Death at the fundamental level

 

      Friends, A few months back I and my friend Abhishek Datta were having a discussion on ageing and death. As the discussion progressed we started talking about how the fundamental unit of life i.e a cell dies. How does a cell die naturally? What does ageing mean for a cell?

We did not have the answers to those questions then. So I decided to write a VERITAS on this topic.

        In this VERITAS we will not discuss how a cell may die from external factors: injury, predation etc. We will discuss how a cell in an otherwise harmless environment dies. How does it know when to die. And does it show visible signs of agening before dying?

        First thing to note is that cell death is important for the living being. A tadpole cannot become a frog till it sheds off its tail. So the cells in the tail have to die. A human foetus has tissues between the fingers and toes. The fingers and toes are webbed. For proper formation of fingers and toes it is important that the cells in the tissues between the fingers die. The formation of proper connections in the brain means that surplus neuron cells be removed. And the death of the animal itself would in some way be also related to the ageing and death of the cells that constitute it.

        Every cell is programmed to die. Animals are also programmed to die. We all die after a certain age. In the case of a animal the cause of natural death is the death of certain critical cells. So the death of these critical cells causes death of the animal. But what happens in the cell? What dies inside it? Nothing! The cell kills itself after a certain time. Cells are programmed to commit suicide. This is called Apoptosis.

So cell death by suicide is the starting point of all death. It is the fundamental unit of death.

        So cells maintain some sort of timers which tell them when to die.

These “timers” are called telomers. Telomers are strips of DNA at the end of chromosomes. Whenever a cell divides the telomers get shorter. After a number of divisions the telomers get very short and then they vanish. This tells the cell that it is time to commit Apoptosis. “Time is up. You are history.”

      The cell then starts the apoptosis program: cell junctions are disintegrated, cytoplasm is condensed. The cell shrivels up. Lumps of chromatin collect around the nucleus. The nucleus breaks up into several parts which are then eaten by neighbouring cells. The energy centres of the cell : mitochondria  are preserved till the very end. And this is because the cell needs energy to undergo the various stages of apoptysis.

So the cell uses its own energy and kills itself in a well programmed series of steps.

        Now a cell does not age in the normal sense of the term. So there is no difference between a cell that is young and one that is old. The only place where there is a difference between the young cell and an old cell is the length of telomers. But multicellular organisms are different. There are visible signs of ageing. How does that happen? That happens when cells in the animal start dying. For example a person in his thirtees may have some grey hair. That is a sign of ageing. That means that some of the cells responsible for colour of the hair are dead.

        So we see that cell death is a programmed well defined exercise.

Can it go wrong? Yes! Imagine this: something goes wrong in the cell that does not allow telomers to shorten. What will happen: the cell will divide forever without dying. This is cancer! A cell that protects itself from suicide is a cause of cancer. It keeps dividing forever and keeps passing on the “desire not to commit suicide” to its offspring. Some cancer cells have mechanisms of rebuilding their telomers so that they do not expire. Others have some sort of protective co vering over these telomers so that they are not reduced on cell division.

        The immune system also relies upon cell suicide to prevent infection in the body. The immune system cells(lymphocytes) make cells infected by viruses commit suicide. So the infected cells commit suicide and the viruses inside also die- end of infection. But some viruses know this trick and try to make the cell not commit autopsis! After the disease has been repelled the lymphocytes kill themselves by autopsis – they realize that they are no longer needed. Note that this autopsis is not timer based: it is event based. The lymphocites realize that they are no longer needed by the body(we have not studied this in detail in this VERITAS). But if there is a problem in the lymphocites mechanism of autopsis then they dont kill themseves but keep inducing autopsis in normal healthy cells. This causes autoimmune diseases like rheumatoid arthiritis. Autoimmune diseases are those in which the immune system works against the body instead of fighting external infections.

      So we see how important cell death is for the animal(or plant). But somehow we humans dont seem to come to terms with death. For us death is sometimes a reason for fear and sorrow. And we invent religions and things like heaven and hell and rebirth to come to terms to this reality. These religions are the religions of fear. If there is life then death must happen. A cell dies to improve the animal. The animal dies to improve the species. The species dies to improve life. The individual exists and dies for the improvement of life. The individual is a slave of Nature’s design. Nature does not exist to serve the individual’s foolish desires of happiness or immortality.

      Poets have always been obsessed with death. In the following poem Wordsworth writes about his sorrow at the fact that his little daughter is dead. One day the poet gets a pleasant surprise. He wants to share that with his daughter. But he then realizes that she is dead and cannot share the joy. The feelings of joy vanish and turn to feelings of sorrow:

      SURPRISED by joy–impatient as the Wind

        I turned to share the transport–Oh! with whom

        But Thee, deep buried in the silent tomb,

        That spot which no vicissitude can find?

        Love, faithful love, recalled thee to my mind–

        But how could I forget thee? Through what power,

        Even for the least division of an hour,

        Have I been so beguiled as to be blind

        To my most grievous loss?–That thought’s return

        Was the worst pang that sorrow ever bore,                

        Save one, one only, when I stood forlorn;

        Knowing my heart’s best treasure was no more;

        That neither present time, nor years unborn

        Could to my sight that heavenly face restore.

 

Kanwar

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  Go, wondrous creature! mount where Science guides:                 

  Go, measure earth, weigh air, and state the tides:                 

  Instruct the planets in what orbs to run,                          

  Correct old time and regulate the Sun;                             

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