Anti-senescence compounds: A potential nutraceutical approach to healthy aging

Abstract

The desire of eternal youth seems to be as old as mankind. However, the increasing life expectancy experienced by populations in developed countries also involves a significantly increased incidence of the most common age-related diseases (ARDs). Senescent cells (SCs) have been identified as culprits of organismal aging. Their number rises with age and their senescence-associated secretory phenotype fuels the chronic, pro-inflammatory systemic state (inflammaging) that characterizes aging, impairing the regenerative ability of stem cells and increasing the risk of developing ARDs. A variegated class of molecules, including synthetic senolytic compounds and natural compounds contained in food, have been suggested to possess anti-senescence activity. Senolytics are attracting growing interest, and their safety and reliability as anti-senescence drugs are being assessed in human clinical trials. Notably, since SCs spread inflammation at the systemic level through pro-oxidant and pro-inflammatory signals, foods rich in polyphenols, which exert antioxidant and anti-inflammatory actions, have the potential to be harnessed as "anti-senescence foods" in a nutraceutical approach to healthier aging. We discuss the beneficial effects of polyphenol-rich foods in relation to the Mediterranean diet and the dietary habits of long-lived individuals, and examine their ability to modulate bacterial genera in the gut.

Manipulation of molecular pathways and senescence hallmarks by natural compounds in fibroblast cells

“…Furthermore, OS activates cellular inflammatory responses that are generally controlled by the transcription factor NF-κB. 11,16,60 For instance, plant polyphenols such as resveratrol, quercetin, naringenin, curcumin, epigallocatechin gallate, epicatechin, and catechin were proved to counter the increased OS and accordingly possessed antisenescence effects, 16,61,62 thereby, some of them entered to clinical trials. 48 In addition, ROS stimulate the NF-κB signaling pathway, which can be blocked by various 51 stated that the level of serum/plasma inflammatory mediator increases up to 2 to 4 times in aging organs.…”

“…9,10 Under tense conditions, for example, telomeric attrition and oncogenicor oxidative-stress, DNA is damaged, resulting in p53 activation. 16 On the basis of the available ethnobotanical knowledge, the presence of specific chemical groups, and the consideration that there is a paucity of information regarding their biological profile, four plant species were selected to examine their protective effects on senescence-associated biomarkers. In turn, p21 binds to the cyclin-dependent kinase 2 (CDK2) and prevents CDK2 from forming a complex with cyclin E and cyclin A. CDK2-cyclin E/A is found to be crucial for cell cycle progression and DNA replication to begin, whereby p21 blocks cell replication.…”

Age and Periodontal Health—Immunological View

“…Nevertheless it is very clear that across the human population there is extensive variation in aging effects that generally reflect a composite of genetics and environmental exposures [160]. This variation has engendered discussion of the concept of “biological aging” [160–165], encompassing strategies to develop anti-aging (“geroprotective”) or senolytic (kill senescent cells) therapeutics to slow the aging processes and/or enhance healthy biologic aging [166–171]. …”

The Experimental Pathology at Ancona: 50 Years of Exciting and Pioneering Research on Human Pathology

“…Since epigenetic modifications are reversible, affecting gene expression without altering the DNA sequence, recently we activated a line of research aimed to assess the impact of lifestyles, such as exercise and diet, on aging processes [2,3,34,63]. Although in vivo detection and targeting of senescent cells are still being investigated, it is likely that therapeutic strategies based on antioxidant and anti-inflammatory compounds would involve generalized anti-aging effects [59].…”