Considering the Non-Genomic Hallmarks of Aging

The Hallmarks of Aging were first published some years ago now, long enough to be expanded upon and much debated. The hallmarks are a list of characteristic changes in cell and tissue biochemistry noted to take place with advancing age, some of which are likely causes of age-related degeneration, some of which are likely downstream consequences, and all of which interact with one another. As often happens in such matters, the original hallmarks of aging drew from, and then eclipsed in terms of attention, the much earlier Strategies for Engineered Negligible Senescence (SENS) list of forms of cell and tissue damage that are causative of aging. In this review paper, researchers provide an overview of the subset of the hallmarks of aging that are not directly connected to the genome.

Aging is defined as a process in which there is a gradual loss of organ function and a reduction in the ability to regenerate. This is due to the multiple changes that occur at the molecular and cellular levels. Various theories have been formulated to explain the cause of aging, e.g., oxidative damage or programmed theory. These theories cover only a certain aspect of the aging process and do not consider its full complexity. The theory that connects all causes of aging is based on the hallmarks of aging, molecular processes that accumulate damage during aging that exceed the cell's ability to repair it.

The most significant changes at the genomic level (DNA damage, telomere shortening, epigenetic changes) and non-genomic changes are referred to as hallmarks of aging. The hallmarks of aging and cancer are intertwined. Many studies have focused on genomic hallmarks, but non-genomic hallmarks are also important and may additionally cause genomic damage and increase the expression of genomic hallmarks. Understanding the non-genomic hallmarks of aging and cancer, and how they are intertwined, may lead to the development of approaches that could influence these hallmarks and thus function not only to slow aging but also to prevent cancer. In this review, we focus on non-genomic changes. We discuss cell senescence, disruption of proteostasis, deregualation of nutrient sensing, dysregulation of immune system function, intercellular communication, mitochondrial dysfunction, stem cell exhaustion, and dysbiosis.