Anti-Inflammatory Properties of Diet: Role in Healthy Aging

Inflammation is a physiological process involved in the defenses of the body and the repair of tissues. It is acutely activated by infections, trauma, toxins, or allergic reactions. However, if it becomes chronic, inflammation can end up stimulating the development of diseases such as cardiovascular disease, autoimmune disease, neurological disease, or cancer. Additionally, during aging, inflammation becomes increasingly more chronic. Furthermore, we found that certain foods, such as saturated fats, have pro-inflammatory activity. Taking this into account, in this review we have discussed different diets with possible anti-inflammatory activity, the commonly ingested components of each diet and their active compounds. In addition, we have proposed some dietary guidelines, as well as a list of compounds present in foods with anti-inflammatory activity, outlining how to combine them to achieve optimal anti-inflammatory effects. Therefore, we can conclude that the compounds in our diet with anti-inflammatory activity could help alleviate the inflammatory processes derived from diseases and unhealthy diets, and thereby promote healthy aging.


Diet and Inflammation
To understand the possible anti-inflammatory properties of diet on health and aging, it is necessary to perform studies that analyze the effects of dietary patterns on a specific population. Analyzing the relationship between a diet with the pathophysiology of different diseases is complicated. The focus of current research lays not only on the role of single nutrients and foods, but also on the compilation and the entire process from food production to food consumption [7]. The general idea is that food items show either synergistic or antagonistic effects when consumed in combination.
The dietary inflammation index (DII) was developed to enable the analysis the pattern of a whole diet on inflammation markers circulating in blood plasma [8]. According to the DII, some diets could be classified as pro-inflammatory or anti-inflammatory. Although it is true that in industrialized countries, we find individuals with more or less healthy diets, the main recognized pro and anti-inflammatory diets whose characteristics are discussed below ( Figure 1). The MD is defined through its ingredients, methods of conservation and culinary processes, which are passed on through generations before the globalization of the food system. The MD is described in civilizations that surround the Mediterranean Sea because they share common foods and cooking methods that comprise the dietary pattern. Differences in culture, religion and economy explain some variations, but the commonly regularly consumed ingredients include, olive oil, legumes and nuts, unrefined cereals, fruits vegetables, moderate consumption of fish, seafood and dairy products, low consumption of alcohol and a limited use of red and processed meat.
The long-term health benefits of MD have been widely studied thanks to the PRED-IMED study, a multicenter, randomized, primary prevention trial [22]. Olive oil is especially emphasized due to its ability to reduce radical oxidative species (ROS) and prevention of inflammation related diseases due to its phenolic compounds [23]. In a multicenter trial performed in Spain, 7447 participants between the ages of 55 and 80 with high cardiovascular disease (CVD) risk were assigned one of three diets: MD with extra-virgin olive oil, MD with nuts, or a control diet of reduced fat intake. After a 5-year period, both groups following a MD showed lower risk of cardiovascular events by 1.7-2.1%, whereas the low-fat diet control group showed no significant improvements. Authors attributed the protective role shown by MD to their antioxidants and anti-inflammatory components [24]. There is a similar study where 165 high CVD risk participants were assigned the same three diets. After 3 and 5 years, both groups following the MD had significant reductions of the inflammatory markers CRP, IL-6, TNFα, and monocyte chemoattractant protein 1 (MCP-1) in plasma by ≥16% [25]. Lopez-Moreno et al. developed a new randomized cross-over study where 20 healthy older adults were assigned three diets: a MD enriched with virgin olive oil, a diet rich in saturated fatty acids, and a low-fat high-carbohydrate diet enriched with ω-3 polyunsaturated acids. After a 3 week period, the postprandial intestinal absorption of lipopolysaccharides (LPS) in the low-fat diet increased inflammatory response compared with the MD [26].
Different studies have shown a direct relationship between arachidonic acid (AA) levels and chronic inflammation, a condition that occurs in obesity and liver disease [27]. Tutino et al. studied the effects of a MD or control diet, alone and in combination with physical activity programs, on the arachidonic/eicosapentaenoic acid ratio (AA/EPA), a common biomarker used to evaluate inflammation, in 146 patients with nonalcoholic fatty liver disease. Significant reduction in AA/EPA ratio were observed both at 45 and 90 days in the group assigned a MD combined with an aerobic activity program, while improvements were observed only after 90 days in the group assigned a control diet and the same activity program [28].
