Animals who defeated ageing.

Cellinsight Everything about human ageing and related diseases

Immortal animals

Nothing is forever in this world, death is certain, one day it will visit us. But there are some creatures that never die by natural aging process. Human cells are capable of dividing only 50 times, later the cells entered the senescence stage, and this is the exact reason for aging. Any animal which is not experiencing senescence can defeat ageing, today I am going to tell about such types of animals and how they live without the fear of ageing

1. Jelly fish (Turritopsis dohrnii) 

Immortal jellyfish
(Image credit goes to Wikimedia) 

Jelly fishes are sea animals, included in the phylum coelenterata (cnideria). Turritopsis dohrnii is a species of jellyfish which is known as immortal jellyfish. Jellyfish reproduce both sexually and asexually.The life cycle consisted of three main stages, planulae,polyps and medusae. fertilized egg give birth to planula. The Planula is the larval stage, after few days it attached to any solid substrate under water and later transformed to polyp. Polyps later start to bud off another larva known as Ephira. These larvae

grown in to mature form of jellyfish, the medusae. When medusae injured or sick they revert back to polyp stage again within three days.

2. Lobsters

Lobster

Lobster is a member of phylum Arthropoda
and sub phylum  crustacea. Lobsters not experiencing senescence, they produced adequate amounts of telomerase enzyme. The length of telomere is constantly maintaining by this enzyme, so it's length not reduced after each cell division. Lobsters grow too big size for their shell. Unfortunately shell shedding and grow another exoskeleton cost very high amount of energy. Larger the lobster more energy required for moulting and rebuilding of shell. Shell collapse is one of the reason for their death. It also die because of diseases, predation etc.   

 3. Hydra                   

Hydra

                   (Image credit goes to Wikimedia)

  Hydra is a fresh water animal living in ponds, lakes, rivers etc. Both jellyfish and hydra are the members of the same phylum the coelenterata (cnideria). Unlike the case of jellyfish there is no medusa_stage in the life cycle of Hydra, polyp is the mature stage. Hydra do not show any aging sign in their life. There are lot of stem cells in their body, these stem cells are capable of continuous self renewal. A special gene called FoxO (forkhead box O) is the secret behind this capability of the stem cells. 

    Conclusions

Many other living beings also showed anti ageing capabilities. Out of three above mentioned animals only Turriptosis dohrnii is widely accepted immortal animal. They have different stages in their life cycle, they are able to revert back from mature medusal stage to polyp stage. But the case of human is different, we don't have such life cycle, so we can't adapt such type of anti ageing mechanism. But the anti aging technic of Lobsters and Hydra are very hopeful for us. We need a thorough study about the mechanisms. Lobsters are producing enough telomerase enzyme, and constantly maitain the length of telomere, the result is no senescent cells in their body. Humans are also producing telomerase enzyme, but the production is limited to embryonic stage only, why this happening? What is obstructing to produce telomerase in elder stage?. In the case of Hydra a special gene called Fox O gene is the secret of it's immortality. But in the case of humans we have four foxO genes, foxO1, foxO3, foxO4 and foxO6, these genes are involved in apoptosis, metabolism, stress resistance, cell cycle arrest etc. why these genes are not helping our stem cells for self renewal? We don't know, or even we don't have much idea about the working of foxO gene in hydra but one thing is sure foxO gene is the secret behind the immortality of Hydra. We need more studies in this regard. 

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The Hallmarks of aging

What are The 9 hallmarks of Aging?

 Aging

According to the scientific world there are 9 reasons behind Aging, they are generally known as 9 Hallmarks of Aging. They are Genomic instability, Telomeres Attrition, Epigenetic Alteration, Loss of Proteostasis, Deregulated Nutrient Sensing, Mitochondrial Dysfunction, Cellular senescence, Stem cells Exhaustion and Altered inter cellular Communications.

genomic instability

Genome is the genetical codes present in organisms. In other words genome is the complete set of DNA present in a cell. Every cell has  copy of the DNA. Genomic instability is the result of high frequency mutations ( sudden changes ) Because of  these mutations chromosome May rearranged, sometime the sequence of nucleic acids  or even the chromosome number May changed,( the chromosome number of human is 23 pairs, or 46 ). 

