Longevity Briefs: What’s Special About Red Blood Cells In Long-Lived Humans?

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

The problem:

Lacking in DNA or cellular organs (organelles) and serving mainly as oxygen carriers, red blood cells may seem boring in comparison to their pathogen-hunting white cousins. Yet despite their simplicity, red blood cells still suffer from the effects of ageing. Levels of haemoglobin (the protein that binds oxygen within the cell) decline with age, leading to lower oxygen-carrying capacity. Additionally, with age, haemoglobin may hold on to its oxygen too tightly, contributing to a reduced oxygen delivery to tissues.

Certain aspects of the ageing process appear fundamentally different in those who reach the age of 90 and beyond. Despite outliving the population average by a decade or more, these people often show signs of delayed biological ageing. Studying exactly how the biology of ageing in these individuals differs from that of the general elderly population could teach us something about how to promote healthy ageing and, potentially, how to slow ageing down. To that end, researchers in this study attempt to answer the question: is there anything special about the red blood cells of 90+ year-olds?

The discovery:

Researchers studied the blood of 730 participants from a wide rage of ages – as young as 21 and as old as 102. They started by measuring the P50 of the participants’ haemoglobin – that’s the oxygen pressure at which the haemoglobin is 50% saturated with oxygen. The lower the P50, the harder it is for the haemoglobin to release its oxygen. They found that P50 declined with age as expected but, surprisingly, only up to the age of 89. In the age 90-102 group, P50 was actually significantly higher than in the age 70–89 group and not significantly different from either of the younger age groups.

Next, researchers set out to identify possible molecular explanations for these differences. Since red blood cells have no DNA, they used high-throughput analysis to study and compare the metabolites (molecules needed for or formed in the metabolism) of the red blood cells from 90+ year olds and 70-89 year-olds. Key metabolites that were increased in the red cells of 90+ year-olds primarily included those involved in oxygen release, anti-inflammation, and antioxidant defences. For example, red cells from the oldest individuals had more 2,3-BPG, a byproduct of glucose (sugar) metabolism that sits in the middle of the ‘donut-shaped’ haemoglobin molecule and encourages it to let go of its oxygen.

The implications:

Red blood cells lack mitochondria, the power plants that use oxygen and nutrients to power the cell. As such, despite carrying a lot of oxygen, red blood cells don’t use any of it themselves. This constant presence of large amounts of oxygen leads to some oxidative stress – oxygen reacts to form reactive oxygen species (ROS), highly reactive molecules that damage the cell over time. It seems like the red blood cells of many 90+ year olds have better defences against such damage, as well as differences in glucose metabolism that allow their haemoglobin to continue to release its oxygen effectively.

It’s worth noting that, while comparing the 90-102 year-old group to other age groups, there was still significant variation within the groups. So while the 90-102 group compared favourably to the 70-89 group in many ways, many within the oldest group still had a worse P50 or antioxidant capacity than the majority of people in the group below them. Thus, these characteristics don’t seem to be a requirement to reach the age of 90, they may simply make it more likely. Whether this knowledge can be leveraged to live longer is another matter, but it’s reasonable to suspect that interventions like diet and exercise to reduce inflammation and oxidative stress might favour some of these red blood cell characteristics. That said, there is also likely to be a significant genetic component.