The apparent anti-inflammatory action of MD has been validated in more clinical trials with subjects with different characteristics. In a randomized controlled trial, 99 volunteers with osteoporosis were randomly assigned into groups of intervention (n = 50) and control (n = 49). The intervention group were asked to follow a MD, and after the 16 week trial they showed significantly decreased levels of the pro-inflammatory cytokine IL-1α [29]. Another small scale randomized clinical trial was performed in 34 participants of nonrestricted MD and 31 participants following a low-fat diet. Those following the MD had reduced subcutaneous fat and waist circumference after the 6 month period, which discounts the misconception that diets high in fats lead to weight gain [30].
The microbiota can modulate changes in aging related to innate immunity, sarcopenia, and cognitive function, which are essential components of the frailty syndrome through nutrition we can modify the microbiota to maintain intestinal health by stimulating beneficial bacteria [31]. In a parallel 8-week randomized controlled trial, 82 overweight and obese subjects without underlying diseases were separated into two groups. Forty-three subjects were set to follow a MD tailored to their habitual energy intakes, and 39 subjects maintained their regular diets. After the 8 week period, a significant increase in gut microbial gene richness and lower levels of serum hs-CRP was found in the diet intervention group, whereas no changes were found in the control group [32]. Changes in the microbiota with apparent anti-inflammatory effects have been also found in another recent clinical trial, where the microbiota of 612 nonfrail or pre-frail subjects across five European countries (UK, France, Netherlands, Italy, and Poland) was profiled before being administered a tailored MD tail. After a 12-month period, the enrichment of the microbiome taxa was associated with lower frailty markers, CRP, and interleukin-17 [33]. In another small-scale trial, 65 participants with diagnosed coronary heart disease were randomly assigned a MD or a low-fat diet intervention for 6 months. In the 56 subjects that completed the trial, the dietary inflammatory index was significantly reduced, through reductions in high sensitivity interleukin-6 and triglycerides levels [34]. Similarly, in a study with type 2 diabetes patients, the MD intervention group showed improved endothelial function and reduced CRP and ICAM-1 fasting blood levels after the 3 month trial [35].
The anti-inflammatory effects of MD, according to the referred results found in clinical trials performed in the last 5 years, are unquestionable. However, even though the health benefits of the MD have been known around the world for many years, adherence to this diet has been difficult for Western communities. Disadvantages are the limited availability and variety of ingredients outside of the Mediterranean area, higher costs, and a lack of familiar tastes [36]. To provide a healthy and easy-to-follow diet for the populations of different locations multiple diet pattern have been constructed. Other researched diet designs, such as the Nordic diet, traditional Asian diets such as the Japanese and Tibetan ones, have been put to focus and are also associated with a reduced risk of cardiovascular disease and other inflammatory-derived diseases [37].

Nordic Diet (ND)
Similar to the MD, the Nordic Diet (ND) focuses on the consumption of fruits and vegetables, which are replaced with local grown ingredients, such as berries, apples, pears, carrots, potatoes, cabbages and whole grain products, local fish products, the restriction of saturated fats as well as red and processed meats. The olive oil as the main source for unsaturated fats of the Mediterranean diet is replaced with canola oil [38].
The anti-inflammatory characteristics of ND has also been studied. In 2019, Tuomainen et al. set out to investigate the association between whole grain derived compounds and metabolic health from blood samples of 163 participants of the SYSDIET study [39]. They found clear associations between the healthy Nordic diet and the inflammation biomarkers IL-1 receptor agonist and CRP. Furthermore, Roager et al. showed how a whole grain diet significantly decreases IL-6 and CRP in 60 Danish adults with metabolic syndrome risk in an 8-week randomized cross-over trial [40].