Telomeres attrition

Telomeres are the tail ends of chromosomes, which act as protective caps. I already explained about telomeres in my post " The telomere theory of Aging". Telomere Attrition or telomere shortening is one of  the four primary Hallmarks of ageing. After each cell division telomere become shorter and shorter. When Telomere is too short the cell cannot replicate anymore, this type of cells that cannot undergo cell division,these cells are known as senescence cells. Human body is capable of  producing an enzyme called telomerase, which can extend the the length of Telomeres but unfortunately the production of telomerase is limited, but cancer cells are producing sufficient amount of telomerase, so they are immortal.

Epigenetic alteration

Epigenetic alteration is the structural changes happens in DNA. These changes are due to adding and removing of methyl (CH3) groups. Another reason for epigenetic alteration is the changes made to histones. Histones are a family of basic proteins that wrap around DNA strands. There are four types of histone,H2A,H2B,H3,and H4. Histones are positively charged and DNA is negatively charged, so histones neutralise  the charges in the DNA, In addition the  DNA become more tightly packed. When an epigenetic change that turn off a particular gene that associated with damaged DNA repair function, then an increased DNA damage will be the result.

Loss of proteostasis 

With increasing age, the quantity of mis folded proteins are increasing in our body, these proteins are useless and even toxic in nature. Normal proteins are in helical structure and soluble in water. With increasing age there will be a decrease in the synthesis of  protein in our body and at the same time an increase of misfolded proteins also noted, So body will face the deficiency of proteins in older age, the result is loss of muscle mass, weight loss, weakness and so on.

Deregulated nutrient-sensing

Nutrient sensing is the Cells ability to recognize and respond to nutrient such as glucose,lipids,fats, and other food particles. There are 4 pathways associated with nutrients sensing mechanism, they are mTOR pathway, Insulin and Insulin like growth factor (IGF-1),signaling pathway, Sirtuins pathway and AMP kinase  pathway.

mTOR (mechanistic target of rapamycin) network sense hormone signals, nutrients, regulate metabolic activities etc. This network associated with many biological processes including immune responses, autophagy,and other functions of mitochondria etc.Insulin and Insulin like growth factor(IGF-1) signaling pathway has very important role in growth, metabolism and fertility. Insulin  is a hormone produced by Pancreas which helps liver cells to store glucose in the form of glycogen. Insulin like growth factor (IGF-1) produced in in many organs but primarily in liver, structurally it similar to Insulin. IGF-1 signaling promote growth of most of all tissues in our body. Unfortunately IGF-1 signaling reduced with aging. Sirtuins pathway involved in the regulation of fats and glucose metabolism, circadian rhythm, inflammation etc. Sirtuins are actually Enzymes.                             AMPK pathway: adenosine monophosphate activated protein kinase ( AMPK) is an enzyme, where AMP( adenosine monophosphate) is also called as 5'-adenylic acid, and kinase is an enzyme. AMPK pathway sense the energy status of the body, and helps to produced etra energy when needed. AMPK produced energy by the oxidation of fatty acids and glucose present in our body ( especially in liver and muscles). In our body when ATP ( adenosine triphosphate) lost energy it converted to ADP. AMPK activated when ADP level is increased in the body.

Mitochondrial dysfunctions

Mitochondria is known as the power house of a cell. This tiny organelles produced more than 90 percent of energy needed for our body. With aging mitochondrial failure can be observed, it cannot meet the energy requirements of the body. Mitochondria has it's own DNA, called mtDNA. According to the mitochondrial theory of aging ,when we age mitochondria produced less energy and more ROS ( reactive oxygen species) and other free radicals, these free radical and other external mutagens damaged the mtDNA The mitochondrial theory of aging says that "the rate of oxidative damage to mtDNA primarily determines lifespan"

