Appendix C: Strategies for Radically Increasing the Human Healthspan

Analysis of Causal Factors

The key to radical extension of healthspan lies in a careful analysis of the factors that cause aging in the first place. These factors fall into five broad categories (I draw heavily here on John Medina, The Clock of Ages: Why We Age, How We Age, Winding Back the Clock [Cambridge U. Press, 1996], ch. 13).

• Free radicals. Inside our body’s cells, as a by-product of the work that mitochondria do to generate energy, highly reactive molecules known as free radicals inevitably form. These molecules are like toxic waste, which our body works hard to dispose of properly. Whenever free radicals escape the cleanup mechanism, they travel about, wreaking havoc on any DNA molecules, proteins, and lipids they encounter.

• Sudden stressors. Our cellular biochemistry is continually being assaulted by a variety of factors, ranging from changes in temperature to radiation to pollutants such as heavy metals. The cell responds to these assaults by rapidly modifying the kinds of proteins it produces and the ways it delivers them – all in the interest of restoring its original state of functional equilibrium.

• Sugars out of place. Part of the normal functioning of cells requires the processing of glucose and other similar sugar molecules by a wide variety of proteins – a process known as glycosylation. If this process runs amok, the sugars fail to bond with their intended target proteins, and end up instead binding to other molecules that were not intended to receive them.

• DNA errors. Three types of mutations afflict DNA molecules: the deletion of a particular chunk in the sequence of chemical “letters;” translocations of nucleotide chunks from one part of the sequence to another; and point mutations of a single nucleotide. Not surprisingly, these alterations can carry grievous consequences, and the cell possesses robust repair mechanisms to make sure such mutations are avoided or undone whenever possible.

• Dysfunctional proteins. Healthy cells manufacture proteins in their cytoplasmic area, then dispatch them to their proper destinations where they begin performing their assigned functions. Defective or excess proteins are rapidly chopped up and “incinerated” by cellular cleanup mechanisms. When the cleanup mechanism fails, dysfunctional proteins accumulate in the cytoplasm, impeding its efficient performance.

Multi-pronged solutions

Virtually all the writers who address the issue of radical healthspan extension regard it as a multi-faceted problem requiring commensurately multi-dimensional solutions. You have to attack it from many angles at once. The best summary of such an approach is given by Aubrey De Grey in his book, Ending Aging: The Rejuvenation Breakthroughs that Could Reverse Human Aging in Our Lifetime (St. Martin’s, 2007), and on his frequently updated website, The SENS Research Foundation, online at:

De Grey’s approach to aging is summed up in the acronym, SENS: Strategies for Engineered Negligible Senescence. In De Grey’s view, human aging is the result of seven principal causal factors, each of which he believes can be reversed or mitigated through medical technologies that are either already in existence or under development today.

1. Cell loss, tissue atrophy, reversible through stem cells and tissue engineering.

2. Nuclear [epi]mutations, reversible through removal of telomere-lengthening machinery.

3. Mutant mitochondria, reversible through allotopic expression of 13 proteins.

4. Death-resistant cells, addressed through targeted ablation.

5. Tissue stiffening, reversible through specialized molecules and tissue engineering.

6. Extracellular aggregates, reversible through immunotherapeutic clearance.

7. Intracellular aggregates, reversible through novel lysosomal hydrolases.

De Grey offers a detailed explanation of each of these complementary strategies in his book and on his website, arguing that, taken together, they could already make a significant impact on human health today. He therefore urges his readers to exert pressure on their legislators to dramatically increase funding for research in these specific areas of biological science, gerontological medicine, and biotechnology.

The concept of Longevity Escape Velocity

“There is a threshold rate of biomedical progress,” argues De Grey, that will allow us to stave off aging indefinitely. … If we can make rejuvenation therapies work well enough to give us time to make them work better, that will give us enough additional time to make them work still better, which will … you get the idea. This will allow us to escape age-related decline indefinitely, however old we become in purely chronological terms. (Ending Aging, 330)

The idea here is that, if the science of aging continues to advance at its present rates, this may yield significant biotechnologies of rejuvenation over the coming half-century. The average human healthspan would then extend outward, along the lines described in Chapter 15. But once people start living healthy and vigorous lives of 160 years, the further advance of science, gerontology, and biotechnology during their long lifetimes could plausibly have allowed the creation of still more effective technologies of rejuvenation. Once these more potent rejuvenation therapies are applied, those same persons would presumably be able to live considerably longer than 160 years – during which time the science and technology of rejuvenation would continue to advance, thereby affording those persons still more significant extensions of healthspan. In this way, once a certain threshold has been crossed, it becomes plausible – in principle – for an individual to live indefinitely in good health. De Grey refers to this threshold with a metaphor from rocket science: longevity escape velocity.

Needless to say, the concept relies on a great many optimistic assumptions. There is no guarantee whatsoever that the advance of science and biotechnology during the coming century will yield ever-rising capabilities for human rejuvenation. But it does make for an intriguing hypothesis. If the hypothesis proves valid, someone born today could perhaps live long enough to cross the threshold of longevity escape velocity. That person could then in principle live on for hundreds of years – as long as the science of rejuvenation kept pace with her advancing chronological age.   Such at least is the dream of Transhumanists like Ray Kurzweil and Aubrey De Grey.

For further reading see:

  • Michael Rose, “The Metabiology of Life Extension,” in Steven Post and Robert Binstock, eds., The Fountain of Youth: Cultural, Scientific, and Ethical Perspectives on a Biomedical Goal (Oxford, 2004). Rose is a professor of evolutionary biology at U.C. Irvine, and a widely respected expert on aging.
  • Robert Arking, “Extending Human Longevity: A Biological Probability,” in Post and Binstock, eds., The Fountain of Youth. Arking is a professor of biology and gerontology at Wayne State University.
  • Richard Miller, “Extending Life: Scientific Prospects and Political Obstacles,” in Post and Binstock, eds., The Fountain of Youth. Miller is a professor of pathology at the U. of Michigan Medical School and Associate Director of the Geriatrics Center there.
  • John Medina, The Clock of Ages: Why We Age, How We Age, Winding Back the Clock (Cambridge U. Press, 1996). Medina is a molecular biologist, and affiliate professor of bioengineering at the University of Washington School of Medicine.
  • Aubrey De Grey, Ending Aging: The Rejuvenation Breakthroughs that Could Reverse Human Aging in Our Lifetime (St. Martin’s 2007). De Grey is a computer scientist at Cambridge University who has published extensively on the mechanisms of senescence in a variety of scientific journals. He is the most controversial (and visionary/eccentric) of the scientists who study radical healthspan extension, but his work has undeniably made a significant mark on the field.
  • Ray Kurzweil and Terry Grossman, Fantastic Voyage: Live Long Enough to Live Forever (Plume, 2005). I discuss Kurzweil and Grossman in Chapter 2.