*SAGE editors selected this article by Dr. Chris Wiley as the First Place winner of our 2015 SAGE blog contest. Chris was also one of the winners of the 2014 SAGE contest. Congratulations, Chris!

Most of us tend to think of our age as a number, usually signified by the number of candles we end up blowing out on top of a cake each year.  As we age, however, we tend to notice that all not all of us are aging at the same rate.  This is because aging extends beyond the simple passage of time.  Many people exhibit robust health into their eighties, nineties, and some lucky few remain healthy past the first century of life.  By comparison, many people develop health issues at relatively young ages.  A recent study out of the University of Otago in New Zealand (the “Dunedin Study”) suggests that rates of aging can be measured even in relatively young adults.  Importantly, this study found that indices of rapid aging correlate with future health prognosis.  In other words, if you are aging quickly now, you are more likely to develop the complications of age faster than a person of the same chronological age who is aging more slowly.

But what are these markers of biological aging, and how are they useful?  They are the key variables that, when measured, provide an index of future health.  While our understanding evolves over time, here are some of the most salient markers of aging in use today:

The biomarkers of today – physiological measurements.  Various groups have used a combination of different markers to assess physiological age.  The Dunedin Study, for example, used 18 different markers of health.  These markers included body mass index (BMI), cardiorespiratory fitness, arterial pressure, and gum health – all relatively easily performed at a doctor’s office and available today.  Each of these markers reflect the decline in the body’s ability to perform its normal physical functions over time.

Blood biochemistry tests – measuring aging in a test tube.  Many common assays that result from routine blood work can be used to measure the rate at which a person is aging.  In the Dunedin Study, the authors utilized a combination of lipoprotein(a), high density lipoprotein (HDL), and total cholesterol – combined with triglycerides – to compose a lipid profile of study participants.  They also measured glycated hemoglobin – a marker of diabetes.  They studied hs-CRP (a marker of inflammation), as well as white blood cell counts, both of which increase with age.  Similarly, urea nitrogen and creatinine clearance tests were used to assess kidney health.  Together, these tests can give important information about body homeostasis from a simple blood draw.

DNA alterations – the biomarkers of tomorrow.  Human DNA does not stay the same throughout our lifespans.  As time goes on, our DNA changes in many notable ways:

Telomeres:  Most notable among age-associated changes, telomeres are unique DNA structures at the ends of human chromosomes that act like locks on a zipper, prevent our DNA from unraveling.  With each cell division, our telomeres erode, and eventually they become too short and our cells stop dividing.  Because of this, telomere length can predict biological age.  In the Dunedin study, leukocyte telomere length was used as a biomarker for aging.

Mitochondrial DNA mutations:  More than nuclear DNA, mitochondrial DNA is especially vulnerable due to A) its location in the mitochondrial matrix – a site with high proximity to damaging reactive oxygen species (ROS); and B) the relative paucity of DNA repair mechanisms available in the mitochondrion.  Mitochondrial DNA mutations accumulate over time, and can therefore be predictive of biological age.

Epimutations:  Human DNA is methylated across much of the genome.  This modification is largely repressive, keeping genes from being activated when they aren’t supposed to be.  Human DNA methylation patterns fluctuate with age, becoming lost in some places while other areas gain methylation.   In twin studies, siblings’ epigenomes become more and more different over time.  Changes in methylation of key sites can therefore predict biological age.

Which markers will serve us best as predictors of biological age?  Studies outside of the Dunedin Study, such as the Baltimore Longitudinal Study of Aging (BLSA) use a different combination of biomarkers.  The European Study to Establish Biomarkers of Human Ageing (MARK-AGE) used a combination of techniques to discover and test new biomarkers of aging.  One of the greatest challenges for future clinicians will be to integrate these new DNA biomarkers of aging with those physiological and biochemical markers that are already in use today.