Chronological Age verses Biological Age

There is no escaping the conclusion that age is the greatest risk factor for disease and death.  However, it is also apparent that age, i.e. chronological age (time from birth), is a poor indicator of the actual state of the aging process in our body.  In other words, chronological age does not accurately represent biological age. 

Chronological age, at best, provides an association with a population average of age-related changes.  This lack of individual sensitivity has bothered scientists from the early beginnings of research on aging (some 80 years ago).  Since chronological age fails to precisely define the extent of aging of an individual, there is a need for something better.  This something better is called a biomarker.  It is predicted that a validated biomarker or composite of biomarkers will replace chronological age in health reports in the future. Furthermore, insurance companies will rely on them to better evaluate appropriate therapy for the elderly. 

What Exactly is a Biomarker of Aging

Since chronological age can give only a very rough estimate of the aging process, scientists are seeking a measurement(s) that represents the summation of the age changes in an individual at a particular date.  This is termed a biomarker of aging.   A biomarker will indicate the extent of aging of all organ systems for each individual, and also define the risk of disease for that individual. 

Although finding the ideal biomarkers of aging is an incredibly challenging scientific endeavor, biomarkers of disease already exist and are routinely relied on to direct next steps in treatment.  A familiar example is the PSA (prostate-specific antigen), a substance (biomarker) produced by prostate tumors.  PSA levels give a measure of both tumor presence and efficacy of therapy.  Another example of a disease-related biomarker, albeit less well known, is ANP, atrial natriuretic peptide, levels of which increase in heart failure and subside as heart failure is managed.  Both of these biomarkers provided diagnostic and prognostic information that guides effective therapy.

Candidate Biomarkers of Aging

Biomarkers of aging are varied and range from measurements of physical fitness to molecular DNA changes.  Although there are hundreds of biomarkers of aging that are under serious evaluation, none has taken first place in acceptance by the scientific community.  Two measurements that could be useful candidates are 1) maximal aerobic capacity termed VO₂max and 2) inflammatory mediators.  Both measurements have been used extensively to elucidate age changes in man.

a) Maximal aerobic capacity

VO₂max requires the individual to exercise strenuously (treadmill or stationary bike) for a specified time period during which maximal effort, heart rate, blood pressure, and oxygen consumption are measured.  VO₂max directly assesses the function of the heart, lungs, chest muscles, blood vessels and oxygen carrying capacity of the red blood cells.  Because it is a comprehensive test that accurately measures performance in critical organ systems, it has been used in clinical trials to measure biological age changes independent of chronological age.  Furthermore, test results from this measurement are predictive of future disease.

b) Inflammatory mediators

Scientists have identified many inflammatory mediators that could be valuable biomarkers of aging.  The most recognizable one, C-reactive protein, is now part of many blood sample tests.  Inflammatory mediators such as C-reactive protein are substances released with injury e.g. an open cut or wound, muscle pulls and strains, or blunt trauma.  Everyone is familiar with injury-related inflammation – the pain, redness, and swelling.  As uncomfortable as inflammation is, an adequate healing process requires this initial acute inflammatory state but importantly, only for a brief period.  In contrast, persistent inflammation following an injury leads to permanent, sometimes irreversible, tissue damage. 

During aging, some cells called senescent cells, change their looks and functions and randomly produce unwanted inflammatory mediators in the absence of an injury.  Senescent cells, unfortunately, support a state of chronic low grade inflammation termed inflammaging.  Consequently, inflammatory mediators would be important biomarkers of aging and are currently under intense investigation.

Why the Aging Process Needs Biomarkers

The aging process exerts widespread effects on the body.  It alters the structure and function of all components of our body, from molecules to organ systems.  Furthermore, these changes occur at different rates depending both on genes, the environment (mainly lifestyle choices) and their interaction (see Insight 1). The occurrence of age changes at different biological levels and at different rates produces an incredible heterogeneity (diversity) of aging among individuals.

Although the aging process is an unavoidable deteriorative process, an abundance of clinical data indicate that the appropriate selection of proven anti-aging programs lengthens the time in good health (expands the health span) and reduces the time spent in debilitation and disease (shortens the senescent span).  This is where biomarkers come in. 

The advantage of biomarkers lies in their ability to precisely determine the extent of biological aging at any one time.  This information is important for two reasons:

a)  it permits the individual to engage in the most relevant anti-aging program to retard aging and

b)  it provides individual  assessment of risk of future disease and disability, allowing an opportunity to reduce the risk.

Conclusions

The observation that chronological age fails to define biological aging, stimulates the continuing search for biomarkers of aging.  It is predicted that in the future biomarkers of aging will replace chronological age, precisely because biomarkers will accurately measure biological age changes in each individual, and additionally predict morbidity and mortality.  Furthermore, since the aging process is modifiable, accurate knowledge of the state of one’s aging provides the opportunity to engage in appropriate anti-aging programs that will promote longevity by extending the years of health.