Antiaging effects of bioactive molecules isolated from plants and fungi

Abstract

Aging is influenced by many lifestyle choices that are under human control, including nutrition and exercise. The most effective known antiaging intervention consists of calorie restriction (CR), which increases lifespan in yeasts, worms, fruit flies, mice, and nonhuman primates. CR also improves healthspan by preventing the development of various aging‐related diseases such as cancer, cardiovascular disease, diabetes, and neurodegeneration. Many compounds isolated from plants and fungi prolong lifespan and prevent age‐related diseases in model organisms. These plant and fungal compounds modulate the same cellular and physiological pathways as CR, including those involving insulin and insulin‐like growth factor‐1, mammalian target of rapamycin, and sirtuins. Modulation of these aging‐related pathways results in the activation of various cellular processes such as autophagy, DNA repair, and neutralization of reactive oxygen species. Together, these cellular processes are believed to delay aging and prevent chronic diseases by improving bodily functions and stress resistance. We review here the mechanisms of action of plant and fungal molecules possessing antiaging properties and discuss the possibilities and challenges associated with the development of antiaging compounds isolated from natural products.

Emerging use of senolytics and senomorphics against aging and chronic diseases

“…Bcl, B-cell lymphoma; HSP90, heat-shock protein 90; IKK, inhibitor of nuclear factor kappa B kinase; IκBα, inhibitor of nuclear factor kappa B kinase subunit alpha; IL-1R, interleukin-1 receptor; IL-6R, interleukin-6 receptor; JAK, Janus kinase; MAPK, mitogen-activated protein kinase; NF-κB, nuclear factor kappa-light-chain enhancer of activated B cells; PI3K, phosphoinositide 3-kinase; RB, retinoblastoma protein; ROS, reactive oxygen species; STAT, signal transducer and activator of transcription Many phytochemicals have been screened for their ability to inhibit senescence. 41 In a panel of 10 polyphenols examined, fisetin [7] was the most potent senolytic in cultured senescent murine and human fibroblasts; luteolin [8] and curcumin [9] produced weak effects in these experiments. When tested in aged wild-type mice, fisetin reduced senescent cell accumulation in various tissues as well as pathological scores in the brain and liver.…”

“…59,60 While a high level of stress is detrimental to cells and organs, mild stress may be beneficial by activating cellular defense mechanisms, such as autophagy, mitochondrial biogenesis, DNA repair, and expression of antioxidant and detoxifying enzymes. [6][7][8]61,62 By inducing these cellular protective mechanisms, senomorphic compounds may lower the level of cellular stress, therefore preventing cells from entering senescence or apoptosis. [6][7][8][61][62][63][64] Stress intensity may determine whether cells become senescent or apoptotic.…”

“…[6][7][8]61,62 By inducing these cellular protective mechanisms, senomorphic compounds may lower the level of cellular stress, therefore preventing cells from entering senescence or apoptosis. [6][7][8][61][62][63][64] Stress intensity may determine whether cells become senescent or apoptotic. A low amount of DNA damage may induce p21-mediated cell cycle arrest, allowing cells to repair DNA damage before re-entering the cell cycle.…”

“…Many compounds found in plants and fungi inhibit mTOR activity, including caffeine [32], polyphenols, epicatechin [33], berberine [34], capsaicin [35], genistein [36] and curcumin. 7,8 Recent studies suggest that cellular senescence may be reversible under some conditions. For instance, resveratrol analogs reduce the senescence markers p16 INK4/6 and SA-β-Gal by altering splicing factor expression in senescent fibroblasts.…”

Nanodelivery of Natural Antioxidants: An Anti-aging Perspective

“…Due to such properties, they are considered to be promising candidates for developing healthspan-and lifespan-promoting interventions (Leonov et al, 2015). The efficiency of phytochemicals such as resveratrol, curcumin, catechins, genistein, and quercetin in counteracting various pathological conditions mediated by aging-related oxidative stress and associated chronic inflammation has been repeatedly reported (Corrêa et al, 2018;Martel et al, 2019). Chemical structures of the most commonly used phytotherapeutic compounds with potent antioxidant properties are presented in Figure 2 below.…”