A while back, I visited David (not his real name), an elementary school classmate of mine. We were very close friends at school, and, obviously, of the same age. But when I saw him again, after many years, I was taken aback. He looked old and he behaved old, though, to tell the truth, he was never as exuberant and rambunctious as the rest of us.

His wife brought out our class graduation picture and I was shocked again. About a third of the class had lost their lives in the wars of Israel! But just as shocking was the number who already died of heart disease, cancer, dementia, and other diseases. When we were children, we were full of life, naive, and optimistic. None of us thought about getting sick or dying sometime in the not-so-distant future. But, sadly, some of us did.

I wonder now, how could anybody predict that one of the brightest kids in the class would end up with Alzheimer’s dementia? Or that another, a national record holder in his age group in the 100-meter sprint, would die of a heart attack?

Who could have divined which of my classmates would remain youthful, physically fit, and sharp minded as the years flew by?

How can anybody tell who is going to age rapidly or die relatively young and who will be healthy and fit in their chronologically older years? The answer has been, nobody can…until now.

 

Predicting the speed of aging

A recent paper by Daniel Belsky and his colleagues from Duke University, King’s College in London, Hebrew University in Jerusalem, UCLA, and Otago University in Dunedin, titled, “Quantification of biological aging in young adults,” offers hope that science is finally taking a crack at predicting the speed of aging.

The researchers analyzed data from the Dunedin Study, a landmark longitudinal study that has tracked more than a thousand people born between 1972-73 in the same town, Dunedin, New Zealand, from birth to the present.

As part of their regular reassessment of the study population, they interviewed and performed other assessments on participants. In addition, they measured a variety of physiological functions that are part of a regular physical checkup, like blood pressure, liver and kidney function, and HDL cholesterol. They measured lung function, cardiorespiratory fitness, and the immune system as well as the condition of the retinal arterioles and venules (these tiny vessels reflect the status of the brain’s blood vessels). They also assessed dental health as well because several species of bacteria associated with periodontitis (erosion of tissue and bone that support the teeth) have been found in the atherosclerotic plaque in arteries in the heart and elsewhere. This plaque can lead to heart attack.

 

Measuring the length of telomeres

Telomeres. Photo credit: Flicker (CC BY-SA 2.0)
Photo credit: Flicker ((CC BY-SA 2.0)

The researchers also followed an unusual measure, the length of chromosomal telomeres. Telomeres are stretches of DNA at the ends of each chromosome. They have been compared with the plastic tips on shoelaces because they keep chromosome ends from fraying and sticking to each other, which would destroy or scramble an organism’s genetic information.

Sounds great, but here is the rub: Each time a cell divides, the telomeres get shorter. When they get too short, the cell can no longer divide; it becomes inactive or “senescent” or it dies. The shortening of telomeres is associated with aging, cancer, and a higher risk of death.

 

Plotting the aging process

In all, the study looked at 18 markers. The researchers then went back into the archival data for each subject and looked at the measurement of these 18 biomarkers at age 26, 32, and 38. From this, they drew a slope for each variable.

By mathematically combining all the markers into one line (called a regression line), they determined the “Pace of Aging” for each individual. For example, a 38-year-old with a biologic age of 40 is calculated to be aging at a rate of 1.2 years per year over the 12 years the study examined.

Most participants clustered around an aging rate of one “biological” year per chronological year. By definition, that’s what is expected; most people age at a normal rate—that is how we define “normal”. But others were found to be aging as fast as three years per chronological year. Many were aging at zero years per year, in effect, staying younger than their age.

 

Does the math reflect biological reality?

Is there objective evidence that the 38-year-olds with older biological ages actually perform as if they were chronologically older? Turns out, there is. Study members who appeared to be more advanced in biological aging also scored worse on tests typically given to people over 60, including tests of balance and coordination and solving unfamiliar problems. The biologically older individuals also reported having more difficulties with physical functioning than their peers, such as walking up stairs.

What’s more, the researchers asked Duke University undergraduate students to assess facial photos of the study participants taken at age 38 and rate how young or old they appeared. Again, the participants who were biologically older also appeared older to the college students. And vice versa, the biologically younger also looked younger.

 

A work in progress

The study is really a work in progress. We don’t know yet if all of the possible aging-relevant influencers were included. For instance, there were no measures of maternal-fetal influences, like nutrition, pre-term birth, birth weight, and so forth. Do they affect the pace of aging? We don’t know yet. Also, in constructing the regression line of the “Pace of Aging,” every variable was given equal weight. Obviously, this is not the case in reality. It is likely that some variables will be more important than others. Further studies will be needed to determine the appropriate weight for each.

 

What about genetics?

One of the obvious questions is: What about genetics? Important, but less than you’d suspect. Twin studies have found that genes account for about 25% of the pace of aging. Put another way, 75% of aging is environmental, basically meaning lifestyle.

I wanted to see it for myself, literally. So, I checked my longevity profile on 23andMe, a saliva-based genomics company. One study showed that I should have been dead by now, 2 studies showed that I am due to die anytime soon, and one study reassured me that I should live to a ripe old age. I am in fact 80 years old, very much alive and kicking. This is not to denigrate the role of genetics in longevity—only to show its limitations.

Having said that, as further research sharpens the understanding of each of the biological marker’s contribution to the pace of aging, as some are deleted and some are added, we will finally be able to project the influence of these variables on the pace of aging.

 

The benefits of predicting the speed of aging

Think of the benefits:

  • We’ll be able to tell in early adulthood if intrauterine growth restriction, like the mother’s malnutrition, predisposes to faster aging
  • Or whether the effects of early-life adversity, like child maltreatment, accelerate aging in the decades before chronic diseases develop
  • Or whether social inequality in health, such as children born into poor households, age more rapidly than their age-peers born into rich ones and can such accelerated aging be slowed by childhood interventions?

Early identification of accelerated aging before chronic disease becomes established may offer opportunities for prevention.

Last but not least, think of the poor souls who try to increase their longevity with severe calorie-restriction diets. As things stand now, we have to wait until they die to know if their efforts paid off. If we could predict the speed of aging by measuring some key biologic markers, we could spare them the agony of lifelong starvation!

Four generations of the author's (on L) family. (Photo © Dov Michaeli
Four generations of the author’s (on L) family. (Photo ©Dov Michaeli 2004)
Dov Michaeli, MD, PhD

Dov Michaeli, MD, PhD loves to write about the brain and human behavior as well as translate complicated basic science concepts into entertainment for the rest of us. He was a professor at the University of California San Francisco before leaving to enter the world of biotech. He served as the Chief Medical Officer of biotech companies, including Aphton Corporation. He also founded and served as the CEO of Madah Medica, an early stage biotech company developing products to improve post-surgical pain control. He is now retired and enjoys working out, following the stock market, travelling the world, and, of course, writing for TDWI.

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