Cellular senescence

With increasing age  there is an accumulation of  certain cells in our body, which are permanently lost their ability to divide, these cells are called senescence cells . Human cells can divided only 50 times, after that it reached the state of senescence. After each cell division the length of telomere shorter and shorter. When Telomere become very short the Cell division is not possible, this is the reason for cellular senescence. Senescent cells produced an inflammatory immunosuppressive, and some harmful chemicals. These chemicals entered the neighbouring cells monophosphate activated protein kinase ( AMPK) is an enzyme, where AMP( adenosine monophosphate) is also called as 5'-adenylic acid, and kinase is an enzyme. AMPK pathway sense the energy status of the body, and helps to produced etra energy when needed. 

Stem cells exhaustion

Each organ and tissues in our body contains several stem cells which are being used to replaced old cells when they die. In addition Stem cells have many important functions, such as immune functions, blood production, and so on. The number of stem cells slowly decreased with aging, this is the reason that injuries in older people are  healing more slowly when compared with younger people. different types of stem cells are present in our body they are blood stem cells, neural stem cells, skin stem cells, epithelial stem cells, mesenchymal stem cells, etc.

Altered inter cellular communications

During aging communication between cells becomes more disturbed. cells communicate each other using chemical signals. These chemicals are basically proteins or other molecules. The chemicals used for communication are known as ligands. These chemicals messages are received by target cell using their specialized receptors, all the cells don't have such facilities. In a multicellular organism four types of chemical signaling are identified, they are paracrine signaling. ( communication between neighboring cells), endocrine signaling ( communication between distant cells), autocrine ( cell signaling for itself, internal use) and signaling by direct contact ( signaling from one cell to adjacent cell). Here you may have a doubt , signals from brain and spinal chord are electrical impulses, where we can include it, no doubt synaptic signals are also included in paracrine category.
When neurotransmitters reached at the receiving cell the receptors received, and it caused chemical changes inside the cell. When we age chemical message used for cell communications tends to become more inflammatory. There are many factors behind this inflammatory behavior of the body, but senescence associated Secretary phenotype (SASP) is an important reason.

Conclusions                            

Out of the above mentioned 9 hallmarks of aging the first described 4 of them, the genomic instability, telomeric attrition, epigenetic alterations ,and loss of proteostasis are said to be the primary cause of aging and the rest of them are the results of  these primary hallmarks. I am wondering to know that cancer cells are immortal, these are also human cells, but isolated from other cells,  because of DNA damage, they are able to resist apoptosis. Cancer cells produced excess telomerase, so telomere attrition not happen and they live longer, they not showing any hallmarks of aging. Why normal cells are restricted to produce telomerase? This question is for you, find answer and let me know

FAQ

1.whatAre the hallmarks of aging? 

Answer: there are 9 hallmarks of aging, they are, genomic instability, telomeres attrition, altered inter cellular communications, cellular senescence, mitochondrial dysfunctions, deregulated nutrient-sensing, loss of proteostasis, epigenetic alteration, and stem cells exhaustion. These biological features collectively contribute the aging process and related diseases.

2, what is genomic instability?

answer: because of high frequency mutations, chromosome may rearranged in some cases the sequence of nucleic acid or even the chromosome number may changed. This type of changes  leading to various cellular dysfunctions and contributing to aging and cancer

3.what are epigenetic alterations?

answer: epigenetic alteration is the structural changes happened in D.N.A, these changes happened because of adding and removing of methyl group, another reason is the changes made to the histone, that seen as a wrap around D.N.A strands. these changes disrupt normal cellular functions and leading to aging.

4.what is the loss of proteostasis?

answer: decline in the ability of protein homeostasis is refers as loss of proteostasis, accumulation of misfolded and damaged proteins are the reason behind it. which can impire the normal cellular functions and leading to aging

5.how do deferent hallmarks of aging interact with each other?

answer: genomic instability can lead to epigenetic alteration, mitochondrial dysfunction is another example, which is the result of interaction between different hallmarks. this interplay can accelerate aging

6.can we control hallmarks of aging by changing lifestyle?

answer: yes you can control it by having balanced diet, regular exercise and adopting stress management techniques to a great extend.

