Designed to Last: Re-Engineering Humans

The magazine The Scientist, recently asked experts across various fields to re-engineer humans...to imagine that they were tasked to design humans to last rather than wear out and expire after only a few decades. What would they do differently? The resulting article, What if Humans were Designed to Last? is a fascinating read.

Along with admiration for the intricate and complex mechanisms that provides our cells with "nearly flawless surveillance, maintenance, and repair capabilities," the article also points out that "subtle changes and imperfections at every level of biological organization give rise to the diseases and disorders associated with aging and impose limits on the duration of life."

Evolution, for all its impressive powers to build such a complex system as the human species, is not design. Were the "molecular, cellular, and genetic machinery used to conceive, develop, and operate a human" the product of design rather than evolution, we would be different and look different.

Troublesome Cellular Obsolescence

Two kinds of cells that are particularly limiting to human longevity, neurons and muscle fibers, stop replicating past the growth/development stage. John Q. Trojanowski of the University of Pennsylvania discusses his fix:

An improved system to fold proteins and destroy unwanted proteins could drastically reduce the propensity for aggregation. Perfecting the physiology of chaperone proteins and improving the efficiency of lysosomes, proteasomes, and all the enzymes that eliminate the accumulation of disease-causing proteins would significantly reduce the likelihood of these diseases occurring. However, this fix wouldn't address neurological damage resulting from head trauma or stroke. A simple, cell-for-cell replacement model of neurogenesis might provide a more elegant solution. If a cell dies, a population of adult neural stem cells would quickly replace it.

Michael G. Bemben of the University of Oklahoma addresses the loss of muscle mass that comes with aging and creates many associated problems such as decreased basal metabolism and diminished postural reflex. His fix:

If loss of neural innervation to the muscle fiber is the primary cause for the loss of muscle mass, then muscle fiber number could be maintained as long as neural integrity is stable. In the brain, it appears that humans have roughly four-fold neuronal redundancy. In most people, as many as 30% of the cerebral neurons are lost due to wear and tear of normal life, but far less than the approximately 80% reduction necessary to produce clinical symptoms. One way to ensure an adequate number of functioning motoneurons would be to build a similar redundancy into the anterior or ventral horns of the grey matter in the spinal cord.

Radicals Shouldn't be Free

Another significant perpetrator of biomolecular damage are metabolic free radicals. The accumulation of unrepaired damage over time has been "prominently implicated in the aging process itself." Bruce Carnes comes up with this solution:

The solution to this problem must be systemic. While natural antioxidants are produced endogenously and occur in food, more powerful antioxidants also exist, such as amifostine (WR-2731), a radioprotector compound produced in the laboratory and used to ameliorate damage caused by radiation therapies. In addition, they tend to concentrate within the mitochondria where metabolic free radicals are produced, and they adhere to nuclear DNA. The latter attribute is significant: As it increases the structural stability of the DNA, it may also slow the cell cycle. If a gene to produce such compounds were introduced into the mitochondrial genome, the rate of aging should be slowed, and cancers should be reduced or delayed along with all other degenerative diseases that free radicals cause.

Can You See Me Now?

Scientists have long been aware of some "engineering flubs" in the human eye which are implicated in accumulated damage, resulting in the fact that more than 25 percent of individuals over 75 report vision impairment even with corrective lenses. Bruce Carnes on this problem suggests "engineering a photochromic cornea. A biomolecule with the same properties as silver halide and other materials used in so-called Transitions lenses would darken in the presence of UV light and protect the lens and retina."

Clearing the Choloesterol

Today's diet, heavy in animal fats and processed foods, creates excess low-density lipoprotein in the blood, which is believed to cause the buildup of plaque along the walls of our arteries. The narrowing and blocking of our arteries due to the buildup of plaques, in turn, causes heart disease and stroke. P. Michael Conn of the Oregon National Primate Research Center suggests this fix:

While enhancing the systems to reduce serum cholesterol levels seems attractive, the extra enzymatic activity required to process these lipids would likely necessitate a substantial size increase in what is already the body's largest internal organ, the liver. So, the best solution is a functional one: Coat the entire vascular system with a Teflon-like surface. Polytetrafluoroethylene is inert, has no net charge, and has the lowest friction coefficient of any known solid. A biomolecule with these properties, if expressed on the surface of endothelial cells lining the vasculature, would greatly reduce plaque buildup.

Coming Down to Molecular Level

"Age changes result from the increase in molecular disorder that, after reproductive maturation, slowly begins to exceed the capacity for repair, turnover, and synthesis of biomolecules. The very systems that are engaged in repair, turnover, and syntheses are themselves subject to randomly accumulating errors." To solve this problem, Leonard Hayflick of the University of California, San Francisco recommends:

Developing a perfect human being, built to live a life that is longer and healthier than what is experienced now, would simply require that all processes designed to maintain, turn over, or repair proteins, lipids, carbohydrates, or nucleic acids be carried out with near-perfect fidelity. With this ability in place, age changes and the consequent vulnerability to age-related pathology would decrease to the vanishing point.

We can continue to praise and extol the wonders of the human machine, while at the same time learn how to make it last longer. The ultimate goal: Prolonging human life indefinitely. See you there.