Aging Biomarkers – Chronological v Biological Age

Chronological age can be defined as the time measured from an individual’s birth to a particular date. Biological age is more complex, since it positions an individual within its own lifespan and probability of survival, meaning that a 67 year old man with a biological age of 60 is more likely to live longer than a 67 year old man with a biological age of 70. These concepts are related and in some cases the values can be equal but they are not the same thing.

Chronological age is simply a number representing the length of someone’s life to a particular point; therefore it is difficult to associate biomarkers to it since any biomarker with any influence in the capacity for survival would immediately be more related to biological age. A strict chronological age biomarker should be a biological feature that changes over an individual lifespan but doesn’t directly affect the probability for survival.

There are several biomarkers currently being used that don’t influence survival greatly and are related to older individuals, these could be easily called “chronological age biomarkers”. Reduction of the coronal pulp cavity (using radiography) is a very common method used in forensic science, however, in adults most signs of aging like wrinkles and silver hair are features that can manifest at different points in someone’s life and won’t be useful to accurately determine someone’s biological age.

When looking for aging biomarkers that will reveal the biological age of an individual, these can be split between functional (macro) and physiological (micro) biomarkers.

Aging Biomarkers Infographic

Biological Biomarkers

After many decades of research, the scientific community now agrees on 9 hallmarks of aging that relate to physiological processes acting at the cellular level. These are: accumulation of genetic errors due to genomic instability, telomere attrition or degradation, epigenetic alterations, damage of the internal mechanism in charge of quality control for protein synthesis, deregulated nutrient sensing, mitochondrial dysfunction, loss of the capacity to grow and change stem cell exhaustion and altered intercellular communication.

All of the physiological biomarkers considered above provide data about the capacity of the organism to sustain operation of its own processes over time and also about its capacity to withstand different forms of stress.

These nine hallmarks of aging are robust candidates to be considered for any system dedicated to the determination of biological age; however, obtaining accurate measurements of any of them requires a lot of specialized equipment and capable staff, since they cannot be evaluated easily. Some of them like stem cell exhaustion or mitochondrial dysfunction can only be measured by taking a biopsy and performing a longitudinal study in vitro under laboratory conditions, something that most laboratories don’t provide as part of their usual services.

Functional Biomarkers

Fortunately, functional biomarkers are easier to measure and are considered equally valid to measure biological age. These cover both cognitive and physical performance and include visual acuity (Snellen chart), auditory acuity (pure tone audiometry), decision reaction time, grip strength (dynamometers), body mass index (height and weight measurement), blood pressure (systolic and diastolic pressure), lung capacity (spirometer) and memory.

Functional age is a specialized form of biological age, is task-oriented, and can provide valuable information in regards to an individual’s capacity to perform a particular task or its vulnerability within a certain set of conditions.

All biomarkers mentioned in this article have shown correlation with the process of aging in the past, however, a system designed to provide an accurate value for someone´s biological age will have to integrate a large number of these variables at the same time and incorporate an elegant method to accumulate, process and interpret data from a considerable amount of sources.

Under 44? Get ready to live forever!

I found some UK statistics from the UK government’s Office for National Statistics recently – they were prepared for the Department of Work and Pensions to determine how much the government needs to put by in pensions. (If you want to skip the statistics and just want to know when you might live forever, feel free to jump to the last paragraph now!) These statistics are particularly interesting as they look at life expectancy when a person is already aged 65 – so they avoid the big impacts on life expectancy “at birth” statistics from the 20th century including better child birth care, antibiotics and the world wars.

Up until the last few years not only has there been a steady increase in life expectancy at 65, but also a steady increase in the rate it is increasing. To make it easier to see, I’ve not plotted the life expectancy but the year-on-year increase in life expectancy when aged 65. That’s the red line on the graph, smoothed out with a 10 year trailing average (of average male & female life expectancy).

Annual Increase in Life Expectancy Age 65

Using a standard linear trend line (in black) you can see a steady increase.  Now what happens when the black line reaches 1.0? At that point people about to retire will start having their life expectancy increase by one year for every year they live*. So when will that be? Continuing the trend line shows indefinite life extension being reached in 2136.

But what about all the talk about exponential growth in medical technology? Oh yes! Don’t think I’d forgotten about that. Look at the green curve – this is a best fit exponential curve for the same data. Even with the recent trail off it still shows exponential growth. So when does this line reach 1.0? Much sooner – using the formula for the trend line Excel chucked back at me, this curve hits jackpot in 2036, a whole century sooner. So if you’re currently under 44 (in 2015) you’ll reach 65 just as life expectancy is increasing as fast as you’re living – welcome to immortality!

*OK in a year’s time you’re now 66 so not quite at the same point on the graph, but a couple of years later life expectancy will be increasing faster that time passes so this seems as good a point as any to say on average people will be living forever.

Data source: Cohort Estimates of Life Expectancy at Age 65

Air pollution – a significant killer

Last year Public Health England (a UK government body) published a report titled “Estimating Local Mortality Burdens associated with Particulate Air Pollution”- basically how many people die from illnesses causes by air pollution, broken down by region. Although individual deaths cannot be attributed to man-made particles in the air it attempts to determine how many deaths each year are caused by air pollution. And they came up with significant numbers.

Air pollution 3x more deaths

Remember, this isn’t just some academic public health issue, the flip side of deaths caused by air pollution is that some deaths can be avoided. The report assumes an average loss of 12 years per attributable death. And 12 years is a long time in the exponentially growing field of medical technology. Avoiding death by air pollution may not save you from aging, but another 12 years of life might keep you around long enough to benefit from new life saving drugs and procedures.

PHE found that the fraction of mortality attributable to long -term exposure to PM2.5 air pollution (that is, caused by man-made particles smaller than 2.5um) ranges from under 3% to over 8% – so living in a polluted city is three times as dangerous as living in the countryside.

Two plausible ways to reduce the harmful effects of air pollution would be to reduce air pollution or to reduce exposure. You can help reduce air pollution across the country by campaigning for cleaner air (for example join http://healthyair.org.uk/) or finding a local group – there are surprising pollution hot spots even in quite rural areas. Then to reduce your own exposure (because option 1 is going to take some time to happen) consider masks, filtering air in your own home or even moving somewhere with lower pollution. Since reading this report I’ve already started job hunting outside of London to minimise the time I spend breathing killer air.

Here’s a small section of towns and cities through-out the UK – to see your own location the full table starts on page 10 of report – https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/332854/PHE_CRCE_010.pdf

Town or City Particle Concentration Attributable deaths Fraction of all deaths
London, including 12.7 3389 7.2 %
– Westminster 14.9 88 8.3 %
– Bromley 11.1 161 6.3 %
Newcastle upon Tyne 8.6 124 4.9 %
Northumberland 6.9 128 3.9 %
Manchester 10.4 219 5.9 %
Carlisle 6.7 43 3.8 %
Leeds 9.7 350 5.5%
Nottingham 11.4 150 6.4 %
Derbyshire Dales 8.2 33 4.7 %
Birmingham 11.4 520 6.4 %
Worcester 9.5 43 5.4 %
Cambridge 10.2 47 5.8 %
Ipswich 10.0 63 5.6 %
Reading 10.5 62 5.9 %
Southampton 11.1 110 6.2 %
Oxford 10.6 55 6.0 %
Bristol 10.2 196 5.8 %
Cornwall 6.7 221 3.8 %
Cardiff 9.5 143 5.4 %
Isle of Anglesey 5.5 26 3.2 %
Glasgow 8.3 306 4.7%
Aberdeenshire 5.6 70 3.2 %
Belfast 9.2 141 5.2%