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Ageing and Curcumin – A scientific Study

Ageing is an accessory to decreasing health status and increasing probability to acquire age-related disease such as cancer, Alzheimer’s disease, atherosclerosis, metabolic disorders and others. They are likely caused by low grade inflammation driven by oxygen stress and manifested by the increased level of pro-inflammatory cytokines such as IL-1, IL-6 and TNF-α, encoded by genes activated by the transcription factor NF-κB. It is believed that ageing is plastic and can be slowed down by caloric restriction as well as by some nutraceuticals. Accordingly, slowing down ageing and postponing the onset of age-related diseases might be achieved by blocking the NF-κB-dependent inflammation.

The evolutionary theory of disposable soma suggests that ageing is unavoidable but malleable and plastic [23] and perhaps this may be possible by dietary or pharmaceutical intervention or genetic alteration, to extend the lifespan [22].

Among nutraceuticals, the role of curcumin is supported by a number of scientific evidence that have confirmed its anti-inflammatory and anti-oxidant actions both in vivo and in vitro. Curcumin is the phytochemical derived from the rhizome of Curcuma longa, present in the spice turmeric and it gives Indian curry its yellow color.

Curcumin has been used for millennia as a wound-healing agent and for treating a variety of diseases in traditional Indian and Chinese medicine. Recently, it has attracted the attention of researchers as an agent capable of inhibiting the proliferation of cancer cells and/or inducing many signaling pathways leading to various modes of cell death [24, 25]. As a cell death inducer curcumin has gained profound interest as a chemopreventive and anti-cancer agent which found confirmation in many in vitro experiments and preclinical studies on animal models.

Furthermore curcumin rises interest as an agent of potential use in therapy of many diseases (not only cancer) with an inflammation constituents including cardiovascular diseases, Alzheimer’s disease, rheumatoid arthritis and metabolic syndrome. Although only a few worldwide clinical trials are underway now [26], a plethora of studies using animal and cell line models have been undertaken to elucidate the molecular mechanisms and biological effects of curcumin.

Curcumin has an unprecedented number of molecular targets justifying its chemopreventive, antioxidant and anti-inflammatory activities (reviewed recently in [27, 28]. Briefly, these targets include transcription factors with AP-1 described as the first one, and others such as SP-1, p53, STAT-3, ATF3, Nrf2, PPAR-γ, CHOP, HIF-1α, β-catenin and NF-κB, enzymes such as protein kinases (PKA, PKC, FAK, Src), glutathione S-transferase, DNA topoisomerase-II, telomerase, heme-oxygenase-1, p300 histone acetyltransferase, metaloproteinases, lipoxygenase (5-LOX), cyclooxygenase-2 (COX-2) and others. The most far-reaching physiological consequences seem to stem from the action of curcumin as an inhibitor of the activity of the transcription factor NF-κB. The NF-κB transcription factor is a master regulator of the inflammatory process which activates the expression of many pro-inflammatory cytokines, such as TNF-α, IL-1β and IL-6. Some of the NF-κB-induced proteins, like TNF-α, are also its activators, which is particularly important in the chronic inflammatory state. NF-κB seems to be the culprit of inflammageing, since this signaling system integrates the intracellular regulation of immune responses in both ageing and age-related diseases [29].

Many activities of curcumin can be also explained by its ability to suppress acute and chronic inflammation by scavenging reactive oxygen and reactive nitrogen species and enhancing antioxidant defense (i.e. by increasing glutathione level). However, curcumin is not only a simple antioxidant, but as a electrophilic compound it triggers the Nrf2/ARE signaling pathway which plays a key role in activating antioxidative enzymes, phase 2 enzymes and so – called vitagens (heme oxygenase, Hsp70, thioredoxin reductase and sirtuins), which might have a pivotal role in oxidative stress-induced diseases [30].

The amount of data documenting beneficial effects of curcumin in protecting against different diseases, particularly those which are related to age are increasing. It seems that extraordinary potency of curcumin, which makes it an almost universal remedy, results from the inflammatory origins of many diseases and curcumin’s anti-inflammatory activity.

Despite the practical lack of data showing curcumin’s influence on ageing and lifespan, there is a strong rational argument suggesting that curcumin can influence the process of senescence and ageing retardation [25].

Curcumin and AD

Recently curcumin has been proposed as a potential remedy against brain ageing and neurodegenerative disorders [31], and it has been evaluated in a pilot clinical trial in AD patients, with encouraging preliminary results [32]. Curcumin is highly lipophilic and might cross the blood-brain barrier (BBB) to reach the brain. Although its bioavailability is very low, since the drug is rapidly metabolized by conjugation, curcumin may reach brain in a sufficient concentration to activate signal transduction events and to decrease Aβ aggregation [33]. Epidemiological studies suggested that curcumin, one of the most prevalent nutritional and medical compounds used by the Indian population, is responsible for the significantly reduced (4.4-fold) prevalence of AD in India compared to United States [34]. Furthermore elderly Singaporeans who ate curry with turmeric had higher Mini-Mental State Examination scores than those who did not [35].

Curcumin can counteract the pro-inflammatory state which is believed to participate in many age-related diseases. In fact, it seems that curcumin directly affects a few major targets, just like ROS scavenging and production and the NF-κB signaling pathways, which can in turn suppresses the pro-inflammatory state involved in the etiology of ageing and age-related diseases.

The main concern regarding the therapeutic value of curcumin is its poor bioavailability, which, on the other hand, assures lack of toxicity even when consumed in a daily dose of 8 mg. Moreover, the data so far collected, show that curcumin has a very high activity not only in in vitro experiments, but also at the organismal level. This could be explained by its hormetic activity [36]. Accordingly, it appears that curcumin is a very safe and beneficial nutraceutical spice which might fend off ageing and age-related diseases. However, at this time there is no data showing that any nutraceutical may influence ageing and lifespan, and complete randomized clinical trials in humans are also needed to confirm the potential use of curcumin in the prevention of diseases with an inflammation constituents, e.g. cardiovascular diseases, AD, cardiometabolic syndrome, and ageing.

https://immunityageing.biomedcentral.com/articles/10.1186/1742-4933-7-1

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