|PROGRESS TOWARD CONTROL OF AGING
Even if we conquer disease, we will not live indefinitely, because aging steadily lowers cell and body
functions until it kills us. Although the world is full of charlatans who claim that they can stop us from
aging, there is no evidence today that any substance can stop, or even slow, human aging. This does not
mean that science will never stop our aging. It will, and people who claim that control of aging is
impossible are talking nonsense. Control will come, but how soon depends on how soon we understand
aging and develop drugs to stop it.
What is aging? Your body is composed of millions of cells that keep you alive and active. Some cells can
replace themselves, but many cannot. Over time, those cells deteriorate to the point where they cause a
tissue or organ to fail. Sometimes an organ can be repaired or replaced, but when enough failures occur
(or a vital organ fails), we die. A good analogy is your automobile. When you drive it new from the dealer,
all systems work well. If you do preventive maintenance, the car will run for a long time. But as time goes
by, components wear out and fail. You take the car to a garage and replace defective parts. As the car
gets older, more components wear out. This is aging and is true with your body. As we age, we need to
replace or repair worn-out organs and tissues.
What causes aging? Our cells are made of several thousand different kinds of proteins. (We are walking
blobs of protein.) They are the structure of cells, and they are the many machines inside cells that keep us
alive. Proteins are long chains of amino acids folded in unique ways. The trouble is that wear causes the
chains to unfold, and unfolded proteins stop working. Young cells can replace the unfolded proteins, but
old cells cannot. Some scientists proposed that oxidizers wreck proteins, but research shows that
antioxidants do not stop us from aging and do not extend life.
Genes may control aging and life span. Some families pass on the trait of long life to generation after
generation. In laboratory animals, mutation of certain genes extends life span two to five times. These
genes limit life, so blocking their action extends life. Similar genes occur in humans. These genes
probably block the action of enzymes that repair damaged proteins or DNA. If we develop drugs that block
life-limiting genes to give comparable extension of human life, it could give healthy people a life span of
500 years or more. Researchers are working on these genes.
Telomeres may also be involved in life span. Telomeres are strings of special DNA at ends of
chromosomes. Each time a cell divides, it shortens the telomeres. As they shorten, the cells exhibits the
deterioration of aging. An enzyme, telomerase, can restore telomeres. But when a cell matures,
telomerase switches off. If we can reactivate telomerase, an aging cell may become a young cell, but if
telomerase is unchecked, it makes cells continue to divide to form a cancer. For telomerase to prevent
aging, we need a drug that causes telomerase to stop aging, but not cause cancer.
If research on life-shortening or life-extending genes finds drugs that control these genes, we may be
able to prevent aging. The same may be true for drugs that control telomerase. For now, we may slow
aging by preventive maintenance and repair with drugs, organ replacement, and stem cells.
The question is not whether we will conquer aging. The question is when. In Hello Methuselah, I
projected, from the rate of research progress, that we will begin to control aging by 2030 and control it by
2050. It is a bright future.
Perez, V.I., et al., Protein Stability and Oxidative Stress are Determinants of Longevity in the Longest-Living
Rodent the Naked Mole-Rat. (Proceedings of the National Academy of Science, U.S,, 108, March 3, 2009). Compared
with mice (maximum lifespan 3.5 years), the mole-rat (maximum lifespan 28.3 years) has less oxidative damage to its
proteins, less protein unfolding, and faster destruction of inactive proteins. This indicates that maintenance of protein
integrity by rapid replacement of inactive proteins is essential for long life.
Minor, R.K., et al., SRT1720 Improves Survival and Health-span of Obese Mice. (Scientific Reports, 1, August 18,
2011). SRT1720 is a synthetic compound that extends lifespan in lower animals. It also improves health in obese mice
and extends mean lifespan by 44%. It also demonstrates the feasibility of designing molecules to extend lifespan.
Harrison, D., et al., Rapamycin Fed Late in Life Extends Lifespan of Heterogeneous Mice. (Nature, July 8, 2009).
Rapamycin given to elderly mice extended lives an average of 9% for males and 14% for females.
DePinho, R.A. and coworkers, Telomerase Reactivation Reverses Tissue Degeneration in Aged Telomerase
Deficient Micex.. (Nature, 469, January 6, 2011). In telomerase-deficient mice, when telomerase is reactivated by a
inducible telomerase, it not only stops deterioration of cellular functions, but also reverses the degeneration.
Alavez, S., et al., Amyloid-Binding Compounds Maintain Protein Homeostasis During Ageing and Extend Lifespan.
(Nature, 472, April 14, 2011). Exposure of adult Caenorhabditis elegans to the amyloid-binding dye Thioflavin T
profoundly extended lifespan and slowed ageing.
Fontana, L., et al., Extending Healthy Life Span - From Yeast to Humans. (Science, 328, April 16, 2010). Mutations
or drugs (such as rapamycin) extend lifespan ten-fold in yeast and Caenorhabditis worms, 60-70% in Drosophila, and
30-50% in mice. In these cases, the mutation or drug affect two gene pathways. The effect of rapamycin is not yet
known in monkeys or humans, but it may have similar effects.
Olnishi, M. and Razzaque, M., Dietary and Genetic Evidence for Phosphate Toxicity Accelerating Mammalian Aging.
(FASEB Journal 10, 1096 2010). In klotho mice, low phosphate slowed aging, and high levels accelerated it.