Multi-morbidity in the elderly

Multimorbidity is a significant area for research because it’s becoming more relevant as people live longer. Multimorbidity is the coexistence of several diseases in a patient at the same time. In the elderly, for example, it means that they’re suffering from several age-related maladies at once. 

Chronic obstructive pulmonary disease (COPD) provides a useful template by which we can study multimorbidity. Most people with COPD have comorbidities; in fact, 95% of COPD patients have two or more diseases concurrently. 

Mostly, these are also diseases of accelerated aging. These comorbidities include cardiovascular diseases like ischaemic heart disease, myocardial infarction, strokes, high blood pressure and heart failure. There are also metabolic diseases that include late-onset diabetes, metabolic syndrome, osteoporosis, chronic kidney disease and other diseases of aging, such as muscle wasting, Alzheimer’s disease and cancers, particularly lung cancer.

When these diseases occur in COPD patients, we call them comorbidities because we diagnose lung disease and say they have other conditions. However, a cardiologist may diagnose heart failure. Patients with heart failure commonly have COPD, so cardiologists would consider COPD a comorbidity. Overall, it’s better to think of these diseases clustered together as multimorbidity of aging.

MicroRNAs are very important molecules that can lead to accelerated aging. Importantly, microRNAs are packaged inside the cell into vesicles. Vesicles are little spheres surrounded by a membrane that are released from cells.

If you examine these vesicles from cells, the blood or the lungs, you find that they contain microRNAs. In COPD, we’ve shown that the cells lining the lung produce these little vesicles containing the microRNAs that cause senescence. These vesicles are absorbed by other cells, where they go on to induce senescence. In this manner, senescence spreads from cell to cell, which is why COPD is progressive.

These little vesicles are also able to spread outside the lung. They can get into the circulation and be distributed all around the body to other organs like the blood vessels. In particular, we’ve shown that if you look at cells that line blood vessels in COPD, they show reduced sirtuin 1 and accelerated aging via the same pathways we see in COPD. 

We think that this aging can spread from the lung to other organs and affect the heart and blood vessels. It can also lead to diabetes and chronic kidney disease. These messages circulate aging around the body, and this is how age-related diseases may be linked together as multimorbidity. If we could target these vesicles and block their contents, then maybe we could stop aging. 

An essential aspect of dealing with multimorbidity is guiding treatment, which may encompass several specialties. In a typical setting, general practitioners see patients with various diseases. As such, they’re in an excellent position to evaluate the different conditions that patients have and refer them to specialists if the disease is troublesome. The specialist will then usually look at their illness and treat that, but they may not consider the patient’s other conditions. 

In pulmonary medicine, we’re probably more used to looking at diseases outside the lung than other specialists. For example, in COPD, we routinely assess people’s heart function, whether they have diabetes etc., because we know that these are commonly seen in COPD. Nevertheless, it may be that other specialists, like heart specialists, wouldn’t be looking for COPD and may overlook it in those patients.

Geriatricians are specialists of old age. They are better equipped than most specialists to treat more severe patients because they specifically see elderly patients, and they’ve long recognised the importance of multimorbidity. Nevertheless, hospitals likely need to have more general practitioners than specialists who can evaluate many different diseases, particularly in the younger spectrum of multimorbidity. In short, we need to be more holistic in our assessment of patients.

When considering prevention, lifestyle issues are important. While some drug therapies are available, I think lifestyle changes are more critical because people sustain them more easily.

As I’ve mentioned, poverty is a significant risk factor for multimorbidity, which may relate to lifestyle. Poor people develop multimorbidity 10 to 20 years earlier than wealthy people. These people are exposed more to smoking, poor diet, poor home environments, stress and many different risk factors. These risk factors affect some diseases more than others. Smoking is more important for lung disease, whereas poor diet may be more important for heart disease and diabetes. Everything considered, a healthy lifestyle is obviously recommended, though challenging to achieve for more impoverished populations.

Nevertheless, I think that, from research on aging and related pathways, we have seen that there is a potential for dietary intervention in terms of prevention. In an earlier EXP, I mentioned resveratrol, which is found in red wine. There is epidemiological evidence that if people drink a moderate amount of red wine, they develop fewer age-related diseases like heart disease and cancer. This is known as the “French paradox” and is widely recognised. 

However, there are other dietary interventions. Fresh fruit, for example, provides antioxidants that counteract the oxidative stress that drives the aging process.  Green tea also contains substances that inhibit the aging pathway. Several other dietary factors, like vitamin D and selenium, which also reduce oxidative stress and inflammation, may be important. The healthiest diet is the Mediterranean diet, which contains less meat and more fish, fresh fruit and vegetables than other diets. This diet has been shown in experimental studies to reduce age-related diseases.  

So, I think lifestyle changes will become increasingly important once people understand the best way to apply these findings. One very interesting fact is that starvation has anti-aging effects while increasing sirtuin 1, the anti-aging molecule; but starvation and loss of calories are very difficult to sustain. You can do it in experimental studies, but not in people for long. Still, researchers are looking at intermittent starvation as a possible way of overcoming accelerated aging.