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The Immune System Makes It Harder to Lose Weight as We Age

Many of us have experienced the uphill struggle to control our weight as we get older. We cannot eat whatever we like and stay slim like when we were younger, our holiday indulgences refusing to go away. The battle of the bulge gets harder the older we get, and there was little we could do about it, but now science has come to the rescue and is starting to unravel the mystery of why we find it harder to lose weight as we get older.

A new study led by Professor Vishwa Deep Dixit at Yale University shows how both the nervous system and the immune system talk to each other and, in doing so, control metabolism and inflammation in the body [1]. This study sheds light on why older adults often find it difficult to burn stored belly fat, increasing the risk of a number of metabolic disorders.

Perhaps more intriguingly, the study also shows some potential approaches to targeting the problem, thus helping older adults to improve their metabolism, improve weight control and reduce the risk of metabolic disorders.

Stored fat becomes locked in limbo

Regardless of their weight, older adults all have an increased ratio of belly fat compared to younger people. Unfortunately, when they expend energy, they do not burn the energy stored in that belly fat as well as younger people do. This leads to the buildup of increasing amounts of belly fat over time, which increases the risk of age-related diseases. The reason why older adults do not burn belly fat as well had been unknown until now.

The research team investigated the role of macrophages and how they relate to the fat-burning process. Typically, macrophages perform a variety of functions in the body, from mediating tissue repair to fighting infections and clearing up metabolic garbage.

During their study, the researchers discovered a totally new type of macrophage that resides on the nerves present in the stored belly fat. These nerve-associated macrophages get increasingly inflamed as we grow older due to a variety of age-related damages causing inflammation to rise system-wide. The more inflamed the nerve-associated macrophages become, the more they prevent the neurotransmitters, which are chemical messengers, from functioning properly.

The research team isolated the immune cells from the fat tissue of young and old mice, and they sequenced and computationally modeled the genome to better understand what was going on. They discovered that the aged nerve-associated macrophages can cause the breakdown of neurotransmitters known as catecholamines, thus preventing the fat cells from using their stored energy when the body needs it; in effect, the fat is locked into the body in limbo and is not used.

So how might science fix this problem?

The team discovered that when they reduced inflammation via a specific receptor that controls inflammation, the NLRP3 inflammasome, in the aged nerve-associated macrophages, the catecholamines were able to work efficiently again like they do in young mice. This shows clearly that the immune cells are communicating with the nervous system to control metabolism.

The research team then followed up by inhibiting an enzyme that increases in aged macrophages, thereby restoring fat metabolism in aged mice. The team observed that the enzyme, monoamine oxidase-A, or MAOA, is blocked by existing drugs for the treatment of depression. Therefore, MAOA-inhibiting drugs could potentially be used to improve metabolism in older adults, though more research is needed in order to specifically target the nerve-associated macrophages and to ensure the approach is safe.

The next step for the research team will be to further investigate the immune cells and how they interact with nerves and how crosstalk between the immune cells and nervous system relates to disease progression. The hope is that if controlling inflammation in aging nerve-associated macrophages can improve metabolism, it may have a wider positive effect on the nervous system or even on aging itself.


The reduction of inflammation is a key player in the aging process, and this is why research like this holds great potential for not only helping combat metabolic disorders but also for aging research. Also, the use of senolytics that remove senescent cells, a major source of systemic inflammation in aging, is possibly even more exciting; could reducing systemic inflammation improve these nerve-associated macrophages too?

It really should not need saying, but we do not suggest you take MAOA-inhibiting drugs to lose weight or slow aging as this is extremely dangerous. The researchers in this study have stressed that more research is needed to ascertain safety, so this is absolutely not something you should try at home, you have been warned. 


[1] Camell, C. D., Sander, J., Spadaro, O., Lee, A., Nguyen, K. Y., Wing, A., … & Rodeheffer, M. S. (2017). Inflammasome-driven catecholamine catabolism in macrophages blunts lipolysis during ageing. Nature550(7674), 119-123.

About the author

Steve Hill

Steve serves on the LEAF Board of Directors and is the Editor in Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 600 articles on the topic, interviewed over 100 of the leading researchers in the field, hosted livestream events focused on aging, as well as attending various medical industry conferences. His work has been featured in H+ magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, Swiss Monthly, Keep me Prime, and New Economy Magazine. Steve is one of three recipients of the 2020 H+ Innovator Award and shares this honour with Mirko Ranieri – Google AR and Dinorah Delfin – Immortalists Magazine. The H+ Innovator Award looks into our community and acknowledges ideas and projects that encourage social change, achieve scientific accomplishments, technological advances, philosophical and intellectual visions, author unique narratives, build fascinating artistic ventures, and develop products that bridge gaps and help us to achieve transhumanist goals. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project.
  1. jimofoz
    October 3, 2017

    Saw this recent article on research into converting white fat into brown fat:

  2. marianneabril
    June 27, 2020

    My problem is the opposite…..although l see life (in spite of many of its mysteries), as having meaning, difficult situations and events, and their subsequent stress, end up affecting me at a physical level and l end up losing weight through anxiety, but there is also the fact that l have a fast metabolism and burn food and calories fast. If l eat something that is not quite fresh or too “strong”, my body rejects straight away, all and all my tummy may round up a bit for a day or two, but it will soon get lean and flat……That may sound as ideal but l experience this close connection between my mind and my body, as making me vulnerable to losing weight easily as a response to life many crisis, and although l can put weight back on, with a bit of stability, it takes longer than losing it and affects my self-image, making me feel and look fragile, when in fact l would so much like for my outer self to reflect truly who l am inside and this fragility makes it difficult…….So you see, there are problems both ways in gaining weight easily as well as in losing it easily too.
    Thank you and all the best
    for all your projects.

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