Lupus and Aging: Immunosenescence

Are you over 60 and living with lupus? Even it you are not over 60 yet, it is critical to know how aging affects those of us living with lupus. Read on and find out the facts about lupus, aging and immunosenescence.


Introduction

Life expectancy in most modern, Western societies has increased significantly. Since the 19th century alone, average life expectancy has doubled from roughly 40-50 years of age to almost 80. This longevity may bring wisdom and self-awareness, but it also comes with greater vulnerability to illness and injury. As hard as we may try to stop this, we cannot turn back the clock. Our bodies eventually experience these changes at the cellular – even molecular level. The technical term for the process of aging on a person’s immune response is immunosenescence.

Individuals with lupus may be particularly vulnerable to some of the effects of aging. Some scientists have even theorized that lupus may actually be the result of a premature aging process happening at the microscopic level.  Keep reading to find out how immunosenescence may impact individuals with of lupus or those who may be at risk for developing SLE later in life.


Lupus, Aging and Immunosenescence

Individuals with lupus and those who are elderly do share some key features of autoimmune disease and immunosenescence, such as chronic inflammation, immune system dysfunction and increased susceptibility to infection and disease. These affect not only those with lupus as they grow older, but may contribute to what is called late-onset SLE.

Immunosenescence is a pretty complex process, but some of its most relevant hallmarks include:

  • A weakened acquired immune response to new antigens: As we get older, our exposure to new antigens diminishes, as well as the production of T cells – a class of white cells that fight infections in a number of ways. By age 50, T cell production is <10% of what it was when we were younger. As we age and are exposed to new antigens, it becomes harder and harder for us to fight them.
  • An accumulation of weaker memory T cells: Memory T cells are the cells that survive after a body has been exposed to an antigen or pathogen for the first time and provide protection from future infections. The memory T cells that an individual accumulates when they are younger usually function well, but the memory T cells that an individual accumulates later in life do not protect as well against novel pathogens and antigens, such as COVID-19 virus.
  • Low-grade, persistent inflammation (“inflamm-aging”): Inflamm-aging is the chronic, low-grade inflammation that occurs with age when there is an increase in the production of pro-inflammatory cytokines and C-reactive protein in the body. Chronic inflammation, as individuals with lupus know all too well, can weaken and destroy tissue.

Pre-Existing SLE and Immunosenescence

As an individual with lupus ages, the severity of symptoms and occurrence of flares may actually decrease! Whether due to hormonal changes or to the natural decrease in immunity in general, sometimes the autoimmune response is reduced in intensity.    Yet, older individuals who had lupus when they were young do become more at risk for developing other health-related conditions than the general population. This may be due to a natural increase in generalized chronic inflammation, or to the accumulative effects of years of drug therapy.

As an individual with lupus ages, healthcare practitioners may take a more reserved approach towards drug therapy in order to moderate their effects on aging.  For example, individuals who have lupus nephritis may be prescribed less cyclophosphamides, and other immunosuppressive therapies.

Aging and SLE is still somewhat uncharted territory, however, and there are currently no general guidelines for practitioners to follow. As the percentage of elderly in the general population increases, more targeted research will be needed in order to determine more applicable courses of treatment for those who are aging with lupus.

Late-onset SLE and Immunosenescence

Late-onset SLE is defined as those diagnosed after age 50.  These individuals usually have the same symptoms of others with lupus, though they are typically not as severe. However, the accumulative health risks that come with SLE in general are the same as those who have had it all of their lives. These individuals experience complications associated with chronic inflammation, the generation of autoantibodies and increased vulnerability to illness.

Some drug treatments also pose risks for older individuals, such as:

  • Antimalarials, like hydroxycholoquine (Plaquenil);
  • Corticosteroids and immunosuppressive drugs. These require moderation and constant monitoring;
  • Avoid non-steroidal anti-inflammatory drugs (NSAIDs) whenever possible; and
  • Treatment your other health conditions in order to improve overall health.

While individuals who experience late-onset SLE do not typically experience cutaneous lupus or lupus nephritis, they often experience overlapping Sjogren’s syndrome, arthritis and serositis. They are also at greater risk for developing Raynaud’s phenomenon, cardiovascular damage, hypertension, osteoporosis and cancer.

The demographic for developing late-onset SLE is a bit different than those who develop SLE when they are younger. While women make up around 90% of all individuals who have lupus, the ratio of men to women seems to shift for those who develop lupus over the age of 50 from 1 in 10 to approximately 2.4 in 9.

Apoptosis – the normal death of cells – occurs efficiently in healthy, younger individuals. However, in individuals who are aging and/or have SLE, the normal clearing of the dead (apoptotic) cells may be impaired. Clearing is necessary for regulating inflammation and self-tolerance – the ability to know the difference between self-produced, non-threatening antigens and invaders who have no business in the body. Elderly individuals who did not have lupus when they were younger may get it later in life because of abnormal apoptosis and diminishing self-tolerance.

