Hallmarks of aging

Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death.

The following three premises for the interconnected hallmarks have been proposed:[2] Over time, almost all living organisms experience a gradual and irreversible increase in senescence and an associated loss of proper function of the bodily systems.

[citation needed] After a decade, the authors of the heavily cited original paper updated the set of proposed hallmarks in January 2023.

The last criterion is not present in many of the hallmarks, as science has not yet found feasible ways to amend these problems in living organisms.

Abnormal chemical structures in the DNA are formed mainly through oxidative stress and environmental factors.

[9] Telomeres are regions of repetitive nucleotide sequences associated with specialized proteins at the ends of linear chromosomes.

[12] Telomerase deficiency in humans has been linked to several aging-related diseases related to loss of regenerative capacity of tissues.

[14] The shelterin protein complex regulates telomerase activity in addition to protecting telomeres from DNA repair in eukaryotes.

[16] As an example, sirtuins are a type of protein deacetylases that promote the binding of DNA onto histones and thus turn unnecessary genes off.

With aging, the level of NAD in cells decreases and so does the ability of sirtuins to turn off unneeded genes at the right time.

[18][19] Proteostasis is the homeostatic process of maintaining all the proteins necessary for the functioning of the cell in their proper shape, structure and abundance.

[27] It has been found that forcibly overactivating these pathways in grown mice leads to accelerated aging and increased incidence of cancer.

[33] Dysfunctional mitochondria contribute to aging through interfering with intracellular signaling[34][35] and triggering inflammatory reactions.

[44] Different tissues and the cells they consist of need to orchestrate their work in a tightly controlled manner so that the organism as a whole can function.

One of the most prominent changes in cell signaling biomarkers is "inflammaging", the development of a chronic low-grade inflammation throughout the body with advanced age.

The constant presence of inflammation markers throughout the body wears out the immune system and damages healthy tissue.