Stem cells lose their ability to divide as we age, and we are unable to replace cells that have migrated, differentiated, or died. As a result, we show outward symptoms of aging, such as gray hair.
As cells age, their mitochondria start to lose their integrity due to the build-up of oxidative stress. Compromised mitochondrial function leads to a number of adverse events, such as increased apoptosis induction, that correlate with aging.
Shortened telomeres are associated with aging cells that are senescent. As cells divide, the telomere ends of chromosomes get shorter. Eventually, telomerase gets silenced and the telomeres are too short for cells to divide.
As cells are exposed to environmental factors, they are subject to changes in their genome through epigenetic mechanisms. Such changes accumulate over time and have been correlated with the decline observed in aging cells.
As cells age, they show an increase in self-preserving signals that result in damage elsewhere. Impaired intercellular communication with aging contributes to decline in tissue health.
As cells age, environmental stresses add up and mechanisms responsible for maintaining proper protein composition start to decline. Proteins lose their stability, autophagic processes start to fail, and misfolded proteins accumulate.
Autophagy is an essential process of removing cellular waste products. It is a component of proteostasis, although now a hallmark in its own right since loss of effective autophagy is a key contributor to the decline of organelle turnover and an accelerator of aging.
Microbes living in and on us are now widely understood to be intricately connected to health and disease. In part due to the gradual decline of our immune system’s effectiveness, and since one of our immune system’s roles is in shaping the diversity and species members of our microbiome, our aging microbiomes gradually lose diversity and become altered in their composition.
“Inflammaging” is a term coined to describe the gradual increase of inflammation as we age. It has wide-ranging implications in disease-related activity such as arteriosclerosis, neuroinflammation, osteoarthritis and bone degradation. Inflammation is also clearly linked to all other hallmarks of aging both in its tendency to promote and result from other hallmarks.