In another substudy of the SYSDIET study, 88 patients with metabolic syndrome were assigned a ND or control diet consisting of low-fiber cereal products, milk fat, and restricted amounts of fish and berries. After a 18-24 week period, the expression level of the gene TNF-receptor superfamily member 1A was downregulated, although the NF-κB subunit, RELA proto-oncogene, was up-regulated in the intervention group [41]. Leder et al. evaluated whether the ND can modify the expression of inflammation-related genes in peripheral blood mononuclear cells by performing a 2 h oral glucose tolerance test in 89 participants from the SYSDIET study from three Nordic centers. They found significant downregulation of toll-like receptor 4, IL-18, and CD36 and upregulated expression of peroxisome proliferator-activated receptor delta (PPAR-δ) in the Nordic diet group compared to the control group [42].
The health benefits of ND recently gained interest in the scientific community, and therefore, the number of clinical trials performed is low compared to those performed with MD. However, the results found are very promising and point to an anti-inflammatory role of different components of this diet.

Asian Diet Japanese Traditional Diet: Washoku
Japan is known for its exceptionally healthy diet and extended longevity. In fact, Okinawa, the islands at the southern of Japan, is one of the seven blue zones and was once called the land of immortals. The traditional Japanese diet (Washoku) is characterized by high consumption of many types of fish, rich in EPA and docosahezaenoic acid (DHA), and soybean products and low consumption of animal fat and meat. The use of umami to enhance their recipes palatability avoids the consumption of refined sugar and salt. Steaming, boiling, and stewing are the main cooking methods in this diet, and therefore, their dishes are rich in water and low in fat, and subsequently have low-calorie density. The portion sizes usually are small, and seasonally available vegetables are typically used [43].
The effects of Japanese diet on inflammation have been studies through different clinical trials. An example is the work developed by Coe et al. who studied the blood samples of 382 middle aged and elderly adults in Japan to determine the effects of Japanese diet customs, with special emphasis on tea, vegetable, and seafood consumption. They found that the consumption of a Japanese diet was associated with significantly lower IL-6 and CRP levels [44]. Additionally, another study also found that subjects following a Japanese diet had decreased HbA1c levels compared to a control group already after 2 weeks. VFA levels, which have been shown to be associated with inflammation and CRP levels, were also decreased, possibly via the suppression of glucose-dependent insulinotropic polypeptide [45][46][47].
Despite the benefits of the traditional Japanese diet, like the forementioned diets, this also has become Westernized over the past decades and consequent disease rates have risen. A small-scale randomized controlled trial in 21 subjects was performed to evaluate the effects of the modern and traditional Japanese diets. The researchers found that the 1975 Japanese diet decreases bacteria associated with lifestyle diseases in 11 subjects compared to the 10 subjects following a modern Japanese diet for 28 days. Four genera, including Parabacteroides were changed in the 1975 diet group, which are known to promote inflammatory bowel disease. HbA1c, which is correlated with inflammation, was also decreased on those following the 1975 diet [48,49].

Chinese Traditional Diet: Jiangnan Diet
Finally, although it has not been studied deeply yet, the characteristics of a traditional Chinese based diet, the Jiangnan diet, used in some regions of China nowadays, are worth mentioning.
The dietary patterns and nutrition composition of the Chinese diet have changed considerably from the 80s, becoming increasingly more Westernized [50]. The consumption of refined grains, red meat, processed meat, and sugar-sweetened beverages has increased, and, furthermore, frying is more used for cooking than the traditional boiling or steaming. Consequently, the prevalence of chronic noncommunicable diseases (NCDs), including obesity, diabetes, CVD, and cancers, have increased [51,52]. However, there seems to be differences between the Northern regions and a region in the South of China, where obesity and metabolic syndrome prevalence are lower in the latter. This difference has been associated to the diverse dietary pattern between the two regions [50]. In the South of China, reminiscences from traditional Chinese food patterns remain and steaming or boiling are the preferred cooking procedures. Furthermore, in that zone there is a higher consumption of vegetables and fruits in season, fresh fish, legumes, moderate consumption of whole-grain rice, plant oils (mainly rapeseed oil), and red meat, and relatively low consumption of salt. The consumption of soy-derived products is also common in this region.
