As we shift our view of aging from a natural part of life, to something modern medicine can possibly prevent, the next step will be finding ways to indefinitely keep ourselves healthy and stall death for as long as possible.
The human transcript tome is the sum of all R N A transcripts in our cells.
It is different from the genome because each gene can code for multiple proteins, while each transcript only codes for one protein.
Transcript O mics and epigenetics study how genes are expressed so we can gain closer insights into how proteins are made.
Gen O mics and D N A editing technology have made many bioethicists nervous, because the technology isn’t accurate, and changing a gene can get rid of good proteins just as easily as it can get rid of bad ones without us even knowing.
There is also the ethical debate about making permanent genetic changes and passing them onto our children.
But there is a less controversial way to make temporary changes, through transcript O mics and R N A eye.
While genomics deals with the genes in our bodies, Transcript O mics and Epigenetics deal with the varying amounts that these genes are expressed, looking for ways to turn on or turn off the molecular switches that transcribe them.
A new study detailed in the journal Nature, “Splicing factor 1 modulates dietary restriction and TORC1 pathway longevity in C.
elegans”, has uncovered a relationship between aging and R.N.A transcript splicing, which is what allows a single gene to produce multiple proteins.
A team of re searchers, led by the Harvard T H Chan School of Public health, wanted to find out if the act of R N A transcript splicing had an impact on the length of our lifespans.
To find out, they designed experimental setups, using a roundworm called C.
elegans, which only lives for 3 weeks so they are a great test subject for aging research.
Using fluorescent genetic tools, the team was able to observe the R N A transcript splicing of individual genes in the roundworms’ transparent cells and identified certain patterns of splicing that indicated youthfulness.
Other splicing patterns lead to premature aging, meaning transcript O mics has now begun uncovering previously unknown aging biomarkers, outside of the genome.
This research could lead to new breakthroughs in anti-aging treatments that would allow humans to indefinitely keep ourselves healthy, stalling death for as long as possible.
Many technologies have been proposed.
The most popular ones being, number one, R N A I, an interference technique for gene expression, number 2, C2C2, a gene editing technique for R N A, and number 3, epigenetics and sirtuin drugs.
The first method is called R N A eye.
M R N A transcripts are the messengers that carry information from your genome to the ribosome, the cell’s molecular factory, where your genes are translated into amino acid chains to become your proteins.
But R N A molecules can work the other way too.
It can turn that information back into D N A, the same way retro viruses do when they try to add their genes into your cells, using a protein called reverse transcriptase, which I’ve already covered previously.
Instead of M R N A, regular R N A transcripts can also become T R N A, which carries amino acid building blocks to the ribosome.
But they can also interfere with other R N A molecules through something called R N A eye, where it chops up the R N A transcripts so that they are never turned into protein.
Thereby silencing a gene without even touching the genome.
R N A eye can be seen as a more ack Urit alternative to genome editing, because it attacks unwanted byproducts of a gene, rather than the gene itself.
Since some genes code for multiple proteins, destroying a gene to get rid of one bad protein can get rid of many other good proteins as well, so genome editing can do more harm than good.
R N A eye gets around this problem by only attacking specific R N A messengers of the gene, destroying transcripts for the one undesirable protein but letting other transcripts continue to the ribosome.
This method gets rid of the one protein you hate, while keeping all the other good proteins around, even though they are all made by the same gene.
R N A eye works by finding double-stranded R N A molecules with a protein complex called Risk.
The Risk complex targets strips of M R N A that fit together with its base pair code, then destroys whatever pieces of R N A happen to match.
Chopping them up with a protein called Dicer, then disintegrating the fragments with a protein called Slicer, which shreds them for good.
This system can be programmed to hunt down and destroy specific pieces of R N A and prevent a bad protein from being constructed.
We’ve known about R N A eye for a long time, ever since scientists first engineered white flowers from purple flowers, chopping up the transcripts for the pigment proteins, and turning the flowers white.
The problem is that we’ve still had trouble getting it to work efficiently as a therapeutic treatment.
Although it is still very useful for research, like for example, when we want to see what happens if specific transcripts of a gene are suppressed.
Many scientists entertain the idea of a human Transcript tome project, similar to the human genome project, but with cutting-edge R N A sequencing technology.
We are not only hoping to understand all of our genes, but every possible protein made by each of those genes as well.
