Sipping from the fountain of youth

While it’s debatable whether most people would want to live to their 120th birthdays or beyond, it seems that medical discoveries and innovations – some of them Israeli – will significantly reduce the prevalence of chronic diseases in the coming years, from Alzheimer’s and Parkinson’s to diabetes and cancers. Nanotechnology, stem cells, organ replacement, more effective drugs and disease prevention will, according to some futurists, make the world a more crowded place and give funeral directors much more leisure time.

Although promoting longevity has fascinated science-fiction writers for centuries, Israeli physician, gerontologist and futurist Dr. Yaakov Ben-Shaul has written a new book on the subject in Hebrew. Titled Lazarus Long Ben 213: Refuat He’atid, Mehkerei Hoveh Vezikna (Lazarus Long is 213 Years Old: Medicine of the Future, Current Research and Old Age), the softcover, 172-page volume refers to the fictional eponymous character whom science-fiction writer Robert A. Heinlein made famous as “the oldest fictional member of the human race.” Methuselah was a youngster compared to Lazarus, who, according to the stories, lived for more than 2,000 years, passing from one world to another and often wishing he were dead.

However, Ben-Shaul’s otherwise fascinating science-based book – published by the international firm Contento De Semrik – was weakened, in my view, by the much-too-long chapter providing details about long-living science-fiction characters like the one in the title.

Mankind – at least in Western countries – has come a long way, as average life expectancy was around 45 at the beginning of the 20th century; by now, it has nearly doubled, thanks to improved medical care, antibiotics, vaccinations, better food and water supplies and prevention.

Yet chronic disease, aging and death have always been considered inevitable. Ben-Shaul, who interviewed leading physician researchers and scientists in Israel and abroad for his book, insists that a breakthrough in longevity will soon be upon us.

The 55-year-old author often cites with some ridicule the Health Ministry’s 2003 report and announcement in Jerusalem that “no breakthrough in extending life expectancy” is expected in the foreseeable future, even with today’s known methods of preventing death from diseases. The ministry issued the statement following discussions by medical experts whom the ministry and the Knesset Science and Technology Committee had brought together. The statement was meant to fight charlatanism, as many commercial interests have made baseless anti-aging claims.

But Ben-Shaul dismisses the report and statement for their too-comprehensive declaration that overlooks major scientific developments that were apparent even a decade ago.

It used to be thought that senescence was irreversible and inevitable. “Aging has indeed been forced on the human race until now,” writes the author. “But a careful examination of current Israeli research discloses that we are on the edge of a significant jump in lifespan and that there is a real potential that in a few years, the Western world will have the ability to delay dramatically the pace of aging.”

THE AUTHOR begins with a rather depressing list of what naturally happens to the human body as the years pass. Physiological changes include difficulties in walking due to damage to the skeleton, muscles and ligaments; a decline in hearing; possible weight loss and undernourishment; reduced supply of blood to the brain and loss of nerve cells; poor balance and falls; degeneration of the central nervous system; clogged blood vessels; increased blood pressure; and kidney damage, to name only a few.

Statistics from around the world show that the average person in the Western world takes 12 different kinds of medications daily, some of them unnecessary and in conflict with each other. As a result, a quarter of all hospitalized patients over age 80 suffer from significant side effects. Cognitive function usually declines, resulting in confusion if not dementia. Social losses and an end to employment promote depression.

He quotes Dr. Gary Sinoff of the gerontology department at the University of Haifa’s faculty of social welfare and health sciences as saying that instead of declaring a person “old” based on his or her chronological age, one should instead ask the person to fill out a two-part questionnaire with a total of 18 questions. They include whether he/she feels insecure going down stairs; has a problem driving; has to turn up the TV or radio to hear; avoids leaving the house for social encounters; has changed eating habits and lost weight; forgets finishing tasks or where he/she left objects; suffers from restless sleep; has trouble reading even with glasses; takes more than eight different medications, including food supplements; and is in regular contact with his/her family.

Ben-Shaul personally interviewed Prof. Moussa Youdim, the senior, Iranian-born Jewish neuropharmacologist at the Technion- Israel Institute of Technology who developed rasagiline (Azilect) – a drug that millions of people around the world take to slow the development of Parkinson’s and Alzheimer’s diseases.

Youdim, who has spent many years researching the deterioration of neurons, has proven that neurons are destroyed by “rust-like” oxygen free radicals, which cause the cells to “commit suicide” (a process known to scientists as apoptosis). The drug he developed slows the release of the enzyme mono-amine, which is involved in the oxidation processes in the brain and iron metabolism. A new drug he has worked on, ladostigil – which is now undergoing clinical trials – raises the level of acetylcholinesterase and is believed to reverse some of the damage of neuro-degenerative diseases.

