biomarkers

How to determine your biological age

To reflect overall aging, you need to measure a range of factors from many systems, including physical and mental factors that will vary with age. What is termed your “biological age” is the sum of these factors. It compares all your body’s functions with those of your peers. The idea has merit because it should identify those who are “young for their age”, or “old for their age”.

 

Health and aging

Assessment of your biological age includes detection of risk factors and early signs of disease as predictors of premature mortality. However, aging is far more than the absence or presence of disease. Equally, there are many factors that predict lifespan that have nothing to do with the aging process. Nonetheless, practitioners have traditionally looked to signs of disease as the most convenient way to measure biological age. This is mostly because lifespan is determined by the time it takes to die (usually of some disease).

Certainly, disease prevention is a key component of any strategy to slow aging but, while the presence of disease potentially compromises longevity, its absence does not guarantee it. In aiming to stay healthy and increase your healthspan, you need to estimate how well you really are as well as how sick you might be.

Biological age is also not the same thing as health status, though of course the healthier you are, the more likely you are to be biologically younger relative to (unhealthy) others.

 

Measuring the causes

Measurements of some of the mediators or causes of aging are often used to determine your age, as more active aging usually implies an older biological age. For example, measures of oxidative stress, inflammation, glycation, stress and hormone levels are all important determinants of many age-related changes and are consequently used by some practitioners as a means to judge you as older or younger than your chronological age.

These kinds of tests can be handy, as the results can be directly modified by interventions that you can choose, giving a sense that aging is also being modified. While this may very well be true, there’s a number of limitations that make extrapolation of age from a single blood or urine test problematic.

  • For many tests there are no age-standardised reference ranges to know that you are more or less than your peers; to know if your level is high or low for you and impacts on your health today and in the future. Even if there is a normal range, “normal” simply means you are functioning at the same level as your peers and every test has a normal range.
  • Aging is the sum of a number of processes. Consequently, any assessment, as well as any intervention strategy, must reflect and address of range of processes. Single measures of any one thing fail to accurately reflect changes in the whole.

In general, the more comprehensive the choice and assessment of parameters in all the important regulatory systems, the better their ability to predict the cumulative effects of aging and, ultimately, its outcomes.

What to measure?

It is possible to measure elements of body composition, physical performance, mental performance, hormonal levels, nutritional status and biochemical function to compare with age-determined controls. The collection of these elements, which are of course interrelated, anyway, will offer reproducible insight into your aging status.

There is, however, no accepted evidence-based formula or equation at this time to calculate a standardised biological age. What we do have is a group of markers that paint a dynamic view of age-related health. You can use this to assist you in assessing your aging progress and make adjustments to your lifestyle that will encourage as much quality of life as possible.

Health and youth, though not completely interchangeable, do have considerable overlap in the wellbeing sense and are much more than simply the absence of disease. However, as the lessening of life, in both its quality and quantity, is often caused by disease processes, the exclusion and avoidance of such disease plays a major role in slowing aging.

 

Wellness screening

While disease-screening tests are not true biomarkers, the most important of them should be considered in assessing your aging status. The number of blood tests available (not to mention salivary, urinary and hair analysis testing) is extensive to say the least and it’s not in practical to “test for everything”. The standard model of visiting a suitable practitioner who takes a medical history, performs an examination and determines appropriate investigations has yet to be bettered. This holds true in the anti-aging area, too, where it can be adapted to not only find or exclude disease but to quantify, influence and track the rate of aging (or preferably the lack thereof) through relevant markers.

Most good doctors in the anti aging field will ask you to complete a questionnaire. This should cover not only your own medical history and symptomatology (if present), but also that of your family; obviously, genetic influences cannot be over-estimated.

The appropriateness of investigations can be a debatable issue. Sometimes, expensive testing can be part of a practitioner’s revenue and has little or no advantage over a simpler, cheaper test. This can become even more relevant in ongoing monitoring of a medical intervention with numerous tests and mounting expense. Monitoring is certainly necessary, though. There is an old saying: One test is a snapshot, two gives a trend.

Salivary testing for hormonal levels is considered mandatory by some practitioners, a waste of time and money by others. Occasionally, the special-interest area of the doctor dictates the ordering of expensive and exotic investigations of doubtful relevance. An awareness and involvement of you, as a patient, in their investigation and treatment is to the benefit of all concerned.

When testing to establish how to slow the aging process, you need to assess your current state of wellness. How well are you aging (or not)? What is your current disease risk and how are the key systems and organs operating? Another thing to note is there is no purpose in performing any test unless you can then implement targeted strategies to improve your wellbeing and health.

Biological age markers

A biomarker is a measure of a physiological function or effect, which can be aligned to a known age-related range of values to allow ongoing comparison. Following are the tests you can try in conducting a thorough whole-of-body audit.

Blood pressure

Blood pressure levels have a number of characteristics that make them a suitable biomarker of aging. In particular, the systolic blood pressure, which is the highest pressure achieved by the beating heart, generally increases as we get older because of the increasing stiffness of blood vessels (hardening of the arteries).