The anti-inflammatory properties of Jiangnan Diet have not yet been studied, but according to their ingredients and methods of cooking, as well as the epidemiologic data, it is very promising. Nevertheless, more investigation to confirm its beneficial effects on health is necessary.

Classification
The anti-inflammatory properties of the diets discussed above are due to the presence of compounds in the most commonly ingested foods of each region. These properties are mainly attributed to phenolic structures present in fruits and vegetables, and to a lesser extent in cereals, legumes, and fish. Table 1 shows different compounds with antiinflammatory activity and the foods with the highest proportions. To explain the mechanism of action through which the selected anti-inflammatory compounds run their function, we have classified them according to their chemical structure.
Other bioactive lipid mediators generated from EPA and DHA metabolism through COX and LOX enzyme pathways are called resolvins (Rvs), protectins (PDs) and maresins (MaRs). They have anti-inflammatory and inflammation resolving effects, as well as immunoregulatory actions on T and B cells to promote the resolution of inflammation. E-series resolvins are produced from EPA, and D-series resolvins, protectins and maresins are produced from DHA.
ω-3 PUFAs also have an impact on lipid rafts formation that act as signaling platforms and protein recruitment sites. Lipid rafts are rich in cholesterol, for which ω-3 PUFAs have low affinity. Thus, instead of direct incorporation of dietary PUFAs into the lipid rafts, they incorporate into other regions of cell membranes from where they seem to influence lipid rafts function and formation, hampering protein recruitment and cell signalling [69].
In addition to the abovementioned biochemical competition, another mechanism of the ω-3 involves the NF-κB, a crucial transcription factor in inflammatory responses that upregulates the expression of a variety of proteins involved in the inflammatory processes ( Figure 2), including chemokines and cytokines (such as TNF-α, IL-1β, IL-6, IL-8, IL-12p40, MCP-1, MIP-1), adhesion molecules (ICAM-1, VCAM-1, selectins), enzymes (COX-2, iNOS) and platelet activating factor. The NF-κB transcription factor is localized in the cytosol associated with inhibitor proteins IκBs as an inactivated trimer. The phosphorylation of the inhibitory subunit IκB by IκB Kinases (IKKs) triggers its dissociation and translocation of the remaining active dimeric NF-κB to the nucleus, activating pro-inflammatory target genes [70,71].

Phenolic Compounds and Polyphenols
Phenolic compounds are a large heterogeneous group of molecules widely distributed in nature. Polyphenols and phenolic compounds are an important group of secondary metabolites, found in plants, including fruits and vegetables, tea, coffee, chocolate, herbs and spices, whole grains, edible mushrooms and fungal fruiting bodies, and red wine. Phenolic compounds are classified according to their chemical structure, based on the number of aromatic rings with attached hydroxyl groups (Figure 3). Numerous in vitro and in vivo studies highlight their antioxidative and antiinflammatory properties, flavonoids being the most studied polyphenols [76][77][78]. They exert these properties through different mechanisms, including antioxidant activity restoration, inhibition of pro-inflammatory enzymes, and modulation of mediators and transcription factors involved in inflammatory processes [79]. Although the precise mechanisms of action of phenolic compounds have not been fully dilucidated, a correlation between the high intake of phenols and polyphenol-rich food and a downregulation of inflam-matory processes have been found [80]. Therefore, a high enough daily intake of this group of compounds could ameliorate inflammaging and inflammation associated with chronic diseases.
