Racemisation of L-Aspartate is a Function of Ageing

L-Aspartate is the predominant enantiomer of Aspartic acid in the human body. Gradually, over time, L-aspartate undergoes racemisation to D-aspartate at body temperature. (Racemisation is the conversion of the optically active isomer to the optically inactive one). This has all round implications.

Consider this problem. Enlargement of the aorta, emphysema, laxity of skin and bladder dysfunction are all age related problems. The factor common to these areas- the aorta, lungs, skin and bladder- is a high proportion of elastin. Elastin is thousand-fold more stretchable than collagen, so it is quite intuitive that it should be present in organs/blood vessels that need to stretch. However, it is also true that a high level of elastin predisposes these tissues to ageing faster than tissues with low elastin content. It turns out that elastin has a far lower turnover than fibrillar matrix proteins such as collagen. This is nicely illustrated by a rising proportion of D-aspartate in elastin in tissues such the aorta with age. The proportion of D-aspartate in collagen remains constant at around 3% in the young and elderly aorta, but the proportion of D-aspartate in elastin rises from 3% to 13% between the two extremes of age, illustrating that senescent elastin fibres are not replaced, while the turnover of collagen remains relatively invariant. Thus, D-aspartate tends to accumulate in the longest lived elastin fibres. The gradual erosion of elastin content with age translates into a dilating aorta, emphysema, etc.

This principle is utilised in determining the age of a deceased person when only remnants of tissue are available. Since teeth often outlast the rest of the body, the D-aspartate content of dentine is used for this purpose, but equally, another tissue such as epiglottis or skin could be used. One simply need compare the D-aspartate content of the whole tissue with the D-aspartate content of the contained elastin fibres. The older the person, the higher will be the proportion of D-aspartate in elastin.

Accuracy of Smartphone Apps To Measure Pulse Oximetry

Some smartphones have a pulse oximeter function. Samsung, for example has an app called Digidoc, which uses the camera and the flash inbuilt into the phone to give a an arterial oxygen saturation. To understand how this works, it is perhaps important to understand how standard pulse oximetry functions, so that we may compare the two approaches.

The standard pulse oximeter is based on the principle that oxygenated haemoglobin (oxyHb) and deoxygenated haemoglobin (deoxyHb) absorb various wavelengths of light differently. Thus, as the graph below illustrates, oxyHb absorbs more infrared light than deoxyHb, while deoxyHb absorbs red light far better than oxyHb. (Pnemonic: SeXy DARLing- At SiX hundred wavelength, Deoxygenated haemoglobin Absorbs Red Light)

The pulse oximeter has a diode for emitting red light (wavelength 660 nm) and one that emits infrared light (wavelength 940 nm) separately. These are passed in turn through the finger inserted into the probe, and a screen below the finger (with its contained artery) measures the amount of light coming through. It also measures the amount of ambient light passing through the finger and subtracts it from the total light traversing the finger.

The oximeter cleverly ignores the "noise" from absorbance contributed by tissues such as skin, muscle etc (because these too absorb light) by only measuring light absorbance when it is pulsatile, i.e. generated by arterial pulsation. It thus ignores the blood flow in veins, which is of course non-pulsatile.

It is thus important to look at the graph (called a plethysmograph) of oxygen saturation generated by the oximeter or app. it should look something like this. If the graph looks like the tracing on the top, you are OK. If it looks like the one at the bottom, don't trust it. The plethysmograph is as important as your oxygen saturation reading. If the graph looks unfamiliar, the reading is not accurate. (Pnemonic used by anaesthetists: SpO2- See pleth before O2)

Thus it is intuitive that depending on the amount of oxygen present in arterial blood, the relative amount of oxyHb versus deoxyHb will vary. With this, will vary the ratio of cumulative red light absorbed versus the cumulative infrared light absorbed. Thus, at 100% arterial oxygen saturation, the only contribution will be from oxyHb, and the red:infrared absorbance ratio will be that of oxyHb. Conversely, at 0% oxygen saturation, the red:infrared absorbance ratio will be that for deoxyHb. At various intermediate saturations, the ratio will be between the 2 extremes, and the computer can easily tell what proportion of Hb is oxygenated from a given figure. This sort of analysis is called "ratio of ratios".

The pulse oximeter readings were standardised by measuring oxygen saturations in healthy volunteers given fixed amounts of oxygen to breath in a previously titrated oxygen/air mixture. However, oxygen saturations below 75% were not used due to reasons of safety and below this level, mathematical methods are used to calculate oxygen saturation.

Now to the Digidoc app used by Samsung. This is based on using white light (from the flash), which is of course a mixture of all visible lights. The camera measures the residual light coming through the finger. Instead of using the ratio of ratios method, the app relies on a "neural network" created from 38 normal volunteers, who were asked to breath room air for 30 minutes and then advised to hold their breath for as long as they could. Reference values were thus obtained for absorbance of white light for all levels of oxygen saturation between 85% and 100%. Saturation of oxygen rarely falls below 85% with breath holding.

It is important to state that the app is not accurate below 85% oxygen saturation due to the above reason. It should therefore not be used for detecting hypoxia, as in subjects with COVID-19. The purpose of the app is to establish baselines for a given person pursuing exercise and sports and compare their oxygen sats before, during and after exercise. Unfortunately, it is widely used by people with lung disease such as COPD, which it is not intended for.

There are 2 separate studies, one in adults and one in children, which compared the Samsung oximetry app to a standard pulse oximeter. The first study also compared the readings to arterial blood gas measurements. Both studies found that the app is reliable and accurate. The app also measures pulse rate accurately. However, using a probe that plugs into the smartphone (available to purchase) increases accuracy slightly.

IMO, this is an useful app for daily exercise and for sportsmen, just like the estimated VO2max on Garmin watches. However, it was never intended for medical usage.

References:
1. https://www.howequipmentworks.com/pulse_oximeter/#:~:text=The%20pulse%20oximeter%20works%20out,of%20infrared%20light%20absorbed%20changes.
2. https://s2.smu.edu/~eclarson/pubs/2018pulseox.pdf
3. https://pubmed.ncbi.nlm.nih.gov/29215972/
4. https://pubmed.ncbi.nlm.nih.gov/30904343/