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Inflammaging: a New Insight for Age-associated Diseases

The desire for an ideal appearance and to counteract signs of aging have motivated millions of individuals to seek out aesthetic treatments. Indeed, there is no denying that the demand for cosmetic procedures has had a significant increase in recent years. However, considering all the changes in the body that happen during aging, focusing solely on appearance can pose significant risks. Aging has been associated with the development of various persistent diseases (chronic diseases), including diabetes, cancer, and heart diseases, that cause death and disability worldwide (Ferrucci & Fabbri, 2018). During aging, an uncontrolled body defense reaction mechanism (persistent low-grade inflammation) develops, which contributes not only to the manifestation of age-related skin changes but also to the progression of age-related diseases throughout the body. However, there are ways to prevent this pro-inflammatory state over the course of the aging process, that can enhance the quality of life both in youth and old age. This article will describe a new concept that scientists have been studying called “inflammaging” and discuss possible mechanisms that may be linked to healthy aging.


Background and General Concepts

Aging is an undeniable reality for all living organisms and is a process that has captivated the attention of researchers from diverse fields of study who have dedicated their efforts to unraveling its mechanisms (Franceschi et al., 2000). While aging is often accompanied by the accumulation of experience, knowledge, and wisdom, it is also inevitably linked to a gradual deterioration in health and, ultimately, mortality. In scientific terms, aging is a complex process of becoming old that results from a combination of environmental and genetic factors. It is a phenomenon that involves a progressive decline in the body's functional abilities due to the progressive loss of cell functions and tissue renewal, leading to the body’s functional alterations (Lopez-Otin, Blasco, Partridge, Serrano, & Kroemer, 2013). These changes include a reduction in muscle mass and strength (reducing the ability to carry out daily activities and movements), reduced bone density (increasing the risk of fractures), diminished sensory abilities (loss of smell, taste, touch, sight, and hearing), impaired immune function (increasing susceptibility to infections), and decreased hormone production, leading to a higher risk of developing diseases (Figure 1).


Changes of aging in the body by organ system. CNS, central nervous system (Soto-Perez-de-Celis, Li, Yuan, Lau, & Hurria, 2018)

The term “inflammaging” was described by Franceschi et al in 2000 and has been used since then by researchers to define a state of low-grade chronic and persistent inflammation of the body that develops with age, leading to tissue degeneration (Franceschi et al., 2000). Inflammation is an acute vital reaction mechanism to threats and it is part of a beneficial defense system that maintains tissue equilibrium, but if uncontrolled it becomes deleterious, progressing to chronic inflammation (Figure 2). Chronic inflammation during aging is systemic, meaning it can affect every organ and tissue in the body, including the skin, kidneys, liver, lungs, brain, etc. In addition, it is persistent, which can be even more harmful to the body (Vasto et al., 2007).


Figure 2. Acute vs. chronic inflammation. Acute inflammation is a short-term response that occurs rapidly after tissue injury or infection while chronic inflammation is a long-term response that can persist for months to years. (Lorne et al. 2022)

Evidence indicates that chronic inflammation with advancing age (inflammaging) can precede several chronic diseases. Chronic diseases are the leading causes of death and disability worldwide: about 70% of all deaths are caused by these conditions (World Health Organization [WHO] 2022). While chronic diseases may not be curable, they can be treated and, more importantly, prevented. In the following sections, we will explore the mechanisms involved in the inflammaging process and discuss existing evidence on preventive measures.


Inflammaging Mechanisms and the Development of Chronic Diseases

Persistent inflammation is usually considered a biomarker of biological aging or even a mechanism by which the aging process is linked with increased susceptibility to diseases (Ferrucci & Fabbri, 2018). But how does inflammaging contribute to the development of chronic diseases?

The low-grade persistent inflammation state, a characteristic of inflammaging, results in the generation of free radicals, which are highly reactive molecules that promote cell damage and deterioration in organs (Kirkwood & Kowald, 2012). In an inflammatory environment, mechanisms of repair and maintenance that constantly occur in all tissues are compromised, leading to the accumulation of injured cells. Consequently, this effect can increase the production and elevate blood levels of pro-inflammatory molecules maintaining their persistent levels in body tissues and increasing the chances for multimorbidity (the number of coexisting diseases), a condition that is very common in aging. Another effect of inflammaging is the accumulation of senescent cells, which are “old cells” that are no longer able to divide, which means they do not promote tissue regeneration (repairing of damaged tissue), contributing to tissue aging and secretion of inflammatory molecules (Sanada et al., 2018). Thus, this low-grade chronic inflammation in old age contributes to the development and progression of several diseases (Figure 3) including cardiovascular diseases, chronic kidney disease, cancer, depression, dementia, osteoporosis (progressive bone loss), sarcopenia (loss of muscle mass), and anemia. There is strong evidence that typical geriatric conditions such as physical and cognitive disability, frailty, and premature death are also associated with inflammaging (Ferrucci & Fabbri, 2018).


