Saturday, November 28, 2015

Ageing-Disease Conundrum

In line of recent blog post of whether ageing is a disease or not? A news report published in "New Scientist" brings out an important angle or reason is to why there is a need of including ageing as disease in upcoming International List of Causes of Death  (ICD)-11 classification. Homeostasis is one of the most favourite phenomena of nature.  Hence, every idea has its own merits and demerits. 

Upon asking an important question on a scientific forum wether ageing is a disease or not. I was given following reply by a distinguished Professor:

  1. yes ("disorder of structure or function in an animal or plant of such a degree as to produce or threaten to produce detectable illness or disorder").
  2. no ("the quality which identifies disease is some deviation from a biological norm").

Is ageing a disease? - ResearchGate. Available from: https://www.researchgate.net/post/Is_ageing_a_disease [accessed Nov 28, 2015].

I can see some clear confusion here. When we see definition "2" as mentioned above; ageing leads to Cardio vascular abnormalities, Central Nervous System (CNS) abnormalities, anatomical abnormalities, fatigue, prostate problems in males and many other problems. Hence, the question Is it not deviation from biological norm?

Moreover, one of the most important question "How much can human life span be extended"? is one of the top 25 questions to be answered, published by Science magazine.

Not including ageing as a disease has created many restriction towards availability of collaborative efforts, funding and other resources for carrying out cutting edge research to solve the problems pertaining to ageing. The question of including ageing as disease has been more of an ethical instead of scientific conundrums as pointed by Dr. Alex Zhavoronkov in his recent press release here.  

Friday, November 20, 2015

Beauty Contest Judged By Artificial Intelligence....

After looking at the various facets of ageing and its implications on human life. Here, I bring to you an incredible announcement made by leaders in the field finding newer ways of diagnosis and fighting ageing.


"First International Beauty Context Judged by Artificial Intelligence Jury"


This contest is partnered by big names like Nvidia and Microsoft. You can get more details about rules and regulations on the following site.

So go and upload your photo and get the newly developed AI decide if you are beauty queen or king. You can register online and be a part of this unique contest here.

Thursday, November 12, 2015

Is ageing really a disease?

From my previous discussions on

A) Personalised cancer therapy

B) Cancer and ageing relation

C) Important breakthroughs in cancer and ageing

D) Long living rats

E) Scientific perception of Indian scripture for longevity: Dr. Sinclair and Dr. Zhavoronkov's idea.

It is surprising that ageing is not been classified as a disease.

It is indeed debatable that whether ageing is a disease or a generalised and universally accepted phenomenon? Being a pharmacist or medical practitioners we normally follow guidelines of standards set by World health organisation (WHO), Centre for disease control (CDC), United states pharmacopeia (USP), British pharmacopeia (BP), Indian pharmacopeia (IP) and others.  

Recently, a paper published by Dr. Alex Zhavoronkov raises a cascade of questions as discussed below.

If "Ageing" is never been considered as a disease up till now then why are we trying to cure it? or slowing down the process? or trying to find out a molecule which can provide longevity? Why the health supplement industry is growing enormously compared to any other pharmaceutical industry?

It is evident that cross over from ageing to pathological conditions like age related diseases often takes place as shown in figure. As a result we have deadly diseases like cancer, cardiovascular diseases, central nervous system diseases and others. The paper clearly explains how the united efforts to fight against ageing is most important from both scientific and economic perspective. Importantly, the paper discusses about the reasons why it is essential to classify ageing as disease in up coming 11th international statistical classification of diseases and related health problems (ICD-11), expected to be finalised in 2018.

Significance of this paper and insight of Dr. Zhavoronkov, CEO Insilco Inc. is discussed by www.eurekaalert.org. Please click here for more details.

-Paper can be downloaded from here.

Friday, November 6, 2015

Anti-ageing: A reality or myth?

From Mahabharata to Science

The idea of Not Ageing is indeed like looking into an indian mythology of Mahabharata. 
Where people are mentioned to have unusually long lives. It is one of the oldest known Indian scripture researched by many archeologists, medicine experts and physicist. Many known scientists have known to acknowledge this intriguing scripture for their well known scientific works that includes Albert Einstein or J. Robert Oppenheimer. 
Depicted Image of Sage Vyasa

It is said that people had long lives in ancient era of Mahabharata that is around 1000 years. May be this is a truth or myth. Sage Vyasa who is known to have written this ancient scripture lived across approximately 6 generation of kings and have narrated their stories in Mahabharata. Some people with their logical reasoning think that he may have lived around 130 years without any health issues. Whereas, some assume that he may have lived way longer than that.
             
 Lord Krishna and Bhisma (symbol of longevity)




Important point is that we have reference of longevity in ancient literature, question is do we believe in having scientific basis for long and healthy life?