Phenolic compounds exert their anti-inflammatory properties through multiple ways, such as inhibiting the activity, gene expression or synthesis of pro-inflammatory mediators. They act on COX-2, iNOS, and eicosanoids, thereby inhibiting the immune cell activation, modulating transcription factors, like NF-KB or Nrf-2, which result in anti-inflammatory and antioxidant effects [80]. In addition to a reduction of pro-inflammatory markers, such as IL-1β, 1L-6, TNF-α, phenolic compounds also lower LDL oxidation, leading to a decreased vascular inflammation, risk of platelet aggregation, and a reduction in oxidative stress and nitric oxide (NO) effects [80]. Figure 4 summarizes the anti-inflammatory properties of these compounds. As previously mentioned, the arachidonic acid released from the cell membrane phospholipids by PLA2 is metabolized by COX and LOX enzymes to prostaglandins, thromboxanes and leukotrienes. Flavonoids can inhibit the enzymatic activity of PLA2, COX and LOX enzymes as well as inhibit protein expression of COX and LOX, quercetin being the first flavonoid described to inhibit PLA2 in human polymorphonuclear leukocytes. Flavonoids can also interfere with signaling pathways, including protein kinase C, NF-KB and tyrosine kinase pathways, leading to the suppression of COX gene expression, though the inhibiting mechanisms of the enzymatic activity have not been fully elucidated [81,82]. Flavones like apigenin and luteolin, flavonols, isoflavones like genistein, flavanols like catechin, among other examples gathered in Table 2, have also demonstrated the capacity to inhibit COX and/or LOX enzymes both in in vitro and in vivo models [82]. Furthermore, NF-κB activation, iNOS expression, NO production, aldosterone signaling, and gene expression induced by aldosterone and cytokines production (TNF-α, IL-1β) can also be inhibited by flavonols like kaempferol [80].
The anti-inflammatory properties of phenolic and polyphenolic compounds can also be attributed to their antioxidant activities. Flavonoids exert antioxidant activities by scavenging ROS generated by neutrophils and macrophages and inhibiting the ROS-producing enzymes NADPH oxidase, xanthine oxidase and myeloperoxidase [82]. Additionally, flavonoids can activate Nrf2 signaling pathway [81], thereby exerting an anti-inflammatory role. Nrf2 binds to antioxidant responsive elements (AREs), thus activating expression of genes such as HO-1, which directly inhibits pro-inflammatory cytokines and activates anti-inflammatory cytokines. HO-1 also catalyzes the heme into free iron, biliverdin and carbon monoxide (CO); CO inhibits NF-KB pathway. Thus, Nrf2 leads to a decreased expression of pro-inflamamtory mediators and enzymes (COX, LOX, iNOS). Nrf2 inhibits cytokines and chemokines production, including TNF-α, IL-1β, IL-6, IL-17, MPC1, MIP2, as well as inhibits gene expression of CAMs induced by these cytokines [83].
As briefly explained in previous sections, inflammatory responses are regulated by proinflammatory mediators secreted by macrophages, including cytokines such as IL-1β, IL-6, TNF-α and the enzymes COX-2 and iNOS that produce PGE2 and NO, respectively. NF-κB is the main transcription factor involved in inflammatory processes, which translocates to the nucleus after phosphorylation of IκB, activating the expression of pro-inflammatory genes [71]. Terpenes and terpenoids exert their inflammatory actions through reducing activity of NF-κB pathway, thus ameliorating expression of pro-inflammatory mediators [77,84].
Moreover, terpenes may induce PPARγ, a transcription factor that promotes antiinflammatory responses and resolution of inflammatory processes, by acting like PPARγ agonists, thereby inhibiting the expression of pro-inflammatory cytokines and promoting immune cells polarization toward anti-inflammatory phenotypes [84,87].
Another target that several compounds listed in the Table 2 have in common is the mitogen-activated protein kinase (MAPK) family. MAPK pathways are activated by primary inflammatory stimuli and cytokines, including TNF-α and IL-1β, through TLRs, TNF receptors (TNFR) or IL-1 receptor (TIR). The NF-κB pathway and several inflammatory mediators are regulated by MAPK cascades, which are activated by phosphorylation. JNK is involved in iNOS expression and AP-1 activation through c-Jun subunit phosphorylation; ERK promotes iNOS expression, IKK activation and production of several cytokines, including TNF-α; and p38 MAPK leads to iNOS production and the expression of proinflammatory mediators such as COX-2, IL-1β, TNF-α, IL-6 and, IL-8 [88,89]. Figure 5B summarizes the anti-inflammatory mechanism of action of these compounds, and Table 2 summarizes all the aforementioned anti-inflammatory compounds with their mechanisms of action.  Reduction in phosphorylation and activation of TAK1 and NF-κB Decreased TNF-α production Activation of GP120, thus blocking IKK-β/NF-κB pathway by retaining TAB1 through β-arrestin-2 TNF-α-stimulated rHypoE-7 cell line from the embryonic rat hypothalamus

Bioavailability
The anti-inflammatory capacity of these compounds has been mostly studied in vitro, without considering the possible effects human digestion and metabolism could have on their anti-inflammatory potential. For example, flavonoids are metabolized by conjugation reactions, such as glucuronidation, methylation or sulfation in the small intestine and liver. Flavonoids in their non-glycosylated form (aglycones) can be absorbed directly by passive diffusion in the small intestine, while their glycosylated form must be hydrolyzed by intestinal enzymes or microflora [122]. Furthermore, there are differences in the immunomodulation exerted by glycosylated forms of flavonoids and their corresponding aglycones [123]. Regarding omega 3 fatty acids, they are present in fish as free fatty acids and linked to triglycerides. Lipases hydrolyze glycerol and free the fatty acids that can be absorbed by simple diffusion in the presence of bile, and therefore the bioavailability of these fatty acids is very high [56].