Figure 3. Inflammaging is a risk factor for most serious chronic diseases and disabilities observed in elderly people. (Ferrucci & Fabbri, 2018)

Preventing Inflammaging

The concept of healthy aging has emerged from individuals in Europe who manage to reach advanced age while experiencing minimal inflammatory consequences typically associated with the aging process. The WHO defines healthy aging as maintaining a functional ability that enables individuals to meet their needs and contribute to society within their environment (Menassa et al., 2023). Studies have shown that genetic, environmental, and cultural scenarios influence the outcome of the aging process. Although studies reported that genetic effects can be related to inflammaging, evidence suggests strong involvement of environmental factors and lifestyle (Bektas, Schurman, Sen, & Ferrucci, 2018). Extensive investigations have identified practical approaches that enable the reduction of chronic inflammation's severity or even the reversal of its progression through lifestyle modifications. It has been well established that lifestyle changes including incorporating regular exercise, maintaining a balanced diet, managing weight effectively, ensuring sufficient quality sleep, reducing stress levels, and abstaining from tobacco and alcohol consumption are recognized as pivotal measures in reducing a pro-inflammatory state within the body and mitigating the signs of aging (Figure 4). All these factors together reduce body inflammation, improving overall quality of life and well-being by reducing the release of free radicals and inflammatory mediators, improving metabolism, and increasing tissue repair (Gronek et al., 2021; Margina et al., 2020; Marsman et al., 2018).


For a person who has maintained healthy habits throughout their life, the chances of developing chronic diseases are considerably reduced. A healthy lifestyle can help to circumvent some changes intrinsic to the aging process. For example, studies have shown that the aging process is associated with changes in the microbial composition of the gut (O'Toole & Jeffery, 2015). A correlation between microbial diversity, frailty scores, and environmental factors, such as dietary patterns, in elderly individuals has been described (Claesson et al., 2012). The adoption of a fiber-rich diet among the elderly can be extremely important as the metabolization (digestion) of dietary fiber generates short-chain fatty acids, molecules that facilitate the growth of beneficial bacteria in the gut while inhibiting the growth of pathogenic bacteria. This, in turn, helps reduce the production of inflammatory mediators, thus promoting a healthier gut environment and preventing the development of chronic diseases (Figure 4).


Figure 4. Preventing inflammaging involves changes in lifestyles. Adjustments in lifestyle, including regular exercise, a balanced diet, body weight control, quality sleep, and low stress, can prevent the development of chronic diseases. CVD, cardiovascular disease. NAFLD is a non-alcoholic fatty liver disease. T2D, Type 2 diabetes. (Nitschke et al., 2022)

In addition, engaging in regular physical exercise, coupled with a nutritious diet and effective stress reduction practices, plays a pivotal role in preventing or mitigating a highly prevalent chronic condition of our time: obesity. In many individuals, the aging process has been linked to the accumulation of visceral fat tissue, as well as the development of insulin resistance (Ahima, 2009). Insulin resistance refers to a diminished ability of cells to take up glucose from the bloodstream, consequently disrupting blood sugar levels and contributing to the development of obesity. Elevated levels of glucose and free fatty acids (elevated in most obese individuals especially due to a high-fat diet), induces the production of inflammatory molecules and increases the risk of developing other chronic diseases such as diabetes, cardiovascular diseases, and osteoarthritis, a painful degenerative joint disease (Ellulu, Patimah, Khaza'ai, Rahmat, & Abed, 2017). The combination of physical exercise and a healthy diet, on the other hand, can increase insulin sensitivity, preventing the pro-inflammatory state associated with obesity in elderly people.


Conclusions

Population aging is an undeniable demographic phenomenon, which is accompanied by a high prevalence of chronic diseases among individuals that goes far beyond physical appearance. This process represents a public health problem and a biological challenge. It's worth noting that while inflammaging is a recognized concept in the field of aging research, it's important to continue studying and understanding the underlying mechanisms and potential interventions to address this phenomenon effectively. Advancements in our understanding of this field hold significant potential for delivering important solutions, including the prevention of age-related diseases and the development of more effective therapeutic alternatives. Such progress would enhance the quality of life for older individuals and pave the way for healthy aging practices.



References

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Visual Sources


Figure 1: Soto-Perez-de-Celis, E., Li, D., Yuan, Y., Lau, Y. M., & Hurria, A. (2018). Functional versus chronological age: geriatric assessments to guide decision making in older patients with cancer. Lancet Oncol, 19(6), e305-e316. [image] doi:10.1016/S1470-2045(18)30348-6


Figure 2: Lorne J. Hofseth, James R. Hébert, (2022). Chapter 3 - Diet and acute and chronic, systemic, low-grade inflammation, Diet, Inflammation, and Health, 85-111. [image] doi: 10.1016/B978-0-12-822130-3.00011-9


Figure 3: Ferrucci, L., & Fabbri, E. (2018). Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty. Nat Rev Cardiol, 15(9), 505-522. [image] doi:10.1038/s41569-018-0064-2


Figure 4: Nitschke, E., Gottesman, K., Hamlett, P., Mattar, L., Robinson, J., Tovar, A., & Rozga, M. (2022). Impact of Nutrition and Physical Activity Interventions Provided by Nutrition and Exercise Practitioners for the Adult General Population: A Systematic Review and Meta-Analysis. Nutrients, 14(9). [image] doi:10.3390/nu14091729


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