Voice of Insilco Inc, CEO: Dr. Alex Zhavoronkov

It shows a far fetched vision of company which truly believes that longevity is possible. But is it a dream/ struggle or some kind of myth? Evidence of naked mole rat discussed previously in our blogs suggests that this may be possible. As it is the only rodent, which points in the direction of not only having resistance towards cancer but also towards other age related diseases. 

A group of scientists believe that at cellular levels,  mTOR and Telomerase may play a crucial role in cancer therapy and attaining longevity as discussed previously. On the other hand Prof. David Sinclair in his video published in TEDx series explains his life's journey to find reason behind ageing.



He talks about one more miraculous protein which may be involved in ageing process called as  Sirtuin.                                        .............................................. yeast ageing mechanism click here.
                                    ............................................... role of sirtuin in age related diseases click here.

Perhaps, this insight may help in unrevealing deeper mysteries of long life and a way to treat cancer by using Personalised medicine method.

Tuesday, November 3, 2015

Cancer Resistant And long Living Rodent

In our previous blogs we discussed about Peto's paradox. We also discussed about personalised medicine for cancer therapy and funding possibilities for fighting against cancer.

In most published literature mice  are often used as model to extrapolate molecular research for cancer and ageing to human conditions. This extrapolation often fails due to variation in molecular and metabolic levels.  For more details please check here.

Further, we also discussed recent strategies of using targets like mTOR and Telomerase for treating cancer and age related diseases.

Important question is mice (a rodent species) be used for getting useful information about problems of fighting cancer or longevity?

video of showing of naked mole rats can help preventing cancer

It is said that "Answer to major natural  problems will come nature". Somewhere in 2013 it was discovered that a species of mice, which shows resistance to cancer it is called as "Mole Rats"

Although, it is a ugly looking nude mice but it is an interesting animal showing resistance to cancer. 

For more details about the animal please read here.

A simple molecule called hyaluronic acid (HA) produced by this animal is responsible for preventing development of cancer. However, scientists believed that there may be more to this idea. They think that other mechanisms along HA induced effects may play role in preventing developing cancer in mole rats. 

Unusually, molecular weight of HA from mole rat is five times higher than humans which provides protection to mole rats against cancer.   Scientific paper can be accessed here.

Please click here to check genome sequence web-portal for more in-depth research.

This rat seems to be resistant to age related diseases including cancer. Further, it has striking life of 30 years, that is longer than the normal mouse with life span of maximum 4 years. This makes mole rats an unusually long living rodents. More details can be seen here.

Hence, unfolding of the biomechanics of this organism may help us to find newer ways of cancer therapy and attaining longer life.

Some sources says  "If a human was to have same lifespan as a naked mole rat, relative to its size, they would live for up to 600 years"............................click here.


Recently, in 2015 identified new protein product pALTINK4a/b  which may be responsible for inducing longevity in these rats. They were able to correlate dependency of expression of pALTINK4a/b  in presence of high molecular weight HA in mole rat............................................ This may finding can be accessed here.

May be his new finding may help to find newer ways of longer life.



Thursday, October 29, 2015

Important Breakthroughs In Cancer and Ageing

Personalised medicine with mTOR inhibitors and Telomerase modulators may serve as important breakthroughs in medicine. May be it can fetch more attention of organisations like Cancer Research UK, NCI and other funding agencies help in fighting Cancer and Ageing related problems.

mTOR is nutrition driven pathway. Dietary restrictions causes down regulation of mTORC1 activity.  Hence, targeting it with its inhibitor may help in providing anti-ageing and anti-cancer effect as shown in figure below.


It shows effect mTORC1 effect on longevity.  A cancer cell needs lot of energy because of its increase growing rate. Inhibiting mTORC1 with specific inhibitor helps in providing longevity.

Scientific paper mTOR and longevity can be accessed from here

According to Peto's paradox, chances of acquiring cancer is more in humans compared to large animals like elephants or whale even though these big sized animals have large number of big sized cells compared to humans.

Metabolic perspective of Peto's paradox and cancer  can be accessed from here

It's observed that small number of cells divide faster than big sized cells. As a result there are chances to acquire large number of genetic errors in rapidly dividing small cells. And these errors simply keeps on accumulating due to cell division. These accumulation of errors leads development of cancer. Moreover, with every cell division Telomere located at the end of DNA also keeps shortening. So basically with every cell division a piece of information is lost due to DNA damage. Telomerase enzyme helps in prevention of this loss and maintains the Telomere length. This in turn helps in maintaining the original length of DNA and prevents chromosomal shortening.

Details of this basic biology can be visualised in following Youtube video.
Basic function of telomerase.

