101 Facts About Ageing #47: White Blood Cell Number And Function During Ageing

As Daniel Patrick Moynihan, an American sociologist, politician, and diplomat once said: “Everyone is entitled to his own opinion, but not his own facts”. And we wholeheartedly agree. A shared set of facts is the first step to building a better world with longevity for all. In that spirit, we are creating a series that covers 101 indisputable facts about ageing, health and longevity.

In fact #29, we discussed the role of inflammation during ageing. Inflammation is part of the innate immune system – the arm of the immune system that is able to respond rapidly to any pathogen regardless of whether your body has ‘seen’ it before. The other arm of the immune system is called the adaptive immune system – adaptive, because it is able to hone its response against the specific pathogen it is fighting. The adaptive immune system then preserves information about the pathogen so that the same response can be quickly mounted again should re-infection occur. The adaptive immune system is composed of cells called lymphocytes, so named because they are the main cell type found in the lymphatic fluid. The two types of lymphocyte most people will be familiar with are B cells and T cells. The former produce antibodies against the invading pathogen, while the latter engage in many functions – some kill cells infected by viruses, some boost other immune cells, and some block the activity of misbehaving immune cells. The adaptive immune system is very powerful, and a well functioning immune system depends on a healthy population of lymphocytes.

There are two main changes that occur in the adaptive immune system during ageing. The first is a decline in the number of lymphocytes. The graph below shows the average density in the blood of two types of white blood cell: granulocytes (black circles), which are part of the innate immune system, and lymphocytes (white circles). While granulocytes remain relatively stable, lymphocytes fall sharply within the first two decades of life, then again more gradually after around the age of 40. When it comes to declining lymphocyte numbers, the loss of a particular type of lymphocyte – the naïve T cell – is especially important. These are cells that have never encountered a pathogen before, and have the potential to react to a new, previously unseen invader. The fewer naïve T cells one has, the less effective the immune system will be at responding to new threats.

The other major change is that lymphocytes become harder to activate with increasing age, and when they do activate, many don’t do their jobs as effectively as before. B cells from older individuals don’t produce as many antibodies, for example, while T cells produce weaker immune-boosting signals.

These changes occur for a few reasons. All blood cells are ultimately born in the bone marrow, where hematopoietic stem cells retain the ability to divide and produce any blood cell type. With age, these stem cells become dysfunctional and start to produce fewer lymphocytes in favour of myeloid cells (red blood cells, platelets, granulocytes and monocytes). The thymus (the organ in which T cells undergo ‘quality control’) degenerates with age, resulting in a decreased output of naïve T cells. As for the reduced activity of T cells, this is mainly caused by age related changes within the cells themselves – factors such as telomere shortening and mitochondrial dysfunction. If you want to learn more about these changes, check out the hallmarks of ageing series.