 


Staying Healthy While Aging with Lupus

Emerging Therapies

While there obviously is no cure for aging, scientists currently researching the following as potential diet therapies to combat the effects of aging and inflammation:

  • Diet: Avoiding foods that may induce inflammation and incorporating foods from the Mediterranean diet may downregulate biomarkers of inflammation such as C-reactive protein and other cytokines.
  • Vitamins and supplements: Including vitamins C and E and zinc may increase T cell production.
  • Probiotics, prebiotics and symbiotics: While the jury is still out on their efficacy, some research suggests that the role these supplements play in the gut microbiome may reduce inflammation for some.
  • Nutraceuticals: Bioactive food components found in fatty fish and some fruits and vegetables may increase T cell and natural killer cell production and reduce pro-inflammatory cytokine production.

Always discuss questions and concerns with a healthcare practitioner before making dietary changes.

Clinical approaches that are currently under investigation include:

  • Growth factors: Growth factor interleukin-7 (IL-7) – a cytokine –  may stimulate mature T cell production and counteract the first signs of immunosenescence.
  • Checkpoint inhibitors: These inhibitors – MoAbs – may block immune inhibitory responses such as the proteins made by T cells, some cancer cells and antibodies.
  • MAPK Pathway: Regulating these pathways that are part of both the innate and adaptive immune systems may decrease the production of pro-inflammatory cytokines.

Staying Healthy While Aging

There are steps that an individual can take to stay as healthy as possible throughout the aging process, especially if an individual has lupus:

  • Keep medical appointments and take drugs as prescribed.
  • Get monitored regularly for osteoporosis.
  • Carefully assess the need for hormone replacement therapy (HRT) with a practitioner.
  • Eat a healthy diet and maintain a healthy weight.
  • Exercise.
  • Quit smoking and drink alcohol in moderation.
  • Rest and get quality sleep.
  • Nurture emotional well-being.


In Conclusion

Immunosenescence affects us all at some point and for those who have lupus, it may explain why it increases the vulnerability to other diseases, making routine healthcare and taking self-care measures imperative to enjoying a long, happy and healthy life. It is important to also check in with practitioners to find out how healthcare protocols change as an individual reaches milestone birthdays – what may not have been necessary at 20, may be so at 60. For individuals with lupus, this may take a little more diligence and maintenance, but achieving optimal health and wellbeing is worth the extra effort!

 

References

Aiello, A., Farzaneh, F., Candore, G., Caruso, C., Davinelli, S., Gambino, C., Ligotti, M., Zareian, N., & Accardi, G. (2019). Immunosenescence and its hallmarks: How to oppose aging strategically? A review of potential options for therapeutic intervention. Frontiers in Immunology, 10(2247). doi: 10.3389/fimmu.2019.02247. Retrieved September 9, 2020 from https://www.frontiersin.org/articles/10.3389/fimmu.2019.02247/full

Effros, R. (2005). Roy Walford and the immunologic theory of aging. Immunity & Aging, 2(7). doi: 10.1186/1742-4933-2-7. Retrieved September 9, 2020 from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1131916/

Franceschi, C. & Campisi, J. (2014). Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. The Journals of Gerontology, 69(1), S4-S9. doi: 10.1093/Gerona/glu057. Retrieved September 9, 2020 from https://academic.oup.com/biomedgerontology/article/69/Suppl_1/S4/587037

Montoya-Ortiz, G. (2013). Immunosenescence, aging, and systemic lupus erythematosus. Autoimmune Diseases, Article ID 267078. Doi: 10.1155/2013/267078. Retrieved September 9, 2020 from https://www.hindawi.com/journals/ad/2013/267078/

Ugarte-Gil, M. & Alarcon, G. (2013). Is there an effective treatment for late-onset systemic lupus erythematosus [abstract]? Future Aging Health, 9(4). doi: 10.2217/ahe.13.26. Retrieved September 9, 2020 from https://www.futuremedicine.com/doi/pdf/10.2217/ahe.13.36

United Nations Economic and Social Affairs. (2017). World Population Ageing. https://www.un.org/en/development/desa/population/publications/pdf/ageing/WPA2017_Highlights.pdf

Van den hoogn, L., Sims, G., Gijsbert van Roon, J., & Fritsch-Stork, R. (2015). Current Aging Science, 8(2). Doi: 10.2174/1874609808666150727111904. Retrieved September 9, 2020 fom https://www.researchgate.net/profile/Joel_Roon/publication/280537942_Aging_and_Systemic_Lupus_Erythematosus_-_Immunosenescence_and_Beyond/links/56791eaa08ae125516efedf6/Aging-and-Systemic-Lupus-Erythematosus-Immunosenescence-and-Beyond.pdf

 

Author: Liz Heintz

Liz Heintz is a medical research writer who received her BA in Communications, Advocacy, and Relational Communications from Marylhurst University in Lake Oswego, Oregon. She most recently worked for several years in the healthcare industry. A native of San Francisco, California, Liz now calls the beautiful Pacific Northwest home.

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