WHY DO WE AGE? HERE ARE EIGHT REASONS WHY EXTENDED LIFE IS STILL A PIPE DREAM

I had a discussion with a colleague at a forum I attended.  He claimed it will be possible to extend human life expectancy so that we die at 120 or even 150.  Length of life is tricky because there are several life expectancies.  Our present mean life expectancy in the US for a newborn is about 85 years.  When I was born in 1931 it was about 65 years.  When my father was born in 1901 it was about 55 years.  For a baby born in 1776 it was about 35 years.  Most of that gain came from a reduction in infant mortality.  In 1776 about half of all babies died in their first year of life.  Pneumonia, gastrointestinal infections, and tuberculosis were the most common.  By 1860 public health measures were becoming standard.  After the germ theory of 1880 became widespread, pasteurization of milk, chlorination of water, and vaccinations became common.  Infants and children lived.   If we excluded infant mortality the differences in survival to old age are not profoundly different from biblical times (about 70 years) for most of human history until the twentieth century.  In that century antibiotics, antiseptic surgery, and numerous medical processes (hormones, blood transfusions, prescription medications for high blood pressure) could extend length of life. That is why a baby today can live to about 85 years. The maximum length of a human life, based on birth certificate evidence, is about 122 years. 

We have no problem on the causes of aging of the cars we drive. Every part of a car experiences wear and tear with usage, no matter how often we bring our cars in for servicing.  If we are foolish and don’t routinely service our cars they break down much faster. It could be problems with the engine, the transmission, the radiator, the electrical system, the body frame, or a rusting through or crystallizing of the metal components. No one would look for a single cause of what makes an old car on its last years of usefulness.  Yet many people like to seek a single cause of aging in all of cellular life.  At least eight major reasons have been identified on why we get old and die.  First, our DNA in our chromosomes undergoes breakage from background radiation, chemical agents we consume or inhale, or the by-products of our metabolism in our cells.  Chromosome breakage in dividing cells often causes cell death. Second in importance, our DNA is vulnerable to gene mutations arising from the same type of agents when they alter chemical components of the DNA in our genes.  We have repair enzymes to stop most of this damage which occurs every day of our lives, but as we age cells get less efficient and the damage accelerates.  Third the tips of our chromosomes are capped by telomeres.  Each time a cell divides the telomeres shorten. Human cells in tissue cell cultures can only divide about 30 times and they stop.  The one major exception to this is certain cancer cells which can keep on growing decades after the death of the person whose cells are in tissue culture.  Fourth, genes are temporarily turned on or off by coating with proteins or attachments of methyl groups.  This is called epigenetics. As we age different chromosomes get coated (methylated) and thus functions can shut down in those cells.  Fifth, our mitochondria are found in all our cells and they do the real breathing, taking oxygen brought from our lungs to our cells and they convert digested food into carbon dioxide and water and produce abundant energy molecules for other activities and generate the heat of our bodies.  They have their own DNA and the oxidative processes can severely damage their genes.  As we age our mitochondria are fewer in number and less efficient, which is one reason old people feel colder and have icy hands and feet.   Sixth our proteins as they are synthesized by our genes undergo folding.  In older people that process of folding becomes less efficient and the impaired folded proteins form tangles and this can lead to Alzheimer syndrome in some and diabetes in others as important proteins in the brain neurons or the pancreas are misfolded.  Seventh stem cells are used to regenerate red blood cells, white blood cells, the lining of our intestines, and several other issues that are subject to mechanical wear and tear.  As we age stem cells lose that capacity and become fewer in number so we wrinkle and our bones deform with aging.  The eighth reason why we age involves the communications from cell to cell throughout our bodies.  There is “cross-talk” locally by diffusion and cross talk at greater distances, especially by hormones.  These communications break down and become unreliable as our bodies age.

While some have argued that we are programmed to die, I favor the interpretation that , like old cars, we just wear out from these eight known processes of aging.  I am skeptical we can extend life to 120 years for the majority of adults without considerable years of ill health.  All eight of these processes need to be addressed and just having the right diet and the right exercise and right attitude is no guarantee for indefinite life extension anymore than the well pampered car can last forever if driven to work every day.  So far, I am 83.  The oldest person on my father’s side lived to be 93.  None of my maternal grandparents descendants has lived to be 90.  I’m not complaining.  Those 83 years have been filled with adventure, love, learning, and creativity.  I have also been lucky.  I have never been hospitalized as an inpatient for a major illness. But I know I am old.  

BLOG -- GETTING OLD –PAST, PRESENT, AND FUTURE

 All multicellular living things, plants and animals, have a life cycle.  The overwhelming number of species have sexual reproduction. Some organisms are relatively short lived.  A fruit fly lives about 55 days. Mice live about 2 years. Most organisms live about ten to twenty years. Humans are long lived and they live 70-100 years depending on where we live with outliers that reach 115 years. Galapagos tortoises live about 250 years.  Plants do better than animals.  Bristle cone pines live 4000 or more years.  Redwoods reach 3000 years.  There are cheater species like Norway pines that live at least 9000 years by sending out shoots from their roots to produce clones.  So the original tree might be long dead but its genotype keeps going through this budding and cloning process that supplements new offspring by the old fashioned way (fertilizing an ovule with a pollen grain in a flower).

