The three barriers to unlimited life are diseases, accidents, and aging. Until we control aging, we
live longer principally by conquest of diseases. The top barriers to long life are (1) cardiovascular
disease, (2) cancer, (3) stroke, (4) chronic lung disease, (5) accidents, (6) Alzheimer's disease, (7)
diabetes, and (8) pneumonia/influenza. Researchers are progressing against these and many others,
and.each advance raises our life expectancy.
CARDIOVASCULAR DISEASE: There is great progress in prevention and treatment. Not
smoking, exercise, healthy diet, no obesity, annual medical exam, statins, aspirin, and medical
together have eliminated more than 80% of cardiovascular disease deaths. By 2002, deaths
from cardiovascular disease were 52% of 1970's level.
This reduction extends life expectancy 9
years. A 35 year-old can expect to live to age 87, and a 65 year-old to age 91, from prevention
of cardiovascular disease.
Recent Advances:
1. Sundaresan, N.R., and coworkers, The  Sirtuin SIRT6 blocks IGF-Akt signaling and development
of cardiac hypertrophy by targeting c-Jun.
(Nature Medicine, November, 2012). ISIRT6 has been
shown to have anti-aging properties. We now show that SIRT6 is low in failing hearts. In experiments,
additional SIRT6 protects mice from heart failure by suppressing c-Jun.
2. Song, K., and coworkers,
Heart Repair by Reprogramming Myocytes with Cardiac Transcription
. (Nature, 485, May 31, 2012). The adult mammalian heart has little regenerative ability
following injury. Cardiac fibroblasts are the majority of cells in the heart. Treatment of fibroblasts with
transcription factors GATA4, HAND2, MEF2C, and TBX5 together reprogram these cells into
cardiac-like myocytes, and restore normal heart function.
3. Bibbins-Domingo, K., and coworkers,
Projected Effect of Dietary Salt Reductions on Future
Cardiovascular Disease.
(New England Journal of Medicine, January 20, 2010). Modest reductions
in dietary salt could substantially reduce cardiovascular events and medical costs and should be a
public health target.
CANCER: Cancer is the second-highest barrier to longer life. While deaths from cardiovascular
disease dropped sharply from 1970 to 2002, deaths from cancer decreased only 3%. For men,
cancer's leading killers are (1) lung, (2) colon, (3) prostate, (4) pancreas, and (5) leukemia. For
women, it's (1) lung, (2) breast, (3) colon, (4) pancreas, and (5) ovary. We can prevent 95% of lung
cancer by not smoking. Daily aspirin prevents 40% of colon cancer, and statins prevent 47%.  Annual
medical exams are vital because early detection often permits successful treatment. Together, not
smoking, daily aspirin, statins, and medical exams can prevent 65% of cancers.
This can extend life
expectancy 6 years beyond that from preventing cardiovascular disease. A 35 year-old who
prevents cardiovascular disease and cancer can expect to live to 93 and a 65 year-old to 97.
Recent Advances:
1. Gaziano, J.M., and coworkers, Multivitamins in the Prevention of Cancer in Men. (Journal of the
American Medical Association
, November 14, 2012) In a large prevention trial of male physicians,
daily multivitamin supplementation modestly, but significantly, reduced the risk of all cancer.
2. Klein, E.A., and coworkers,
Vitamin E and the Risk of Prostate Cancer. (Journal of the American
Medical Association, 306, October 12, 2011
). In a study of more than 35,000 men, vitamin E, alone
or in combination with selenium, increased the occurrence of prostate cancer.
3. Nielsen, S.F., and coworkers,
Statin Use and Reduced Cancer-Related Mortality. (New England
Journal of Medicine, November 8, 2012
). Statin use is associated with a roughly 15% reduction in  
cancer-related mortality.
4. Evans, J.M.M.,
et al., Metformin and Reduced Risk of Cancer in Diabetic Patients. (British
Medical Journal, April 22, 2005).
Metformin significantly reduced the occurrence of cancers in
diabetic patients.

5. Cuzick, J., and coworkers, Estimates of Benefits and Harms of Prophylactic Use of Aspirin in the
General Population
. (Annals of Oncology, August 5, 2014). Aspirin, in daily doses of 75-325 mg,
confers a 7-9% reduction in cancers after three years of use.