Cholesterol

Measuring cholesterol levels is an important part of cardiovascular risk assessment AND also appears to be useful component of biological age. Levels of bad cholesterol (contained in low-density lipoprotein (LDL) particles) rise as we get older and, the higher your LDL cholesterol levels, the higher your risk of heart attacks, strokes and other diseases of the blood vessels that shorten life expectancy.

Equally, levels of good cholesterol, contained in high-density lipoprotein (HDL) particles, are used as a marker of the ability of the body to remove bad cholesterol from the walls of blood vessels and put it back into safer storage sites (reverse cholesterol transport). The higher your HDL cholesterol, the higher your capacity to reduce the effects of bad cholesterol, particularly with regards to the development and progression of heart disease, so that individuals with high levels of HDL cholesterol have lower risk of heart disease and strokes and greater longevity.

Blood sugar

The ability to maintain sugar levels in the optimal range is a key requirement for good health and wellbeing. We normally have significant reserve capacity, so even when faced with an enormous meal, our ability to process and store the energy remains highly efficient. However, this reserve is slowly eroded as we get older, ultimately leading to impaired glucose tolerance and the onset of diabetes.

Long before this point, though, it’s possible to measure this reserve capacity and, with it, estimate the loss of function associated with the aging process. One way to test for this is using a glucose tolerance test (GTT), in which a large amount of sugar is either taken orally or injected and its effects on the release of metabolic hormones measured. Elevated levels of insulin denote a resistance to its effects. Individuals with lowest insulin levels appear to have the best health and live longer.

Another way to look at the body’s capacity for sugar regulation is to measure the level of sugar modification on some of its proteins. In the healthy human body, every red cell and the haemoglobin (Hb) protein it contains stays in circulation for about 100 days. During that time, it is exposed to the fluctuations in sugar levels that occur with eating and metabolism. Just as the thickness of the rings on a tree can tell a good year from a bad year, in the same way how much the sugar coats our haemoglobin distinguishes good sugar control from bad.

The better sugar levels are controlled by your metabolism, the less modified the haemoglobin will be over the course of its 100 days. Measuring the level of sugar modification (called the HbA1c) can therefore be one useful way to look at metabolic functions over a long period and across normal activities, rather than relying on a single snapshot. It can also be readily followed to track changes in metabolic function and has been shown to be strongly associated with adverse health outcomes and survival in a range of populations.

Kidney function

The human kidneys do an important job filtering the blood, clearing toxins and maintaining the balance of your inner sea. If this function declines, it leads to a state of increased vulnerability, where even small problems such as a hot day can lead to a bad end. Keeping your kidneys healthy is an important way to slow aging.

In individuals with impaired kidney function, a number of toxins can accumulate (such as advanced glycation end products (AGEs), free radicals and damaged fats). This leads to “accelerated aging” and many of the symptoms and diseases of old age occurring in much younger individuals. Even small changes in kidney function are associated with an increased risk of premature mortality.

Kidney function is conventionally measured in two ways. First, the capacity to filter the blood and clear it of toxins is estimated by measuring the glomerular filtration rate (GFR). This is usually performed by a simple blood test and an automatic calculation based on age, gender and ethnicity.

Another sign of early kidney damage is the loss of large proteins such as albumin into the urine, where they aren’t normally found. Increased excretion of albumin in the urine or a reduced GFR are both associated with reduced survival, with those individuals with the highest levels of albumin excretion (albuminuria) or lowest GFR having the worst prognosis.

Body composition

Body composition is a key determinant of health, disease and disability. Your body changes significantly as you get older and some of these changes can be used to track the process of aging. Testing options include:

  • BMI (body mass index). BMI = weight in kilos divided by height in metres squared. A BMI over 30 means you are obese. Between 25 and 29 = overweight. BMI has its limitations: increased muscle mass, such as in those who exercise regularly, can increase weight and therefore BMI. Equally, muscle loss as you get older can result in a lower BMI and complacency even though the body’s composition may still be highly abnormal.
  • Waist circumference. The deposition of fat around the waist, and particularly around the organs inside, is probably a better marker of compositional changes, so waist circumference is probably the best measure of fatness and therefore the best predictor of its impact on your longevity. In men, waist circumference greater than 94cm and in women greater than 80cm is considered overweight and indicating probable internal fat deposits.
  • Bio-impedance analysis, which can determine percentage of body fat, lean muscle mass, water content and metabolic rate.

Bone density

Decreasing bone density is also a sign of aging, particularly in postmenopausal women, and is typically measured by dual energy X-ray absorptimetry (DEXA) scanning. Bone density is usually measured in the spine, the hip and sometimes the wrist, as these sites are where fractures are most common. Your bone density is compared with that observed when bone density is at its maximum (ie, when you are young). This is the T-score — the higher your T-score, the better your bones are.

Physical performance

Physical performance again tends to deteriorate as we age and investigations that measure such things as stamina, strength and flexibility can also be classed as biomarkers. Tests here cover:

  • Lung function
  • Grip strength
  • VO2 max (endurance exercise potential)
  • Cardiac stress

Mental performance

Cognitive tests are widely used to examine the impact and rate of aging on the brain. Aging is associated with a progressive decline in short-term memory and spatial skills from middle age onwards. This is, however, highly variable from individual to individual, though cognitive tests are very useful as monitoring mechanisms.

