Aging is associated with many disease conditions, yet at a more basic level it affects cells’ essential functions, their normal life-and-death cycles, and their messaging within the body. Intracellular aging processes influence genomic and telomere stability, stem cell function, epigenetic patterning, cellular nutrient-sensing and metabolism, and the function of mitochondria and organelles. Biological aging also reduces cells’ fundamental capacity for performing cell renewal processes that are crucial for their performance and ability to replicate normally.
Senolytics are substances that, like the adaptive stress imposed by fasting or intense physical exertion, activate cells’ mechanisms for achieving programmed cell death. Most senolytics are drugs, but certain phytonutrients have displayed mild senolytic activity. Senomorphics encompass a broad variety of substances that modulate the function of senescent cells. Senomorphics may influence the expression of the senescence-associated secretory phenotype (SASP), help normalize the function of mitochondria or lysosome (organelles that digest and store cell waste), or improve cell redox balance, telomerase activity, or network signaling.
Senomorphic approaches bear some similarity to wellness-oriented lifestyles, and some senomorphic candidates (e.g., nutrients) may be appropriate for regular intake. Strong senolytics, on the other hand, are more akin to episodic therapies like intermittent fasting, and may prove deleterious if overused. However, weaker senolytic influences, such as certain nutrients and phytonutrients, more gently stimulate cell renewal pathways, and are more consistent with the effects of a long-term healthful diet.
This article reviews the rapidly-evolving research dealing with cellular senescence. The authors note three main strategies for ameliorating cell aging, but emphasize the need for balance among them. These strategies include:: encouraging normal cell renewal, enhancing the immune system’s ability to reduce senescent cell burden, and limiting circumstances that induce cellular biological aging and development of the SASP. They stress that imbalance among these processes may have unintended results. For example, excessive senomorphic suppression of the SASP could negatively impact immune clearance of senescent cells, and overly powerful, prolonged, or non-selective senolytic treatment could burden stem cells or impair immune cell function.
Evolving Research on Ameliorating Cell Senescence
This article details major causes of premature cellular senescence, including modifiable dietary factors. The authors provide numerous examples of nutrients and phytonutrients with biological activities that may simultaneously address multiple aspects of cell senescence and the SASP.