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Old man + O2 = Young man

Hyperbaric Oxygen Chamber

Cellinsight.online Everything about human ageing and related diseases

Old man + O2=young man

     " Old man+O2=Young man" don't laugh I am not kidding you, this is the result of a new research conducted by Scientists from Tele Aviv University and Shamir Medical Center in Israel recently, and published in Aging magazine on 18th november 2020. The scientists claimed that they have managed to reverse the Aging.

The scientists used Hyperbaric Oxygen chamber for conducting this experiment. The treatment inside the hyperbaric oxygen chamber is known as hyperbaric Oxygen therapy (HBOT). They selected 35 people who where above 64 years of age. Pure oxygen supplied to them inside the chamber, at various atmospheric pressure, They were treated inside the chamber for 90 minutes a day and five days a week, the treatment continued for 3 months. The result was mind blowing, the researchers found that the cellular level changes of the participants were equivalent to how they where at 25 years back. The length of telomeres increased by 20-38% depending on different types of cells in the body. The senescence cells were also reduced 11-37%. Both Telomere shortening  and accumulation of Senescence cells are said to be two major Hall marks of Aging.

What is Hyperbaric Oxygen therapy (HBOT) ?.

Hyperbaric Oxygen therapy is a special type of treatment commonly used to treat many conditions such as carbon dioxide poisoning, healing of diabetic foot wounds,infection and injuries of bones, injuries to skin or soft tissues etc. Inside the chamber a patient is under an increased atmospheric pressure, where he can breath pure oxygen at 1.5-3,time higher than normal atmospheric pressure. When  received adequate amount of oxygen throughout the body, the body uses its own natural power to  promote healing process. HBOT can neutralise the toxins produced by certain bacteria, and also it increase the ability of WBC (white blood cell) to find and destroy foreign bodies. Also the therapy is useful for the formation of new skin cells, formation of new connective tissues, new blood vessels, production of vascular endothelial growth factor etc.

Telomeres

 Telomeres are the tail end  of chromosome, it act as a protective cap. In each cell division Telomeres are unable to be fully copied, so the Telomeres become shorter and shorter. In human being a cell can divided only 50 times before the Telomere become too short.

Senescence

When Telomere become too short a cell cannot divided any more,it enter the state of senescence. With increasing age,there is an accumulation of senescence cells in our body. These cells are said to be aged but they are metabolically active. It is difficult to repair a defective tissue if there is a large number of senescence cells are present.

Conclusion

"Aging is yet another disease" many scientists are still believing this.  I think Israeli scientists proved that the deficiency of Oxygen is the main reason for this disease by their HBOT experiment. What they did, they allowed the selected people to breath oxygen 1.5_3 times higher than normal pressure for some time period, that's all. Then they observed that the length of telomeres increased in each cell including senescence cells. You know if you removed all senescence cells from your body,  that itself will increase your life expectancy considerably. 

Here a common question is arising, why our body cells are not getting sufficient Oxygen from our normal breath ?, I think any one or more of following reasons should be behind it,

1. May be the atmospheric O2 level is not            enough because of pollution,deforestation      etc

2. May be our lungs are not able to absorb          enough Oxygen when we breath 

3. May be Our blood circulation is not                   enough to reach every tissues and cells

4.   May be our hemoglobin level is not              enough to transport O2 to each and                  every  part of the body.

      What is your opinion? Let me know.

    I hope the researchers find it very soon.

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Apoptosis and Necrosis, are they acceletate aging?