The best known of these tests is the quaintly named mini-mental test administered by doctors to assist in the diagnosis and assessment of treatment response in dementia patients. Newer tests include diagnostic EEGs or mind maps.

Hormone levels

Deficiencies, or relative deficiencies, of hormones (at the edge of the bell curve) give established symptom complexes and should be treated. Those doctors who subscribe to the neuro-endocrine theory of aging believe that in part, at least, you age because your hormone levels drop. There can be little doubt that across the board most of your hormone levels do drop as you age. We also in some cases become less sensitive to the hormones we do produce. The hormones DHEA and IGF1 (the primary metabolite of growth hormone) have both been suggested as the most accessible stand-alone biomarkers we have. Statistically, they show a progressive and largely predictable decline with age.

A special case is, of course, the peri-menopausal patient. Few areas in medicine engender such controversy. HRT or not? Bio-identical hormones or not? Troche, creams, patches or capsules? Long term or short term? The pendulum of medical opinion here has swung with embarrassingly great frequency and amplitude over the past few years. The most sensible approach is to remember that you are an individual and, as such, you need to find a doctor who understands your specific objectives, your appetite for risk and change and who will treat you accordingly.

In an anti aging sense, if the decision is to return hormone levels to those of youth, for non-cycling hormone levels (biomarkers) the goal should be figures similar to those of a 25-year-old. Such correction should be done comprehensively, not partially or haphazardly, and be monitored clinically and serologically for results.

 

Useful hormonal biomarkers of aging

  • IGF1 (growth hormone marker)
  • Testosterone/free testosterone
  • DHEAs
  • TSH, T3, T4 (thyroid function)
  • Oestrogen, particularly in menopausal women
  • Progesterone, particularly in menopausal women
  • FSH

Biochemical/organic function

As part of any aging assessment it would be remiss to neglect basic biochemistry. Indeed, as organic function deteriorates as you age, particularly kidneys, such testing can be included under the biomarker banner. Tests here would include:

  • FBC (full blood count) to exclude anaemias, leukaemias and other blood anomalies or reactivities
  • LFTs (liver function tests), a highly sensitive test for liver inflammation or even a minor ethanol indiscretion the previous evening
  • U & Es (urea and electrolytes) to test kidney (renal) function and overall electrolyte balance

 

Disease screening tests

  • Breast cancer: mammogram/ultrasound for women over 40
  • Cervical cancer: PAP smear (twice-yearly from when sexually active)
  • Skin cancer: skin check yearly for all adults
  • Prostate cancer: PSA and prostate examination twice-yearly for men over 40
  • Diabetes: fasting serum glucose regularly (diabetes is a disease heavyweight)
  • Bowel cancer: colonoscopy (over 50s and five-yearly or as genetically indicated)
  • Cardiovascular disease (heart disease and stroke)
  • Lipid profile (cholesterol splits, triglycerides, apolipoproteins and lipoprotein a)
  • Homocysteine (this is an independent cardiovascular risk predictor)
  • CRP (C-reactive protein)
  • Fibrinogen
  • Cardiac stress test as indicated
  • Arterial waveform analysis (pulse tonometry)

Nutritional profile

A blood test to establish your basic nutritional state should also be part of an anti aging assessment. This is particularly true when dealing with vegetarians or vegans or in women with heavy periods. There is a much looser correlation between youth and superior nutrition than there is with other health markers. Basic tests include:

  • Iron studies
  • Serum B12
  • Red cell folate

Trace minerals and other vitamin levels can be tested if indicated, but not usually in a scattergun approach. Such testing could include iodine, vitamin D and zinc levels.

What’s in your genes?

To talk about biomarkers, road maps and health behaviour modification, which is what anti aging medicine largely is, without acknowledging the elephant of genetic testing slowly appearing in your living room would be impossible. In a new, largely unregulated (should it be?) and exciting (though not that exciting yet) development, you can now have your genetic code unlocked even without a medical intermediary. Various combinations of gene testing are being offered commercially and can be a better marker of risks than a simple family history.

Most diseases result from a complex set of both genetic and environmental factors. Genetic test results are based on percentage predictions, telling you your risk for getting one or other condition based on previous associations. Inheritance of certain gene sequence mutations increases or decreases the chance, although it does not guarantee this, that a person will develop a specific problem. Only for a handful of single-gene inherited disorders can it make precise predictions on whether you will develop the disease or not.

Genetic testing will probably become commonplace in the years to come, perhaps gaining entry to the medical marketplace through preventive or anti aging medicine.

 

Anti aging ideals

Here is a classic test result for a man aged 50 who is aging really well

  • BMI of 22
  • Waist measurement of 87cm
  • Ten per cent body fat
  • Positive T-score
  • Blood pressure of 125/70
  • Passes mini-mental test
  • Hormone levels are those of a 25-year-old, particularly his DHEAs and IGF1
  • Total cholesterol is 3.5
  • Homocysteine is 8

None of these is a guarantee of aging well, but they’re a good start!

 

 

 

The WellBeing Team

The WellBeing Team

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