A Solution to Aging?

Pharmacy Times, Volume 0, 0

In a New York Times editorial severalyears ago, William Safire wrote anessay entitled "Why Die?"1 Accordingto the writer, nothing makes the weakstrong or the fearful brave as much asthe body's innate drive to stay alive. Hispoint was that the genetic clock is set torun no more than 120 years, althoughmany people would like to live muchlonger. A recent government report summarizedthe will to survive, noting thatthe inevitability of aging—and with it thespecter of dying—has always hauntedhuman life; and the desire to overcomeage has long been a human dream.2

This powerful inherent drive to stayalive has encouraged some pharmaceuticalcompanies to consider developing theultimate blockbuster drug—a so-called"antiaging" pill. A number of biotechnologyfirms already have begun the searchfor a chemical that would slow down theaging process or prevent cancer, osteoporosis,and heart disease. Studiesdesigned to show that a drug will retardaging, however, would be lengthy andlikely would last longer than the investigatorsthemselves. Because the FDA doesnot consider aging a disease, it may noteven permit such studies to occur.

Antioxidants

There are manufacturers of nutritionalproducts that already advertise theirantioxidant formulations as a means toretard aging. (Age retardation is the slowingdown of the biological processesinvolved in aging, resulting in delayeddecline and degeneration.2) These compoundsare alleged to work by combatingthe effects of free radicals and delayingthe decay of mitochondria,the organelleswithin the cell that convertamino acids, fatty acids, andsugars into energy. Freeradicals can disrupt proteinsynthesis and repair andcan cause minor errors inDNA replication. Whereasantioxidants may havesome health benefits forsome people, no scientificevidence exists to justifythe claim that they haveany effect on human aging.3

Hormones

It has long been knownthat endocrine factors areclosely tied to a number ofthe most prominent elementsof aging. Thus anumber of hormones havebeen touted as age retardants,including growth hormone,dehydroepiandrosterone,pregnenolone, testosterone,estrogen, melatonin, and progesterone.None has been proven to slow, stop, orreverse aging, however.4

Caloric Restriction

Since at least the mid-1930s, medicalscience has discovered that substantialreductions in the food intake of manyanimals can have a dramatic effect onlife span. In mice and rats, researchershave found that life span can be extendedby more than 30%. Studies also havefound similar extensions of life in a numberof other mammalian species, includingmonkeys.5 Caloric restriction in animalsreduces levels of insulin-like growthfactor 1, a protein, and prevents oxidativedamage to body tissues.

Although caloric restriction mightextend the longevity of humans, as itdoes in a number of animal species, nostudy in humans has proved that it willwork.3 Short-term trials now are beingconducted at the National Institute onAging in Bethesda, Md. Volunteers inthese trials have been on a stringent dietfor up to 1 year, while researchers monitortheir metabolism and other factorsthat could hint at how they are aging.

Telomeres

Telomeres are the repeated sequencesfound at the end of chromosomes thatshorten with increased cell divisions.There is evidence that telomere lengthplays a role in determining cellular lifespan in normal human fibroblasts andsome other normal cell types.6 Althoughtelomere shortening may play a role inlimiting the life span of certain cells, thereis no evidence that it plays a role indetermining human longevity.7

New Approaches

In a 2003 article in a major medicaljournal, 2 researchers reported on whatis apparently a more measured means toachieve an increased life span.8 Theirthought is to address or reduce risk factorsthat lead to heart attacks andstrokes in everyone aged 55 years andolder and everyone with existing cardiovasculardisease. This approach aims atextending life but not retarding aging.

There is a major difference, althoughthe results may appear similar. Lifeextension is an increase in the number ofyears that a person remains alive and isaccomplished by combating diseases ofthe aged or slowing down aging. Thetreatment consists of a once-daily"polypill," which contains a statin, 3blood pressure-lowering drugs (a thiazide,a beta-blocker, and an angiotensin-convertingenzyme [ACE] inhibitor); folicacid (0.8 mg); and aspirin (75 mg). Theresearchers estimate that the combinationreduces ischemic heart disease by88% and stroke by 80%.

In addition, the authors claim that onethird of the people over age 55 taking thispill would benefit, gaining on average 11years of life free from heart attack andstroke. The combination drug wouldlower 4 risk factors: low-densitylipoprotein cholesterol,blood pressure, platelet function,and serum homocysteine.

The authors admit that thepolypill may not be suitablefor some people. They notethat beta-blockers are contraindicatedfor asthmaticsand that some individualsare intolerant of aspirin.Monitoring for the effects ofstatins and ACE inhibitors also should beconsidered.

Even newer than the "polypill" conceptis the "polymeal." It includes 7 ingredients:dark chocolate, wine, fish, almonds,fruit, garlic, and vegetables. The componentscan be taken combined in a mealor individually at different times of theday. According to the authors of a recentarticle, the daily consumption of thesefoods would reduce cardiovascular diseaseby 76% and would result in anincrease of 6.6 years in total lifeexpectancy for men.9 The results shouldbe similar for women. For those peopleearnestly seeking to prevent heart disease,the polypill can be combined withthe polymeal.

The polypill and/or the polymeal mayturn out to be part of the answer toincreasing life expectancy, but there area host of hurdles to overcome. The drugcombination and the diet could be usedin conjunction with lifestyle changes,proper medical care, and exercise to helpdelay or prevent the occurrence of age-relateddisease. It is unlikely, however, toexpect that any of these practices willever increase longevity bymodifying the aging process.

Experts in the field ofaging note that men andwomen in the developedworld typically live longernow (75 and 80 years,respectively) than they didthroughout much of history,for a number of reasons—including sanitation, vaccines,and antibiotics. Thisincrease in longevity is due not to alteringthe way people age, but to alteringthe way people live.10

Social Support

There is recent evidence from aprospective study of mortality that givingsupport and comfort to friends, relatives,and neighbors can influence longevity.11Such contributions appear to trigger adesire for self-preservation, and thus volunteeringmay improve both mental andphysical health.

Final Thoughts

Despite advertisements from a numberof nutritional product manufacturersand longevity clinics, currently no diets,vitamin, mineral, or hormone supplements,or behavior or lifestyle choiceshave been demonstrated to slow downthe aging process in humans.3 That possibilitymay lie in long-term geneticresearch and the discovery of age-retardantgenes (3 genes have been identifiedthat appear to promote long life byprotecting against the diseases of oldage) or in the development of stem cellsthat replace dead or dying cells. Researchershave targeted protectivegenes and proteins that slow aging inlaboratory animals and promote longevityin humans. Experimental drugs thatmimic these effects one day may treatthe effects of aging.

In the meantime, the best course ofaction is to follow the advice ofSardinians, Okinawans, and CaliforniaSeventh-day Adventists, who live thelongest.12 Their consensus is (1) do notsmoke; (2) put family first; (3) be activeevery day; (4) keep socially engaged; and(5) eat fruits, vegetables, and wholegrains. It also may be wise to stop thinkingabout or dwelling on your age; recognizeyour mortality; and live each day tothe fullest.

Mr. Sherman is president of ShermanConsulting Services Inc.

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