and it is immortal, where were we before we were born? Though most of the lay literature has been focused on life after death, there is a small but growing popular literature (1,2,3), as well as websites (4), on pre -life memories, usually by small children. This literature is all based on anecdotal stories and thus disregarded by scientists.

A paper has recently appeared, however, in Child Development (5) by a Boston University team which tried to study a child’s conception of the pre-life from which he/she came. Their aim was to find out where beliefs of an immortal soul come from, whether it is hard-wired in our biological make-up or learned through religious teachings, cultural influences such as books and movies, or simply intuition. Their reasoning was that by asking very young children about their pre-life, there would be fewer cultural and religious forces which would have influenced them (especially since Catholicism, the religion of one group, teaches that life begins at conception).

They interviewed 283 children, ages 5-12, from two groups, one from an indigenous Shuar village in the Amazon Basin of Ecuador which has no concept of a pre-life, and the other from an urban area near Quito, Equador (Catholic). They showed the children drawings of a baby, a young woman, and the same woman pregnant. They then asked the children a series of questions about their concepts of the baby’s abilities, thoughts and emotions during three periods: as a live baby, as a baby in the womb, and before conception.

Monday, February 10, 2014

Origin of Species - An Example

How new species arise has been a question at the core of evolutionary theory and a point of challenge for those forces which adhere to an intelligent designer as the source. The idea of a new species arising from a pre-existing one seems to require many simultaneous changes, many of which could prove lethal. Yet in a paper recently published in Cell Reports (1), it appears that the process isn’t all that difficult or rare. Only relatively few genetic changes are needed for the evolution of a new species, even when two divergent populations remain in contact and continue to mate.

The researchers at the University of Chicago analyzed the genomes of two closely related butterfly species, Heliconius cydno and H. pachinus. They found that the initial divergence occurs in a small fraction of the genome, usually related to wing color pattern, which is important in mating and predator avoidance. Once started, however, added changes in other genes rapidly occurred in escalating divergence, usually in neutral regions of the genome.

The divergent regions were shown to be the result of both natural selection and adaptive introgression (the movement of genes through backcrossing of hybrids with parental species, since the hybrid species were still able to mate with parental species). The process of new species creation was shown to be a gradual one, rather than the result of a sudden split between two divergent populations. According to the authors, the mechanism of selection and adaptive introgression in the creation of a new species demonstrates “the link between mircroevolutionary processes acting within species and the origin of species across macroevolutionary timescales,” thus addressing the objection put forth by proponents of intelligent design that evolution explains changes on a micro level but not on a macro level.

How important this type of speciation is to other organisms remains to be seen, but the fact that it can occur in butterflies should send some deniers of evolution back to the drawing board.

1.     Marcus R. Kronforst, Matthew E.B. Hansen, Nicholas G. Crawford, Jason R. Gallant, Wei Zhang, Rob J. Kulathinal, Durrell D. Kapan, Sean P. Mullen. Hybridization reveals the evolving genomic architecture of speciation. Cell Reports, 2013 DOI: 10.1016/j.celrep.2013.09.042

Sunday, December 15, 2013

Some New Aspects Of Cellular Aging

The more theories there are to explain a set of facts, the less we understand it. There is no better example of this than the theories of cellular aging. A short list of the theories of the cause of the aging process include: the telomere length theory, the reproductive cell cycle theory, the DNA damage theory, the autoimmune theory, the free-radical theory, the cross-linkage theory, the error accumulation theory, the somatic mutation theory, the reliability theory, the wear and tear theory and so on. It resembles more the story of the blind men who feel a different part of the elephant. Researchers are describing some genetic and biochemical findings associated with aging, not the cause.

A recent study in Nature (1) makes the task even more difficult. Until now, most researches thought that aging is inevitable in most if not all species and starts occurring after the peak reproductive age. Researchers at the Max Planck Institute, however, found an extraordinary diversity in the processes of aging among the 46 species they studied, ranging from the lifespan of the fruit fly (a few days) to humans (roughly 100 years) to hydra (centuries, practically immortal). They studied 11 mammal species, 12 other vertebrates, 10 invertebrates, 12 plants and one algae. What they found was that most of our ideas on aging are false since they are based mostly on mammals and birds, which are not representative of all species on the planet. Some species become weaker with age (e.g. humans, other mammals and birds) others become stronger with age (e.g. tortoises and some trees) while other remain the same (e.g. Hydra and the hermit crab).

Wednesday, October 23, 2013

The Cambrian Explosion: Could Such Rapid Evolution Happen Naturally?

The Cambrian Explosion refers to a period around 540 to 520 million years ago during which arose an abrupt increase in the number and types of animal groups as evidenced by the fossil record. This sudden increase in the rate of evolution has caused some to argue that it could not have happened naturally. But there has never been an accurate measurement of the actual rate of evolution during this period, until now.

A new study in Current Biology (1,2) has found the rates of “morphological and genetic evolution during the Cambrian explosion were five times faster than today—quite rapid, but perfectly consistent with Darwin’s theory of evolution.” The study focused on arthropods, the most diverse animal group in the Cambrian period and today, but the results are considered to be generally applicable to the other animal groups. 