But it’s a very tedious process, because it involves targeting transcripts one by one, and knocking them out to see what happens to the organism.
In aging re search, R N A interference is used on C Elleganz worms to try and identify the transcripts for aging, so that we could develop therapeutic treatments to block bad proteins.
DAF-2 in C elegans is one such aging gene, well known for insulin signaling, but also for regulating lots of other genes, like DAF-16.
When the transcripts of the gene are blocked, it dramatically influences the worm’s lifespan by up to almost 150 percent.
The next stage is finding and testing the analog in humans.
Molecular biologists like Doctor Cynthia Kenyon, have already made it their life’s work, publishing several papers.
However, while R N A interference is great at blocking bad transcripts, it can’t really change them.
Which brings us to C2C2, a gene-editing system for R N A that does exactly that.
Many are already familiar with Crisper, a molecule that “snips” sections of genetic sequences and inserts newer strands of D N A for a customized genetic code.
It has even been shown to remove the genome of the H I V retrovirus from infected cells.
I’ve already talked about Crisper previously as a gen O mics tool for editing D N A, but we are also developing a transcript O mics tool for R N A.
A new study published in the journal science, “C2c2 is a single-component programmable RNA-guided RNA-targeting Crisper effector”, revealed that a new crisper system called C2C2, can manipulate and edit our R N A sequence.
Editing our transcript tome rather than our genome will allow us to make temporary changes to our genetics, rather than permanent ones.
While we already have R N A interference technology, C2C2 might have even more potential as a groundbreaking platform for medicine and life science research.
C2C2 was discovered in a bacterium called Lepto trick eye shahii, which used it to protect itself from R N A viruses for millions of years.
C2C2 works by cleaving incoming R N A strands, and destroying the virus genes before they can do any damage to the bacteria.
While R N A eye can already block messages from being transcribed, C2C2 has the potential to change these messages altogether and create your own customizable transcript tome.
This method bypasses the controversial issue of designer babies and genetic inheritance, opting for a more regulated and controllable form of genetic engineering instead.
The Third method is Epigenetics.
Epigenetics is the study of gene expression and it focuses on the molecular factors, that can either help or prevent genes from being transcribed more often.
Epigenetics involves molecular modifications that can switch certain genes on or off, but don’t change the D N A sequence itself.
Imagine 2 twins separated at birth, one is raised with junk food, alcohol, abusive parents, and given a stressful job.
Meanwhile, the other twin is given a proper diet, regular exercise, great parents, and strong loving relationships.
When the twins meet up in 50 years, you can expect to see a lot of biological differences between them even though their genetic codes are exactly identical.
Many re search projects, like the Danish twin study, have shown that the genome isn’t everything and that lifestyle factors affect how your genes will be expressed.
Everything you do over the course of your life will impact your epigenetics and many of those changes can be passed on to your children or grandchildren.
In fact, the lifestyle decisions your grandparents made might still affect you to this day.
The D N A molecule carries a negative charge and is wrapped around positively charged proteins called Histones, forming what looks like little beads on a string.
Histones can wined your D N A either tightly or loosely, to influence their expression.
Your genes also receive outside instructions from chemical compounds called methyl groups, molecular switches that bind to your genes and block their transcription.
Other factors, called Acetyl groups, do the opposite, binding to the histone proteins to unravel your D N A, and increase expression of a nearby gene.
These factors are different in every type of cell in the body, since each one has a specific methylation and acetylation pattern.
Methyl groups and Acetyl groups rearrange based on your environment, diet, lifestyle, stress, and amount of sleep.
With that said, it can change throughout your life, especially during periods of rapid aging or puberty.
If Genetics are your cellular hardware, then Epigenetics is the software telling the hardware what to do.
The systems biology lab at U C Merced recently published discoveries, about an epigenetic factor called Jumonji. A study called, “A histone de methylase, called K.D.M 3 Eh, regulates the transcriptional program, of the androgen receptor in prostate cancer cells”.
This factor not only affects how an entire network of cancer genes works, but is often miss tuned, causing it to affect the rate that the genes are transcribed into M R N A.
Epigenetic factors put certain chemical modifications on their target genes to switch their activity on or off, which can lead to altered metabolism, cancer, or even slower aging.
The free radical theory of aging, affecting D N A in the mitochondria, has long been the dominant theory of aging, but re searchers from the University of Sue Coo Ba in Japan have demonstrated an Epigenetic theory of aging.