A pathfinding step in genetics was James Watson’s and Francis Crick’s 1953 discovery of the double helix structure of DNA. In 1954, another major step was the first successful kidney transplant between identical twins. But as long as 80 years ago, Dr. Clive McCay and Mary F. Crowell at New York’s Cornell University discovered that severe calorie restriction – with consumption of vital nutrients – causes animals to live much longer. Ben- Shaul notes that such anorexia is not practical for helping humans to live longer, but it explains how two genes that serve as “gatekeepers” fight cellular senescence. The Human Genome Project that mapped out 25,000 genes by 2003 was also a major discovery that will extend life, he says.

The study of human embryonic stem cells (hESCs) that are capable of turning into virtually any type of bodily cells – an area in which Israeli researchers are prominent – will lead to major practical advances in the regeneration of malfunctioning tissues and even whole organs, the author continues. Every major medical research institution – including many in Israel – are investing brainpower and funds in basic and clinical work in the field of hESCs.

Commercial interests, including Israeli companies like Pluristem, have quickly identified the potential, sold shares on the stock market and registered patents for their discoveries. Patients with multiple sclerosis, type II diabetes and many other degenerative illnesses could benefit from hESC techniques.

Ben-Shaul also interviewed Dr. Arik Hasson, a leading Israeli scientist working for commercial firms on hESC applications. Instead of creating whole new hearts, he is working on producing cardiac tissue to replace dying or dead cells.

The July 1996 birth of Dolly, the domestic female sheep who became the first mammal to be cloned from an adult somatic cell through nuclear transfer (by Dr. Ian Wilmut at the Roslin Institute in Scotland), is the subject of many paragraphs’ worth of discussion.

The cell used as the donor for the sheep’s non-sexual cloning was taken from a mammary gland. But the explanation for the sheep’s premature death of progressive lung disease and severe arthritis in February 2003 was the fact that the original cell came not from the combination of ova and sperm, but from her mother’s somatic cell, which was already six years old.

The accepted theory is that Dolly’s telomeres – regions of repetitive nucleotide sequences at each end of a chromosome, which act as biological clocks to protect the end of the chromosome from deterioration – had shortened as she aged, and led to her death. Thus Ben-Shaul notes that promising research is expected to lead to protection of the telomeres, extending lifespans. Numerous startups that have focused specifically on telomere research exist around the world.

ADVANCES IN conventional medicine and biotechnology have included the development of tPA clot-busters to save ischemic stroke victims from paralysis and death.

But while this treatment dissolves clots, it can cause severe, even life-threatening side effects. So before it is injected, the patient must undergo an MRI scan to determine if it would be dangerous. In any case, the author warns, tPA is actually given to only 10 percent of stroke victims.

To fill this gap, researchers at Hadassah University Medical Center in Jerusalem’s Ein Kerem neighborhood conducted research into a synthetic alternative. The Thrombotech company based in Ness Ziona is now proceeding in developing an artificial peptide, THR-18, that binds with tPA, extends its period of efficacy and cuts its risky side effects.

Work on angiogenesis – the production of small blood vessels that provide an oxygen supply to metastasizing tumors – promises to reduce the death toll from cancer, Ben-Shaul continues.

Meanwhile, the Blue Brain Project – established in 2005 by the Brain and Mind Institute of the École Polytechnique Fédérale in Lausanne, Switzerland, with the intensive involvement of Hebrew University brain researcher Prof. Idan Segev – is working to create a synthetic brain by reverse-engineering the mammalian brain down to the molecular level. Headed by the Swiss institute’s director, Henry Markram, the project is expected to provide a biologically realistic model of neurons and eventually lead to the improved treatment of numerous brain diseases.

Maintaining good health and early screening for disease will be prominent in medical treatment of the future. The family physician will use robotics and computers before deciding on diagnosis and how to treat.

One’s personal genome will be combined with pharmacology to produce effective pharmaco-genetic care. And it won’t be science fiction, says Ben-Shaul, when nanotechnology creates a microscopic device that will “sail” through the bloodstream and catch and kill cancer cells, clean up cholesterol, test high sugar levels and find other dangers before they cause damage. Israeli scientists are prominent in this field as well.

There will also be robotic limbs for the physically disabled. Steve Austin, the bionic Six Million Dollar Man, will no longer be the stuff of imagination, and computers will make it possible for the limbless and paralyzed to function just by thinking.

Yet, for many years, it will probably be only the well off who benefit from these discoveries due to expensive healthcare costs; the Third World, surely, says Ben-Shaul, will not be able to afford it.

EXTENDING LIFESPANS will bring never-dreamed-of benefits, but is the world prepared for them? Retirement, leisure time, housing, food supply and many other aspects will be greatly affected.

The author ends the book with a chapter on psychology, depression and narrative gerontology. Individuals who live way beyond what they expected will need help to cope emotionally. They will need a future-time perspective instead of seeing their soon-approaching end. A biological and psychological age will replace their chronological age, and the best way to deal with this, Ben-Shaul concludes, is with “narrative treatment,” in which the individual maps out his past life and his future, open-ended expectations.

A longer life could be a dream for some and a nightmare for others – depending on how it is lived.