Cellinsight.online Everything about human ageing and related diseases

Apoptosis and necrosis are they accelerate aging?

apoptosis

Apoptosis is programmed cell death. Apoptosis is a Greek word means "falling off".In a multicellular organism if cells are no longer needed,or it's DNA damaged and cannot be repaired,then the cells commits suicide by a process called programmed cell death or the Apoptosis. In human beings billions of cells die in bone marrow and intestine every hour .since 19th century scientists noticed and described about apoptosis but a clear definition was given by John Foxton Kerr at the university of Queensland in 1972.Later Hovitz,Sydney Brenner,and John E Samson identified the genes involved in apoptosis. In 2002  they got Nobel prize in medicine 

Apoptosis and Necrosis

In our body,cells are produced by cell multiplication (mitosis) and the apoptosis is used to the destruction of cells. Around 100,000 cells are produced in our body per second and approximately same number of cells die by apoptosis. Apoptosis generally used during embryonic stage to eliminate unwanted cells, for example the cells between fingers and toes are removed by apoptosis in embryonic stage. Half of  the neurons that are created initially will die in later stages when adult brain is formed. Initiation of Apoptosis and it's completion is within 2-3 hours, within this time period the cells also removed,so the researchers facing challenges to study much about this process

Apoptosis is initiated by caspases. Caspases are any of the  family of  intra cellular proteases , which are synthesized inside the cells. They are present in the cell as inactive precursors or procaspases. During apoptosis these inactive procaspases or precursors activated by proteolytic cleavage by another member of caspase family. There are two types of caspases,the initiator caspases and the effector caspases, the initiator caspases are caspase 2,8,9,10,11,12 and effector caspases are caspase 3,6,7. Internal and external stimuli can trigger apoptosis. There is two well known apoptosis pathways which are the intrinsic and extrinsic pathways. Both intrinsic and extrinsic pathways are doing the same work that activate the effector capsases (caspase 3,6,7).The only difference is that caspapase 9 used to activate effector caspase in intrinsic and caspase 8, used in extrinsic pathway.

Extrinsic pathway initiated when death inducing signalling complex formed in the cell surface. These formation happened when death ligard bonds with death receptors. Later the signalling complex force to cleave  procaspase 8 and caspase 8 released to cystol. It act on effector caspases.

During apoptosis a cell undergone a series of changes,such as cell shrinkage, cytoplasm became dense,chromatin condensation (pyknosis),and DNA fragmentation (karyorrhexis).Irregular buds(blebbing) can be noticed on cell membrane, later membrane protrusions and finally the cell breaks apart into apoptosis bodies and adjacent phagocytic cells engulfed it

Necrosis

Necrosis is unplanned cell death,it may be due to lack of blood supply, infection, trauma,poison or any other reason. Necrosis starts with cell swelling,chromatin materials gets digested,loss of plasma membrane integrity, cell organelles broken down completely and finally, the cell lyses.

Aging and apoptosis

During aging it is noted that the size of muscular fibers are reduced and complete loss of some fibers. This condition his called sarcopenia. It is assumed that abnormal signaling of apoptosis and and mitochondrial dysfunction are the reason behind it,the exact reason remain obscure.

Experiment conducted on old rat shows  that significant increase in cell death,bcl-2 and capsase-3 are detected in extrinsic tongue muscles,and reduction in muscle fiber number. Scientists observed that old mitochondria produced more oxidant than energy 

Aging and necrosis

Old mitochondria produce more oxidants than energy(ATP). Apoptosis is an energy depend mechanism,because of the deficiency of ATP in olden age apoptosis decreased and the necrosis mechanism increased. we know that necrosis not need any external energy. The bad effect of necrosis is that it release the product of cell death in an uncontrolled way in to the intracellular space,and resulting damages to the surrounding tissues.

Conclusion

In order to maintain physiological, immunological, and biochemical functions effectively in our body, creation of new cells and destruction of old and damaged cells are necessary. Apoptosis and Necrosis are involved in this purpose, but unregulated Apoptosis can hurt the entire body. In old age apoptosis causes several damage to brain, intestine,  cardiovascular systems, prostate gland immune system etc. Increased programmed cell death has been observed in certain neurodegenerative diseases such as Huntington's disease ,Parkinson's disease,etc. many neural cells might die because of it's action, unfortunately neural cells cannot undergo cell division( mitosis) .We don't have much knowledge about the action of programmed cell death(PCD) in old age, in the mean time a number of researches going on, and this is an excellent subject for new researchers and one who looking for a Nobel prize.

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