Curcumin: A Golden Approach to Healthy Aging: A Systematic Review of the Evidence

Abstract

Aging-related disorders pose significant challenges due to their complex interplay of physiological and metabolic factors, including inflammation, oxidative stress, and mitochondrial dysfunction. Curcumin, a natural compound with potent antioxidant and anti-inflammatory properties, has emerged as a promising candidate for mitigating these age-related processes. However, gaps in understanding the precise mechanisms of curcumin's effects and the optimal dosages for different conditions necessitate further investigation. This systematic review synthesizes current evidence on curcumin's potential in addressing age-related disorders, emphasizing its impact on cognitive function, neurodegeneration, and muscle health in older adults. By evaluating the safety, efficacy, and mechanisms of action of curcumin supplementation, this review aims to provide insights into its therapeutic potential for promoting healthy aging. A systematic search across three databases using specific keywords yielded 2256 documents, leading to the selection of 15 clinical trials for synthesis. Here, we highlight the promising potential of curcumin as a multifaceted therapeutic agent in combating age-related disorders. The findings of this review suggest that curcumin could offer a natural and effective approach to enhancing the quality of life of aging individuals. Further research and well-designed clinical trials are essential to validate these findings and optimize the use of curcumin in personalized medicine approaches for age-related conditions.

Keywords: Curcuma longa; aging; cardiovascular diseases; clinical trials; curcumin; frailty; inflammation; neurodegeneration; oxidative stress; sarcopenia.

Figure 1

The main parts of the Curcuma longa plant. (A): leaves; (B): flower; (C): rhizomes; (D): sliced rhizomes; (E): rhizome powder; (F): pharmaceutical formulation, and (G): curcumin molecular structure.

Figure 2

Flow diagram showing the study selection (according to PRISMA guidelines) [47].

Figure 3

Overview of the aging process. Cellular senescence triggers inflammatory processes and the release of pro-inflammatory biomarkers such as IL-1β, IL-6, TNF-α, IFn-γ, CXCL-1, and CXCL-12. Free radicals and reactive oxygen species induce the installation of oxidative stress (OS) that aggravates inflammation. On the other hand, inflammation aggravates OS, leading to a vicious cycle. Apaf-1: apoptotic protease-activating factor-1; Bax: Bcl-2-like protein X; BCL-2: B-cell lymphoma 2; CXCL: chemokine (C-X-C motif) ligand; IL: interleukin; INF-γ: interferon-γ; MDA: malonaldehyde; TNF-α: tumor necrosis factor-α. ↓: decrease; ↑: increase.

Figure 4

The effects of curcumin against inflammatory pathways. Curcumin inhibits the MAPK, ERK, p38, p65, p50, and NFkB pathways and the consequent release of pro-inflammatory cytokines such as interleukin (IL)-1; IL-12, and tumor necrosis factor-α (TNF-α). Besides that, curcumin also inhibits the Janus kinase/signal transducer and active factor of transcription (JAK-STAT) cascade. There is stimulation of Kelch-like ECH-associated protein 1 (Keap1) and nuclear factor erythroid-2 related factor 2 (Nrf2) that also interfere with pro-inflammatory pathways. ARE: antioxidant responsive elements;CXCL: chemokine (C-X-C motif) ligand; ERK: protein kinase RNA-like endoplasmic reticulum kinase; HO-1: Heme-oxygenase-1; IKB: IkappaB kinase; MAPK: mitogen-activated protein kinase; MCP1: monocyte chemoattractant protein-1; NF-κβ: nuclear factor-kappa beta,; NRLP34: NLR family pyrin domain containing; PPAR: peroxisome proliferator-activated receptor; RANTES: IL-8 superfamily cytokines; TLR4: Toll-like receptor. ↓: decrease.

Figure 5

Effects of curcumin on mitochondrial dysfunction and oxidative stress in different signaling pathways. Curcumin can upregulate sirtuin (SIRT), Ketch-like ECH-associated protein 1, nuclear factor erythroid-2 related factor 2 (Keap1-Nrf2), and Wnt/β catenin pathways, and inhibit nuclear factor kappa beta (NF-κβ). The results of the stimulation and inhibition of these pathways is the modulation of lipid peroxidation, oxygen consumption, aconitase and antioxidant enzyme modulation, and ATP production in mitochondria. Moreover, curcumin is related to the upregulation of the synthesis of glutathione peroxidase (GPX), superoxide dismutase (SOD), reduction of malonaldehyde (MDA), reactive oxygen species (ROS), and reactive nitrogen species (RNS). The results of curcumin effects are improvements in cardiovascular, renal, and hepatic diseases. Furthermore, there is a reduction in frailty, sarcopenia, and brain disorders. ↓: decrease; ↑: increase.

Figure 6

Curcumin and its effects on nervous system disorders. Activation of NOD-like receptor pyrin domain-containing 3 (NLRP3), Toll-like receptor 4 (TLR4), nuclear factor-kappa beta (NF-κβ), and triggering receptor expressed on myeloid cell 2 (TREM2) is associated with neuroinflammation and the risk of developing conditions such as AD and PD, brain injury, depression, and multiple sclerosis. However, curcumin can block PPAR-γ, which is an important mediator for the expression of these inflammatory factors. In addition, curcumin can stimulate nuclear factor erythroid-2 related factor 2 (Nrf2) and leads to improvement of inflammation, OS, cognitive functions, neuroplasticity, and memory. This activity can result in a decrease in ROS and RNS, improving mitochondrial function, and a decrease in insulin resistance, which reduces the activity of the inflammatory factors mentioned. Furthermore, it can reduce β amyloid plaque accumulation to avoid future inflammation of the nervous system. ↓: decrease; ↑: increase.

Figure 7

Summary of curcumin effects on some aging-related conditions. Curcumin possesses antioxidant and anti-inflammatory effects that are related to the prevention or treatment of memory loss, neurodegenerative diseases, sarcopenia, and frailty. These effects can play a role in mitochondrial functions that, on the other hand, are also associated with diminishing oxidative stress and inflammation. The results are associated with an increase in the synthesis of neuronal growth factors such as BDNF, NGF, and GDNF, an increase in neuroplasticity, reduction in brain neuroinflammation, and restoration of brain functions. In muscles, there is an increase in protein synthesis and a reduction in its degradation. AChE: acetylcholine esterase; AP-1: activator protein-1; BACE1: β-secretase 1; BDNF: brain-derived neurotrophic factor; COX: cyclooxygenase; ERK: extracellular signal-regulated kinase; GDNF: glial cell-derived neurotrophic factor; JNK: c-Jun N-terminal kinase; NGF: nerve growth factor; NF-κB nuclear factor kappa beta; p38MAPK: p38 mitogen-activated protein kinase; PPAR-γ: peroxisome proliferator-activated receptor gamma.