Autoimmune conditions might age us faster

Autoimmunity causes inflammation & inflammation causes premature aging

by Dr. Vedrana Högqvist Tabor

Our aging has been attributed to many genetic and environmental factors. Environmental factors such as diet, stress and pollution, but also genetic factors all have one feature in common: the inflammatory response. The tight balance between the pro-inflammation and anti-inflammation molecules and networks in our body will determine how fast we age. The older we are this delicate balance will tip towards the pro-inflammation.

I am nine years older than my sister, and got self diagnosed with Hashimoto’s a few years ago. My sister got diagnosed with Hashimoto’s earlier this week. She did not have any major symptoms, but has slowly stared to feel different. She did have problems with her digestion, and felt the best when fasting. For her, as for many of us, the diet we follow (or randomly accept) was the major determinant of how we feel.

For my family the pattern of autoimmune thyroid disorder is pretty obvious: our condition worsened as we got older. We all got diagnosed at 30 or older.

Why do thyroid conditions get more frequently diagnosed in the older people?

Is it because we pay more attention to the symptoms as we grow older? Do the symptoms get worse over time?

I always had at least some of the symptoms, but they were trivialised or not talked about at all. Telling my family and friends about my digestive experiences was not a part of my usual conversation repertoire.

As we grow older, we read more and realise there are people with shared experiences, and that the shared symptom experiences have a medical tag to it. Also, the thyroid function check is a part of a semi-standard panel of tests that doctor does when one is over 30 (at least in Germany and Sweden).

At the age of 30 I got diagnosed with a condition that was gnawing on my body for my entire lifetime. It made me wonder what has been going on in my body until then, and how to put the brakes on it now that I am aware of it?

It turned out to be a complicated task. We are not dealing with a simple disease, most of our body is out of its natural and healthy balance for a very long time. We are dealing with the inflammation that causes us age faster, and making us more prone to a spectrum of other diseases.

What does inflammation have to do with the process of aging?

Our immune system is our shield, it protects us from a multitude of diseases. It has perfected itself during the evolution to maximise our survival (and reproduction → read more interesting stuff here).

However, after the childbearing age it seems that our immune system starts to become less reliable and efficient (because, evolutionary speaking, we have served our purpose, so it needn’t protect us no more). That is the time when we become more prone to contract diseases as well as experience increased inflammation (and many of the diseases connected to it, such as heart diseases or Alzheimer’s).

On a molecular level: the perfect communication between all cells of the immune system starts failing, immune cells become slower to react when bacteria or viruses start attacking us. This process has a name, it is called immunosenescence and it is caused by our genes as well as the environment we live in. It means aging of the immune system.

At the same time, as we age, the inflammation rates go up. This phenomenon is called inflammaging. Inflammaging is a result of a number and duration of infections or irritations we experience throughout our lifetime. Importantly,inflammation caused by autoimmune disease has a tremendously strong contribution to inflammaging.

Molecular damage caused by such a continuous inflammation is mostly not apparent at the very beginning of our life, it rather accumulates over many decades, and becomes apparent later in life, when a significant damage is done. That might be the reason we do not detect diseases early on.

On a hormonal level: our immune system communicates with our hormonal system (endocrine system). To give you a feel: hormone cortisol, one of the key stress responders as well as blocker of our immune response, is preventing inflammaging. Another hormone, a precursor of testosterone and estrogen, DHEA (dehydroepiandrosterone) opposes cortisol activity. Our body is trying to fight inflammaging, as cortisol concentration increase as we age and DHEA(s) concentration decrease [1]. The balance between the two hormones is important for us to be able to fight bacteria and viruses, and at the same time prevent continuous inflammation damaging our tissues and causing us age faster.

Stress causes inflammaging

The aging process is induced by different types of stress leading to damage in our cells and their components: DNA, proteins and membranes; through that contributing to the breakdown of our physiological functions [2]. However, while changing our genes would take more than one generation, changes we experience with our immune system are more dynamic allowing fast adaptations to ever changing environment, they are done through epigenetics [18]. Modifications in our immunity are experienced thanks to epigenetically-induced changes. Epigenetic changes allow momentary control of gene activity in any cell without going through trouble of changing (mutating) our DNA, making it easy for changes to happen quite fast and in almost any cell.

The role of epigenetics

As a response to different environmental conditions (diet, stress, chemical exposure or similar) epigenetic changes will be triggered. Those changes do not modify or mutate our genes, they rather switch them on or off, and by that increase or decrease production of different proteins within our cells. There is a scientific proof for epigenetic changes being directly responsible for development and progression of diseases such as autoimmune thyroid disease, rheumatoid arthritis, diabetes type 2, cardiovascular diseases and cancer [3–7, 8–10].

(Epi)genetics of thyroid disorder

There are at least seven genes shown to contribute to the development of autoimmune thyroid disease, with each of the genes alone having a weak effect, but all of them put together produce stronger effect and cause the disease [3].

