Table 1.

Possible mechanisms of general aging

Risk Factors	Possible mechanisms	References
Genomic alterations	Genetic errors accumulate over time which ultimately leads to cellular apoptosis/senescence, limited stem cell renewal, and altered cytokine secretion.	12–15
Telomere shortening	Progressive telomere shortening occurs with cellular division which leads to decreased cellular proliferation, function, and possibly lifespan.	16–20
Altered epigenetic modification	Epigenetic modifications alter gene expression and cellular function in an age-dependent manner and alter cellular function over time.	21–26
Loss of proteostasis	Protein misfolding and decreased activity of proteolytic and autophagy systems leads to an accumulation of dysfunctional proteins altering cellular metabolism.	27–33
Deregulated nutrient sensing	Caloric restriction increases lifespan via activation of nutrient “sensing” molecules like sirtuins and modify the Insulin/IGF-1/mTor signaling pathway.	34–42
Mitochondrial dysfunction and ROS	Mitochondrial dysfunction increases reactive oxygen species that damage nucleic acids and oxidize fatty acids/proteins leading to genetic alterations and cellular dysfunction.	43–46
Cellular senescence	Aged cells no longer replicate and adopt a “senesence-associated secretory phenotype” that promotes inflammation and aging.	47–54
Stem cell exhaustion	Stem cell levels decrease with age, reducing the repair and regenerative capacity of tissues over the lifespan.	55–57
Inflammation and altered intercellular communication	Changes in cellular communication and inflammatory mediators lead to tissue dysfunction via multiple pathways including DNA damage, ROS, protein dysfunction, and altered autophagy.	58–61
Abnormal crosslinking	Abnormal intra- and inter-molecular bonding leads to altered transcription, translation and tissue properties.	62–66