CHRONIC LUNG DISEASE: This third-highest barrier to longer life is easily prevented, since 85%
is caused by smoking. The remaining 15% is from air pollution and other causes.
Preventing chronic
lung disease extends life expectancy a year beyond that from preventing other diseases. This
raises life expectancy of a 35 year-old to 96 and a 65 year-old to 100.
Unfortunately, foolish
people continue to smoke and deaths from chronic lung disease have doubled since 1970.
Recent Advances:
1. Tashkin, D.P., and coworkers, A 4-Year Trial of Tiotropium in Chronic Obstructive Pulmonary
(New England Journal of Medicine, October 9, 2008). In patients with COPD, tiotropium
therapy resulted in improvement in lung function and quality of life.
STROKE: The fourth highest barrier to longer life can be mostly avoided by not smoking, exercise,
diet, avoiding obesity, annual medical exam, cholesterol-lowering drugs, aspirin, and hypertension
control. The greatest advance in treatment is use of a clot-buster drug to treat the 2/3 of strokes
caused by artery blockage.
Together, these actions can extend life expectancy 2 years beyond that
from preventing cardiovascular disease and cancer. This raises life expectancy of a 35 year-old
to 95 and a 65 year-old to 99.
Since 1970, deaths from stroke have decreased by 63%.
Recent Advances:
1. Chen, P. and coworkers,  Inosine Induces Axonal Rewiring and Improves Behavioral Outcome
after Stroke.
(Proceedings of the National Academy of Sciences, June 23, 2002). Giving inosine to
rats, after a stroke, induced brain rewiring and recovery.
ACCIDENTS: The fifth highest cause of death can be largely avoided by careful driving and care in
daily activities.  
ALZHEIMER'S DISEASE: Incidence of Alzheimer's, the sixth leading cause of death, rises after age
65. More than 30% of 90 year-olds have it. Today, there is no cure. In Alzheimer's disease, masses of
two proteins, tau and beta-amyloid deposit in brain cells. Tau occurs in normal cells. The culprit may
be beta-amyloid. It destroys brain cells, condenses into clumps, and causes tau to form tangled
masses. Rise in beta-amyloid in brain correlates with loss of brain function. Beta-amyloid is formed
when two secretase enzymes snip it from a larger protein that is a normal part of cell membranes.
Prevention. Ibuprophen, Exercise, Statins, Curcumin, and Resveratrol have been reported to
prevent Alzheimer's or prevent accumulation of beta-amyloid
Treatment. If you can't prevent Alzheimer's Disease, Donepezil (Aricept) slows its progress.
Recent Advances.
1. Nagahara, A.H., et al., Neuroprotective Effects of Brain-Derived Neurotrophic Factor in Rodent
and Primate Models of Alzheimer's Disease.
(Nature Medicine, 15, February 8, 2009) When given
after disease onset, brain-derived neurotrophic factor (BDNF) reverses effects of Alzheimer's disease
in rodents and primates, suggesting possible therapeutic use against Alzheimer's Disease.
2. Ono, K.,
et al., Effect of Grape Seed-derived Polyphenols on Amyloid beta-protein Self-assembly
and Cytotoxicity.
(Journal of Biological Chemistry, 283, November 21, 2008).  Grape seed
polyphenolic extract is a potent inhibitor of amyloid formation and is also cell-protective. It may be a
potent therapeutic agent against Alzheimer Disease.
DIABETES: The seventh-highest barrier to longer life has two forms. Type I diabetes can't be
prevented or cured today. Victims require insulin and careful diet management. Type 2 diabetes,
which is more than 90% of all diabetes, can often be prevented by diet, exercise, weight control, and
drugs. Men with Type 2 diabetes cut in half their chance of death from diabetes if they exercise for 30
minutes per day. Obesity is a huge cause of Type 2 diabetes, yet two thirds of adults are overweight
or obese. As a result, diabetes has risen 45% since 1987.
Prevention or successful treatment of
diabetes extends life expectancy a year beyond that from preventing other diseases.
Recent Advances:
1. Zhou and coworkers, In Vitro Reprogramming of Adult Pancreatic Exocrine Cells to Bold Beta
. (Nature, Published online August 27, 2008).  By re-expressing three transcription factors in
vivo, pancreatic exocrine cells were converted to cells with that produced insulin and were structurally
like islet beta cells.
2. Tateishi, K., et al.,
Generation of Insulin-Secreting Islet-like Clusters from Human Skin Fibroblasts.
Journal of Biological Chemistry, 283, November 14, 2008).  It is now possible to convert adult skin
fibroblasts into functional pancreatic-like cells. This offers a potentially patient-specific treatment for
the many people suffering from diabetes.

3. Scarmeas, N.,
et al., Physical Activity, Diet, and Risk of Alzheimer Disease. (Journal of the
American Medical Association, 302, August 12, 2009).
Higher Mediterranean diet and higher
physical activity were independently associated with reduced risk of Alzheimer disease.
PNEUMONIA: The eighth-ranking killer can usually be prevented by an immunizing injection,
but many people don't get the injection. Even if pneumonia develops, physicians can often
treat it successfully with antiviral drugs, but some persons don't realize that they have
pneumonia, and they die. Immunization extends life expectancy a year beyond that from
preventing other diseases.
LIFE EXPECTANCY: Persons who use all preventive and therapeutic measures against disease
can have a life expectancy of 98-102 years. Since not everyone does this, highest life expectancy
today is 80 for men (in San Marino) and 86 for women (in Japan). According to the World
Health Organization, the United States ranks 33rd in the world with life expectancies of 75 for
men and 80 for women. Most nations ranking above the United States have government
insurance coverage for all citizens, while America limps along with private insurance that
millions of Americans cannot afford.

12 November 2014
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