The rule of life is that two gametes (for us, a sperm and an egg) unite to form a fertilized egg which forms an embryo which forms a newborn which matures through childhood to become a young adult, then a middle aged adult, and then a senescent adult who eventually dies. We know that as a life cycle. Humans are unusual among animals in having greater mobility (they spread around the world), an intelligence that aids their survival, and a culture that they can transmit orally, or in more recent times, by writing.

In the past 100,000 years of Homo sapiens as a species, half of that time we lived in Africa. About 50,000 years ago humans moved out of the Middle East and headed westward into Europe and eastward into Siberia  and what is mainland China and south east into what is now Indian and southeast Asia.  By 30,000 years they populated Australia and moved into the Pacific islands. By 15,000 years ago they crosses from Siberia into Alaska and moved south and East to populate the Americas. They still hadn't written anything.  They still hadn't built any cities.  They left their stone tools behind and occasional tools of bone and wood that lucked out and survived in caves and other debris relatively dry and free from decomposing bacteria.  By the time the first Americans were settling into the west coast of North America, the first farms were being developed in the middle east and Asia.  The first domesticated animals, especially cattle and sheep were being domesticated in the middle east.  The shift to agriculture led to unexpected outcomes.  It led to the birth of cities.  It led to the birth of written languages to allow trade to be recorded. It led to the development of scripture or religious writings about the gods they worshipped. It led to a rise in the world populations and humans could now be counted in a few millions around the world.

          That population size remained fairly stable with barely two children surviving to reproductive maturity in each family that began parenting. Births were numerous but survival was slim. Humans had not learned how to preserve food for lean seasons and years of extreme cold or heat or drought or floods.  They had not developed a system of waste disposal and hygiene to ward off infectious diseases. Few reached old age.  Most communities consisted of children and young adults. Imagine surviving today without sewage disposal, without antibiotics, without public health programs, without chlorination of water, without pasteurized milk, without immunizations against infectious diseases, without surgery, and without medications for failing organ systems. 

         The population of the world increased again as cities fused into nations.  The world population did not hit one billion until the industrial revolution when machinery improved farming, food processing allowed storage of foods, printed books on medicine and health informed physicians throughout Europe, and the rise of universities doing research allowed scholars to flourish. Even then, until the 1870s the chances of a newborn child living the first two years of its life, was only 50 percent.  Mean life expectancy was about 45. Two things happened in the last half of the nineteenth century that changed human population. The first was the germ theory that Pasteur, Koch, and Lister developed and promoted.  The second was the Public Health movement that Virchow initiated in Germany and exported to the industrialized world.  By the twentieth century a remarkable shift was occurring.  Children were almost guaranteed they would live to reproductive maturity. This in turn led to very large families of 5 or moiré children.  It led, in 1913, to the birth control movement through the efforts of Margaret Sanger. First the rich, then the middle class adopted it.  By the Great Depression of the 1930s the poor were also limiting family size to about two children. 

              In turn this shifted the world population.  In 1850 it looked like a pyramid with a base of lots of children and few old people at the top. At the close of the 20^th century it looked like a stele (think of Cleopatra’s Needle in Central park in New York City).  The number of children was barely more than replacement of those dying of old age.  That in turn had unanticipated outcomes.  The elderly depended on their children to support them. This did not change until the 20^th century when programs like social Security were introduced.  We pay taxes so that we will have a place live, food to eat, and medical costs taken care of as we get old.  Health care in the US was neglected until the late 20^th century when President Johnson got Medicare and Medicaid passed in Congress.  A more complete coverage of the poor and unemployed in the US was introduced by President Obama in this 21^st century.

              The trend to a shrinking base of young people will continue world wide.  It will lead to a world with more old people than young people.  In the US this will lead to the election of Representatives and Senators who will represent the interests of the old.  I predict this will happen about 2050.  I also predict that it will lead to a Department of Aging in the President’s cabinet.  I predict that this cabinet office will lead to more effective retirement investment.  It will lead to a change in health care delivery (salaried health workers instead of fee for service).  It will lead to the creation of a Domestic Peace Corps for and by the aged who will focus on the productive years of older citizens.  If the standard of the 20^th century was 65 at the time of retirement, today that means 25 more years of life after retirement.  How should one live?  What resources will there be for education, volunteer service to the neglected aspects of society, volunteer service to cut the costs of health, housing, infrastructure, and municipal; services.  That is where the pooled ideas and talents in a department of the Aging will be easily made known and many of them funded.

              In Biblical times 70 was the expected age of death for most people who survived childhood. There was no retirement.  In 1920 the expected age of death for most adults was 75 and retirement was about 65.  In 2015  it is still 65 for retirement but death is close to 90 in some industrialized nations.  Most of us will have 15 good years of those 25 years of retirement. It is those last ten years where the inevitable crumbling of our life cycle will take place.  Given our penchant for discontent, what would look like a fabulous blessing 200 years ago of human expectations will still be seen by many as not enough. Whether we master the tools to extend life expectancy farther, to slow down the aging process, or to fund our desires are beyond our capacities to predict accurately.  Fortunately, we can address the problems of our own generation and let us hope we will do so.