Identification molecules which can increase synthesis of telomerase has been of prime importance.  These agents can also help in reversing ageing or may be useful for cancer prevention. Understanding of how telomerase works can be seen from a video of famous scientist Prof. Michio Kaku.




Friday, October 23, 2015

Ageing-Cancer dependency

Cancer is basically defined as uncontrolled multiplication of cells.  On the other hand, ageing is characterised by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death.

Cancer is one of the age related disease. The chances of occurrence increases with age as reported by Cancer Research UK, Centre for Disease Control (CDC) given graphs below

For more info click here

For more info click here

These tables clearly shows relation of ageing and cancer in clinical scenario. 

At cellular level relation of cancer and ageing can be visualised from the following image. As we know that cells in cancer condition grows faster hence they also catch up to the ultimate fate of death faster as compared to normal tissue. 


During normal ageing, stem cells accumulate damage and subsequent stress-dependent changes (for example, de-repression of the CDKN2a(INK4a/ARF) locus or telomere shortening). This leads to the increasing abundance of senescent cells (large blue cells) within differentiated tissues. Incipient tumours, arising directly from stem cells or from more committed cells, undergo rapid proliferation (small red cells). These pre-malignant tumour cells rapidly accumulate damage, in part owing to the presence of oncogenes, leading to a higher proportion of tumour cells becoming senescent (small blue cells). Tumour progression to full malignancy is favoured when tumour cells acquire mutations that impair the senescence program (for example, mutations in Trp53 or CDKN2a).

Biology of ageing-cancer relation is accessible here

Most commonly explored pathway for the treatment of ageing and at the same time cancer is m-TOR. I believe it is a wonder pathway for treatment of variety of other age related diseases. 

Moreover, this pathway serve as link between cancer and ageing. So inhibiting m-TOR not only stops cancer multiplication but also helps in increasing life expectancy of cells. It is ironical to say that inhibition of m-TOR helps in inhibiting two different ends of life viz. cancer (symbolises uncontrolled cell division) and ageing (symbolises death). 

Scientific paper for correlation of mTOR with age related disease can be downloaded from here

Hence, personalised cancer medicine by Pathway Pharmaceuticals and Insilco Inc. will help in developing newer strategies of increasing the life expectancy of not only cancer patients but also other individuals suffering from age related diseases.

Monday, May 4, 2015

Insilico Medicine SuperPharman Challenge: Looking for Superheroes to Transform Big Pharma

New Super Jobs @ Insilico Medicine Announced



Aging fighters at Insilico Medicine are looking for relentless doers who dream big, but are not afraid to get their hands dirty with basic tasks. Doers, who have trouble sleeping at night, because they know that millions of people are suffering and dying of cancer and age-related diseases and their own clock is ticking as well. Doers with both programming and database management skills and knowledge of biology. You will need to know or quickly learn how to use huge multi-omics data to find alternative uses of currently available drugs and distribute many micro tasks to the crowd, freelancers or colleagues, while keeping the big picture in mind. 

We know that we are looking for a needle in the haystack, but this is how our team has come to be and you will be in great company. We have relentless super heroes in the US, UK, Switzerland, Poland, Israel, Russia and China. If you know someone amazing, who fits that profile amazing, ask him. Maybe he or she is already working for us. He goes through the day doing a boring academic job, but at night he is hacking away.

Our first frontier is transforming the pharmaceutical industry, repurposing known drugs and finding the new ones. When we launch, the world will become a better place. And if you are that super hero with bold ideas and hands on experience, ready to unleash maniacal energy to hack aging, send us a signal and we will respond right away or start watching you to see if you fit.

Here is a link to what Insilico Medicine is doing: 


In partnerships they can also do in vitro and in vivo validation, humouse clinical trials and even organ-on-a-chip and body-on-a-chip validation. 
They are looking for someone with similar skill set and energy as Alex Zhavoronkov (www.linkedin.com/in/zhavoronkov) to work together with him, gradually replace him and then find someone to replace yourself as the company grows or you decide to start a subsidiary. 

Minimum requirements:
  • Python, MySQL, Hadoop, AWS Services, IBM Watson
  • Experience working with multi-omics data and/or clinical trials/biomedical text data
  • SVM and deep learning algorithms
  • Basic knowledge of signaling and metabolic pathways
  • Experience working with GEO, ArrayExpress, KEGG, TCGA, LINCS, Connectivity Map, Drugbank, Clinical Trials, WHO databases, etc.
  • Personal network of contacts in academia and large pharmaceutical companies
  • Excellent writing skills
  • Ability to give public talks and generate publicity is a plus
  • Knowledge of Russian, Chinese or Hebrew is a plus





Sunday, January 4, 2015