An Updated Overview on the Role of Small Molecules and Natural Compounds in the “Young Science” of Rejuvenation

Abstract

Aging is a gradual process that occurs over time which leads to a progressive decline of cells and tissues. Telomere shortening, genetic instability, epigenetic alteration, and the accumulation of misfolded proteins represent the main hallmarks that cause perturbed cellular functions; this occurs in conjunction with the progression of the so-called “aging clocks”. Rejuvenation aims to influence the natural evolution of such aging clocks and to enhance regenerative capacity, thus overcoming the limitations of common anti-aging interventions. Current rejuvenation processes are based on heterochronic parabiosis, cell damage dilution through asymmetrical cell division, the excretion of extracellular vesicles, the modulation of genetic instability involving G-quadruplexes and DNA methylation, and cell reprogramming using Yamanaka factors and the actions of antioxidant species. In this context, we reviewed the most recent contributions that report on small molecules acting as senotherapeutics; these molecules act by promoting one or more of the abovementioned processes. Candidate drugs and natural compounds that are being studied as potential rejuvenation therapies act by interfering with CDGSH iron-sulfur domain 2 (CISD2) expression, G-quadruplex structures, DNA methylation, and mitochondrial decay. Moreover, direct and indirect antioxidants have been reported to counteract or revert aging through a combination of mixed mechanisms.

Researching New Drug Combinations with Senolytic Activity Using Senescent Human Lung Fibroblasts MRC-5 Cell Line

“…Senomorphic drugs suppress the expression of senescence markers and alter the release of cytokines, chemokines, and growth factors associated with SASP without inducing the apoptosis of senescent cells. The senomorphics described so far include inhibitors of IkB kinase (IKK) and nuclear factor (NF)-kB [ 19 ], inhibitors of the Janus kinase (JAK) pathway [ 20 ], and antioxidant substances, such as polyphenols from natural sources [ 21 ]. Some compounds, such as fisetin, a natural polyphenol, have shown senomorphic effects in vitro on some cells while showing senolytic activity on other cell types [ 22 ].…”

Hesperetin activates CISD2 to attenuate senescence in human keratinocytes from an older person and rejuvenates naturally aged skin in mice

“…Notably, previous studies have revealed that hesperetin, a flavanone aglycone found in citrus fruit peel, exerts several beneficial properties; these include acting as an anti-oxidant agent and as anti-inflammation agent, as well as providing cell protection. All of the above promote skin health [ 11 ]. In human dermal fibroblast cells, hesperetin alleviates UVA-induced damage, including suppressing cell death, reducing oxidative stress, and decreasing the expression of matrix metalloproteinases (MMPs) and pro-inflammatory cytokines [ 12 ].…”

Comparing the Effects of Different Injection Techniques Used in Lip Augmentation on Filler Migration and Patient Satisfaction

“…Fillers are used for volume replacement and enhancement procedures. These substances are not autologous but synthetic and they can reduce wrinkles, correct dermal depressions, and scars caused by trauma, enhance facial contours, and moisturize the skin [ 4 ].…”