Theories of how the Cambrian Explosion happened generally fall into three main categories: genetic, ecological and environmental/geochemical. In the latest edition of Science (3,4) Professor Paul Smith of Oxford and Professor David Harper of Durham University propose that no one theory explains it all, but that a ‘cascade of events’ led to the sudden explosion in the number and diversity of species. It is becoming clear, however, that the oxygenation of the earth’s atmosphere played a major role. Large organisms cannot exist without a minimum amount of available oxygen (5). Large amount of evidence has shown that two geological periods of oxygenation occurred, one in the Precambrian period and another two billion years earlier (6,7). During the Neoproterozoic era that preceded the Cambrian Explosion, the geological conditions were chaotic, with the breakup of the supercontinent Rodinia and a period of prolonged global cold during which oceans were covered with ice from pole to pole and were low in oxygen content. During this time oxygenation occurred non-linearly and organisms evolved that were able to survive both aerobically and anaerobically, perhaps leading to even greater diversity.

Monday, September 30, 2013

The Light Saber: Solid Photons, Fact or Fiction?

The light saber. It looked magical when Obi-One Kenobi first whipped it out in the bar in the spaceport town of Mos Eisley on the planet Tatooine; light energy that has the solidity of matter and which can cut through anything. I never quite understood its usefulness in an advanced world with laser guns and intergalactic travel, but never mind. It was graceful, beautiful, a wonderful combination of old world elegance and new world technology. But it is a work of fiction that isn’t real, right? Right. Until now.

In a September 25 paper in Nature (1), a team of Harvard and MIT scientists have created a new state of light that has properties of matter, much like the light saber. Photons are normally without mass and they do not interact with other photons. In this study, though, two photons were fired through a cloud of cold rubidium atoms just a few degrees above absolute zero. As the photons passed through the cloud, they started interacting with the rubidium atoms in a series of exchanges of energy (an effect called the Rydberg blockade) resulting in the two photons exiting together as a single molecule, bound together into “polarization-entangled photon pairs” which acted as though they had mass.

Are there any practical applications? Yes, in quantum computers. But I am still holding out for my light saber.

1.     Ofer Firstenberg, Thibault Peyronel, Qi-Yu Liang, Alexey V. Gorshkov, Mikhail D. Lukin, Vladan Vuletić. Attractive photons in a quantum nonlinear medium. Nature, 2013; DOI: 10.1038/nature12512

Monday, August 26, 2013

God, Myths, and Our Tired Concepts

The faithful referred to him as “The Light of the World.” He was born of a virgin who was referred to as “Mother of God,” he was part of a Holy Trinity, celibate throughout his life, extolled justice, renounced riches and sensual things, had twelve apostles and viewed life as a struggle between the forces of Good and Evil. He preached that there will be a Judgment Day at which time the dead will be resurrected, the earth will experience a final conflict between the forces of light and darkness and the present order will be destroyed. Thereafter, light will forever reign on earth. He preached that this duality continues in the afterlife in the form of Heaven and Hell. After he completed his earthly mission, he had a Last Supper with his twelve apostles and ascended to Heaven, after which his followers conducted ceremonies that included the drinking of wine and the eating of bread to symbolize his blood and flesh. Baptism was practiced as a ritual of purification. December 25th was celebrated annually as his birth and Sunday was the holy day of the week.

No, it isn’t Christianity, but Mithraism, the last pagan religion of the Roman Empire. It began in Persia in the 6th or 7th century BCE and eventually spread through India to China and throughout the Roman Empire. Relics of the Mithraic religion have been found in Britain, Italy, Germany, Hungary, Turkey, Romania, Bulgaria, Armenia and throughout North Africa. It was the favorite religion of the Roman soldiers because it celebrated brotherly love and physical action in the name of justice and truth. It lasted a little over three hundred years and was then overtaken by Christianity, which didn’t hesitate in borrowing a few items along the way.

Saturday, August 17, 2013

Consciousness, Near Death Experiences, and Quantum Mechanics

Near Death Experiences

Near death experiences (NDEs) have been extensively documented, both in popular literature and in scientific studies. Though most older studies were retrospective, sometimes interviewing patients years after their experience, several new studies have been conducted prospectively. As reviewed by van Lommel (1), in prospective studies in Holland (2), the US (3), and Britain (4), cardiac arrest patients were interviewed as soon as possible after their resuscitation. Of these, 6-12% (depending on the study) reported an NDE with high enough clarity to be able to describe what they saw. In the Dutch study, for example, 50% of patients with an NDE reported awareness of being dead, 25% had an out-of-body experience, 30% reported moving through a tunnel, 13% had a life review, and 8% experienced a border. Neither the duration of the cardiac arrest, nor the need for intubation, nor induced cardiac arrest in electrophysiological stimulation had any influence on the frequency of NDE. Nor was the frequency of NDE related to the administration of drugs, fear of death before arrest, foreknowledge of NDE, religion or education. The frequency of NDE was higher in patients who were less than 60 years old, who had more than one CPR during their hospital stay, and who had experienced an NDE previously.

All of these patients had electrophysiological evidence of no brain function during the CPR. Many studies in both human and animal models have shown that electrical activity in both the cerebral cortex and the deeper structures of the brain are absent after a very short period of time. The first ischemic changes in the EEG are detected an average of 6.5 seconds, with progression to a flat EEG pattern occurring within 10-20 seconds, after the cardiac arrest (5-8). In all three studies it was concluded that all patients who experienced NDEs had a transient loss of all functions of the cortex and brain stem. Even though these patients were all unconscious with no EEG pattern they experienced clear, logical consciousness (in describing what went on in the room while being resuscitated during their out-of-body experience, the description of the tunnel, light, review of their lives and meeting with dead relatives, even those that some did not know were dead or even that it was their relative - in one case a patient met a man while in another dimension whom he did not know, yet who he found out years later was his dead father).