An Anti-Inflammatory Dietary Pattern: What and How Much to Eat
We have described in the previous section that the most important anti-inflammatory components present in diet are ω-3 PUFA, phenolic compounds and terpenes/terpenoids. They can be found in a large variety of products which are usually consumed in MD, ND, Washoku, and other diets considered as healthy and potentially anti-inflammatory.
However, in order to obtain the benefits of these molecules, they should be consumed in high enough quantities. For instance, only high doses of EPA and DHA-at least 2 g per day-have achieved anti-inflammatory effects in humans [75]. In fact, data from a doseresponse study in healthy participants with an EPA-rich supplement showed that an EPA intake of 1.35 g/day for 3 months was not sufficient to influence ex vivo PGE2 production by LPS-stimulated mononuclear cells, whereas an EPA intake of 2.7 g/day significantly decreased PGE2 production. This study suggests a threshold for an anti-inflammatory effect of EPA of somewhere between 1.35 and 2.7 g EPA per day [75]. Furthermore, combined intakes of EPA and DHA in the diet are preferred because this leads to an enrichment in EPA and DHA content in the cell membranes in a time-and dose-dependent manner and a decrease in AA content. In this sense and taking as reference an average content of 2300 mg of ω-3 PUFA (considering the sum of DHA, EPA, DPA ω-3 and Linolenic acid) present in 100 g of mackerel, a fish frequently eaten in the Mediterranean area and Nordic regions, a portion of 150 g/day would cover the quantity of the ω-3 fatty acids needed to exert their anti-inflammatory properties. Furthermore, mackerel provides a ratio of ω-3 PUFA/n-6 PUFA of 6.1. This portion size of 150 g of salmon would also cover that quantity of ω-3 PUFA maintaining a good ω-3 PUFA/ω-6 PUFA ratio of 5.4.
Cacao is a major source of flavonoids. Dark chocolate (cacao% > 70%) provides a large quantity of cacao and is therefore a good source of these phenolic compound, particularly of ferulic acid, quercetin, epicatechin and catechin, and resveratrol. However, the quantities of each of these molecules necessary to act as anti-inflammatory players individually would imply the intake of huge quantities of dark chocolate. For instance, ferulic acid has demonstrated a statistically significant reduction in the inflammatory markers hs-CRP and TNF-α by using a dose of 1000 mg/day, which would mean eating six bars of dark chocolate daily. However, since cocoa and dark chocolate exhibit a combination of different phenolic compounds, several clinical trials with daily intakes between 30-50 g of dark chocolate (1/3 bar) has shown reduction in hs-CRP, TNF-α and IL-6 and an increase in the anti-inflammatory marker IL-10 [124,125].
Because obtaining the anti-inflammatory quantity of each compound through the intake of only one food is not possible, the most reasonable strategy is combining the intake of several foods rich in them. For instance, the combination of different vegetables such as aubergine, artichoke and celery spiced up with olive oil, vinegar, rosemary, oregano or cumin provides ferulic acid, kaempferol, caffeic acid, apigenin, gallic acid and carnosol. Keeping this in mind, we have proposed an example of a one-day anti-inflammatory diet based on five meals ( Table 3). The total content of anti-inflammatory compounds provided by this diet is outlined in Table 4.
