Aging-Related Disorders and Mitochondrial Dysfunction: A Critical Review for Prospect Mitoprotective Strategies Based on Mitochondrial Nutrient Mixtures

Abstract

A number of aging-related disorders (ARD) have been related to oxidative stress (OS) and mitochondrial dysfunction (MDF) in a well-established body of literature. Most studies focused on cardiovascular disorders (CVD), type 2 diabetes (T2D), and neurodegenerative disorders. Counteracting OS and MDF has been envisaged to improve the clinical management of ARD, and major roles have been assigned to three mitochondrial cofactors, also termed mitochondrial nutrients (MNs), i.e., α-lipoic acid (ALA), Coenzyme Q10 (CoQ10), and carnitine (CARN). These cofactors exert essential–and distinct—roles in mitochondrial machineries, along with strong antioxidant properties. Clinical trials have mostly relied on the use of only one MN to ARD-affected patients as, e.g., in the case of CoQ10 in CVD, or of ALA in T2D, possibly with the addition of other antioxidants. Only a few clinical and pre-clinical studies reported on the administration of two MNs, with beneficial outcomes, while no available studies reported on the combined administration of three MNs. Based on the literature also from pre-clinical studies, the present review is to recommend the design of clinical trials based on combinations of the three MNs.

Effects and Mechanisms of Resveratrol on Aging and Age‐Related Diseases

“…Oxidative Medicine and Cellular Longevity decreased mitochondrial content are hallmarks of aging and play an important role in promoting aging [92,93]. Increasing literature reported that resveratrol regulated the mitochondrial function, thus delaying the aging process.…”

Evaluation of Dissolution Profiles of a Newly Developed Solid Oral Immediate-Release Formula Containing Alpha-Lipoic Acid

“…It is an essential cofactor in the mitochondrial aerobic metabolism and multienzyme complexes, being implied in the glucose conversion and energy production [8] and a potent antioxidant [9][10][11]. ALA displaying an excellent scavenging activity against the hydroxyl radical (HO•), with anti-inflammatory activity-by decreasing the tumor necrosis factor (TNF)-α, interleukin (IL)-1 beta (IL-1β), and IL-6 [12,13], performing an anti-aging activity [14] metal-chelating capacities and acting on the second messenger nuclear factor κB without any side effects [15]; almost meets all standards of a perfect anti-aging substance [15]. Consequently, the widespread use of ALA as a functional compound is increasing [16].…”

Mitochondrial Functioning and the Relations among Health, Cognition, and Aging: Where Cell Biology Meets Cognitive Science

“…In other words, performance on measures of executive attention and the cognitive-composite might then provide highly sensitive behavioral measures of cognitive aging and cognitive deficits associated with disorders that involve mitochondrial dysfunctions, such as those associated with disruptions to glucose homeostasis ( Section 3.1 ). These behavioral measures might also prove to be useful for the assessment of the efficacy of pharmacological treatments of mitochondrial disorders as a means to address age-related or disease-related cognitive decline [ 143 ].…”