Mitotic Dysfunction Associated with Aging Hallmarks

Abstract

Aging is a biological process characterized by the progressive deterioration of physiological functions known to be the main risk factor for chronic diseases and declining health. There has been an emerging connection between aging and aneuploidy, an aberrant number of chromosomes, even though the molecular mechanisms behind age-associated aneuploidy remain largely unknown. In recent years, several genetic pathways and biochemical processes controlling the rate of aging have been identified and proposed as aging hallmarks. Primary hallmarks that cause the accumulation of cellular damage include genomic instability, telomere attrition, epigenetic alterations and loss of proteostasis (López-Otín et al., Cell 153:1194-1217, 2013). Here we review the provocative link between these aging hallmarks and the loss of chromosome segregation fidelity during cell division, which could support the correlation between aging and aneuploidy seen over the past decades. Secondly, we review the systemic impacts of aneuploidy in cell physiology and emphasize how these include some of the primary hallmarks of aging. Based on the evidence, we propose a mutual causality between aging and aneuploidy, and suggest modulation of mitotic fidelity as a potential means to ameliorate healthy lifespan.

The increase of interfollicular epidermal stem cells and regulation of aryl hydrocarbon receptor and its repressors in the skin through hydroporation with anti‐aging cocktail

“…Although the exact mechanism of aging has not yet been fully established, it is widely accepted that senescent changes in the stem cells are responsible. 16 Our results demonstrated that hydroporation with anti-aging cocktail can recover the stem cell potential and rejuvenate old skin. We think this effect is through the enhancement of dermal microenvironment since extracellular matrix protein, such as procollagen I, fibrillin, type IV collagen, and integrin α6 were increased after treatment.…”

“…A characteristic feature of skin aging is a decrease in the capacity for wound repair and regeneration. Although the exact mechanism of aging has not yet been fully established, it is widely accepted that senescent changes in the stem cells are responsible . Our results demonstrated that hydroporation with anti‐aging cocktail can recover the stem cell potential and rejuvenate old skin.…”

The Aging‐related Approach to Detection of Mitotic Factor in Thoracic Duct Lymph of Rabbits

“…It is proposed that there is a mutual causality between aging and aneuploidy, and it suggests modulation of mitotic fidelity as a potential means to ameliorate healthy lifespan. [1] Univariate Cox regression analyses showed that a large tumor, undergoing esophagectomy, and a high mitotic rate were associated with poor survival or recurrence control. [2] A colossal amount of basic research over the past few decades has provided unprecedented insights into the highly complex process of cell division.…”

The Impact of Aging on Mechanisms of Mammalian Epimorphic Regeneration

“…Age-associated low-grade chronic inflammation, called inflammaging, correlates with increased morbidity, and mortality [1]. Given the importance of macrophage regulation in the regenerative response, inflammaging might be an important factor to consider when developing strategies for inducing regeneration in the elderly patient.…”

“…One of the most striking symptoms of aging is a dwindling ability to repair and regenerate [1]. Starting from a general peak function at sexual maturity, all tissues deteriorate at various paces until a disability threshold is reached.…”