It is important to bear in mind that the diet must be adapted to the tastes of each individual because the enjoyment of meals is key. On the other hand, when we eat foods with a certain pro-inflammatory activity, such as red meat or products rich in animal fat, it is important to combine them with foods that can counteract this damage, such as salads and fruits or by drinking tea or red wine, that contain anti-inflammatory compounds.   Table 4. Anti-inflammatory compounds present in the outlined meal plan in Table 3.

Inflammation, Oxidative Stress, and Hormesis
Chronic pathologies are normally presented by inflammation and oxidative stress due to a dysregulation caused by an increase of free radicals and pro-inflammatory factors. Their relationship is thought to begin with an increase in oxidative stress that ends up stimulating the activation of inflammatory factors which, when chronic, affect the progress of the pathology even more negatively (Oxidative Stress, Inflammation, and Disease Shampa Chatterjee). In this review, we have discussed the ability of different compounds present in diet to reduce inflammatory processes, not only by reducing the presence of proinflammatory products but also by promoting the presence of anti-inflammatory factors.
Some authors such as Edward J. Calabrese et al. postulated the hormetic effect of chemical compounds more than 30 years ago. They observed how small damaging stimuli at the cellular and tissue level triggered a protective response that positively affected DNA repair, life span or tumor incidence (the occurrence of chemically induced hormesis). The hormetic effect has gained interest over the years, and it is being postulated that the possible mechanism of action of some polyphenols against neurodegenerative pathologies such as Parkinson's or ALS is due to this phenomenon (Calabrese et al., 2010, Antiox Redox signal 13,1763;) (Siracusa et al., Antioxidants 2020, 9 (9): E824) (Demonstrated hormetic mechanisms supposedly serve the effects induced by riluzole in neuroprotection against amyotrophic lateral sclerosis (ALS): Implications for research and clinical practice). In fact, it appears that stimuli that produce mild inflammation triggers an increase in the production of anti-inflammatory compounds (Aging and Parkinson's disease: inflammation, neuroinflammation and biological remodeling as key factors in the pathogenesis).
Eating lots of fruits and vegetables can improve health, and many people will point out the antioxidants in these foods. This reasoning is logical because it seems that diseases such as cancer, cardiovascular disease or diabetes involve cell damage caused by free radicals that antioxidants neutralize. However, the story of antioxidants is not that simple. In fact, there are controlled trials in animals and humans with antioxidant vitamins C, E, and A that have failed to prevent or ameliorate disease. Thus, how do fruits and vegetables support health? Plants have developed strategies to protect themselves over millions of years and also to promote the health of who or what propagates them. The bitter-tasting chemicals made by plants act as natural pesticides. When we eat plant-based foods, we consume low levels of these toxic chemicals, which causes low levels of stress in the body's cells, in the same way that exercise or lack of food over long periods of time do. The cells do not die; in fact, they become stronger because their stress response strengthens their ability to adapt to increased levels of stress. This process is called hormesis and could be the possible mechanism of action of why vegetables exert beneficial effects on our health (Sci Am. 2015 July; 313 (1): 40-45.).

Conclusions
Inflammation is a key physiological process in immunity and tissue repair. However, during aging it becomes increasingly more chronic. In addition, we found that certain foods such as saturated fats have pro-inflammatory activity. Taking this into account, in this review we have proposed some dietary guidelines as well as a list of compounds present in foods with anti-inflammatory activity. It must be taken into account that the amounts used in the studies that detect anti-inflammatory activity of these compounds are very high, and the intake of a single food to achieve its anti-inflammatory power is not feasible. However, the combination of foods rich in compounds with anti-inflammatory activity could exert beneficial effects during aging and in pathologies associated with inflammation and in reducing the detrimental effects of foods with pro-inflammatory activity. Therefore, we can conclude that the compounds in our diet with anti-inflammatory activity could help alleviate the inflammatory processes derived from diseases and unhealthy diets, and thereby promote healthy aging. Thus, we can use diet not only for nourishment, but also as medicine.

Conflicts of Interest:
The authors declare no conflict of interest.