In a study called “Epigenetic regulation of the nuclear-coded GCAT and SHMT2 genes confers human age-associated mitochondrial respiration defects”, published in the journal Nature, researchers found no observable differences in the number of mitochondrial D N A mutations between the older and younger cells but did find certain epigenetic factors, such as the addition of certain proteins to the mitochondrial D N A, creating defects associated with old age.
The researchers then removed these epigenetic factors, which seemed to turn the “old” cells back into “young” ones.
The epigenetic factors seemed to be blocking transcription of a gene that helps make the amino acid called glycine and affected the cell’s ability to produce energy.
To make sure it was actually the lack of glycine causing the problem, the researchers bathed the 97 year old cells in glycine, which also seemed to correct the issue.
So epigenetics definitely does contribute to the rate we age, which brings us to the big question.
Can we develop drugs to manipulate the rate, that our aging genes are transcribed?
Aging Biologists, like David Sinclair from Harvard University, seem to think so.
Doctor Sinclair’s lifes work was on the epigenetics of 7 aging genes, called “the Sirtuin Genes”.
The proteins produced by the Sir Too Inns clip off chemicals that bind to our genes, and restore their transcription, which prevents aging and disease.
Sirtuin proteins also influence the methyl groups and acetyl groups, that dictate the frequency of gene expression.
The sirtuin genes are stimulated naturally when we exercise or don’t eat, but are shut down when we do unhealthy things, like eat junk food.
All mammals have 7 genes, from SIRT-1 to SIRT-7, that seem to have a role in preventing age-related conditions like heart disease.
In 2012, re searchers at Barra Lan university published a study, where the expression of SIRT-6 in mice, helped them live 16 percent longer than untreated male mice.
Probably because Sirt-6 is believed to be a tumor-suppressing gene that helps resist cancer.
An anti-aging gene called SIRT-2, has a similar sequence to a gene on C.Elegans called DAF-16, which raises the question, of whether there are universal anti aging genes, common to all organisms.
Sirt 2 is often called the quote-unquote “longevity gene” because adding just one extra copy of it, can extend the lifespan of yeast by 30 percent, with varying effects in rodents as well.
“Rez verra troll”, a nutrient found in grape skins and red wine, has been known to help with Heart health, as well as the expression of the Sirt-1 gene.
Sinclair’s team found that when you feed this molecule to obese mice, they still live much longer and much healthier than regular mice.
But still, don’t go drinking yourself into a frenzy, because the mechanism of rez verra troll is still controversial.
As a result, Doctor Sinclair started a company called Sirtress, to try and look for new kinds of synthetic molecules that can better activate the sirtuin genes.
He successfully sold his company to Glacksow Smith Klein for 720 million dollars, and sparked a revolution in Sirtuins research.
Hopefully it will lead to less controversial drugs that can also activate the sirtuins more potently than rez verra troll can.
Other lifestyle factors, like a Calorie restriction diet, which I’ve covered earlier, have also been shown to activate transcription of the sirtuin genes.
This low calorie diet promotes the Sirtuin genes, by a molecule called N A Dee, which is commonly found in the Krebs cycle.
Sinclair’s team discovered all this when they removed the SIRT-2 gene, from organisms like yeast. They found that the removal of the gene always removed the positive effects of the caloric restriction, so there is clearly a molecular link.
When you take away the sirtuins, the diet doesn’t work.
To this day, a calorie-restricted diet, where you cut your daily caloric intake by 30 percent, has proven to be the only scientifically confirmed method of slowing aging in rhesus monkeys.
There’s no data on what the diet does to humans, because test subjects doing the diet tend to cheat too often, Probably a good indicator of why nobody wants to do it.
It would be better to have a drug that would elicit some benefits of a caloric restriction diet, without us actually having to do it.
Luckily, it is theoretically possible to reap the benefits of calorie restriction without the adverse effects of not being able to enjoy food, but it will require a better understanding of epigenetics.
Overall, there are many ways we can influence our genetics without changing our D N A, and many of these factors can directly influence our lifespan.
Many R N A and transcript O mics technologies are on the horizon, but until then the only way to influence your aging genes is your lifestyle.
Everything you do changes your genetics, and in turn, the genetics of your children and grandchildren.
It’s a whole new kind of existential responsibility.
With that said, try to create a healthy life for yourself, so that your children can live one too