On epigenetic level, interferon alpha (IFNa), produced during viral infections (such as flu or common cold) triggers autoimmune thyroid disease through causing epigenetic changes [3,11].

Epigenetic control of our hormones and hormones of our mothers and their mothers

Theories and evidence go as far as to claim some of our ailments (such as autoimmune diseases) are epigenetically determined when we were fetuses or even when our biological ancestors were fetuses [13–17].

Our lifestyle has a direct impact to more than one generation of our biological offspring.

Directing epigenetics and inflammaging with food

Chemical compounds found in nature, such as curcumin (found in turmeric), resveratrol (natural phenol produced by plants in response to injury or attack by bacteria), genistein (inhibitor of blood vessel formation), withaferin Aprotect our heart, neural system and fighting viruses and bacteria [18][19]. They do it through [19]:

1. anti-oxidant activity,

2. lowering down cellular stress signalling,

3. blocking molecules that promote inflammation,

4. blocking molecules promoting metabolic disease,

5. activating genes responsible for metabolism and

6. activating molecules that block inflammation.

Food you eat is more than a mere energy provider. It can indeed shape your cellular health, and through that your overall health [20].

Mild inflammation ages us

Inflammation that we are not aware of, because it is too mild (or low-grade) seems to be the main culprit of our aging. Mostly because we do not recognise it and treat it in time. Research has shown that systemic low-grade inflammation and disturbance in metabolic equilibrium are connected to aging. Once the inflammation is present, in any organ, ageing of our entire body speeds up [21].

Summing it up

The visible set of our health characteristics is the result of the interaction of our genes with both our present environment and the environment of our ancestors. This interaction causes epigenetic changes.

Changes in epigenetic mechanisms modify our immune system function and contribute to faster and unhealthier ageing.

Immunity and inflammation is tightly connected: autoimmune disorders are supported by inflammation and in turn they increase the inflammation locking us into a vicious circle.

What you eat is who you are, but also who your biological grandchildren will be.

In order to prevent or even reverse epigenetic changes that lead to inflammaging, lifestyle dietary adjustments have to be made. That is the next challenge: determine which of the epigenetic changes are reversible, and what diet as well as other lifestyle adjustments are the best way to succeed in reversing epigenetic mark.

My take: as with most of the other health related issues, some of needed adjustments will be very individual (and harder to establish), while the other adjustments will yield success in the general population.

References

1. Baylis D, et al. Understanding how we age: insights into inflammaging, 2013

2. De la Fuente M, et al. An update of the oxidation-inflammation theory of aging: the involvement of the immune system in oxi-inflamm-aging, 2009

3. Hasham A, et al. Genetic and epigenetic mechanisms in thyroid autoimmunity, 2012

4. Miller RL, et al. Environmental epigenetics and asthma: current concepts and call for studies, 2008

5. Villeneuve LM, et al. The role of epigenetics in the pathology of diabetic complications, 2010

6 Schwartz, D. A. Epigenetics and environmental lung disease. Proc Am Thorac Soc 7, 123–125, doi:10.1513/pats.200908–084RM (2010).

7 Gluckman, P. D., Hanson, M. A., Cooper, C. & Thornburg, K. L. Effect of in utero and early-life conditions on adult health and disease. N Engl J Med 359, 61–73, doi:10.1056/NEJMra0708473 (2008).

8. Esteller M. Epigenetics in cancer, 2008

9. Paul DS, et al. Advances in epigenome-wide association studies for common diseases, 2014

10. Mill J, et al. From promises to practical strategies in epigenetic epidemiology, 2013

11. Youngblood B, et al. The early expressed HIV-1 genes regulate DNMT1 expression, 2008

12. Milagro FI, et al.. Dietary factors, epigenetic modifications and obesity outcomes: progresses and perspectives, 2013

13. Teh, A. L. et al. The effect of genotype and in utero environment on interindividual variation in neonate DNA methylomes, 2014

14. Susiarjo M, et al. Epigenetics. You are what you eat, but what about your DNA? 2014

15. Radford EJ, et al. In utero effects. In utero undernourishment perturbs the adult sperm methylome and intergenerational metabolism, 2014

16. Sargent, J. Reproductive endocrinology: you are what your grandmother ate-inherited effects of in utero undernourishment, 2014

17. Topol, E. J. Individualized medicine from prewomb to tomb, 2014

18. Szarc tel Szic K, et al. From inflammaging to healthy aging by dietary lifestyle choices: is epigenetics the key to personalized nutrition? 2015

19. Joven, J. et al. Multifunctional targets of dietary polyphenols in disease: a case for the chemokine network and energy metabolism, 2013

20. Szarc tel Szic K, et al. Nature or nurture: let food be your epigenetic medicine in chronic inflammatory disorders, 2010

21. Jurk, D. et al. Chronic inflammation induces telomere dysfunction and accelerates ageing in mic, 2014

Vedrana Högqvist Tabor