Hallmarks of Aging

Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. The hallmarks of aging are the types of biochemical changes that occur in all organisms that experience biological aging and lead to a progressive loss of physiological integrity, impaired function and, eventually, death. They were first listed in a landmark paper in 2013^[1] to conceptualize the essence of biological aging and its underlying mechanisms.

Criteria

Each hallmark was chosen to try to fulfill the following criteria:^[1]

manifests during normal aging;
experimentally increasing it accelerates aging;
experimentally amending it slows the normal aging process and increases healthy lifespan.

These conditions are met to different extents by each of these hallmarks. 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.

History

2013 The scientific journal Cell published the article "The Hallmarks of Aging", that was translated to several languages and determined the directions of many studies.^[1]
2022 It was proposed to expand the list of the nine hallmarks of aging with five more.^[2]^[3]^[4]
2023 In a paywalled review, the authors of a heavily cited paper on the hallmarks of aging update the set of proposed hallmarks after a decade.^[5]^[6] A review with overlapping authors merge or link various hallmarks of cancer with those of aging.^[7]

Todo

2013, The hallmarks of aging ^[1]
2023, Chronic inflammation and the hallmarks of aging ^[8]

References

↑ ^1.0 ^1.1 ^1.2 ^1.3 López-Otín C et al.: The hallmarks of aging. Cell 2013. (PMID 23746838) [PubMed] [DOI] [Full text] Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. This deterioration is the primary risk factor for major human pathologies, including cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases. Aging research has experienced an unprecedented advance over recent years, particularly with the discovery that the rate of aging is controlled, at least to some extent, by genetic pathways and biochemical processes conserved in evolution. This Review enumerates nine tentative hallmarks that represent common denominators of aging in different organisms, with special emphasis on mammalian aging. These hallmarks are: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. A major challenge is to dissect the interconnectedness between the candidate hallmarks and their relative contributions to aging, with the final goal of identifying pharmaceutical targets to improve human health during aging, with minimal side effects.
↑ Schmauck-Medina T, Molière A, Lautrup S, Zhang J, Chlopicki S, Madsen HB, Cao S, Soendenbroe C, Mansell E, Vestergaard MB, Li Z, Shiloh Y, Opresko PL, Egly JM, Kirkwood T, Verdin E, Bohr VA, Cox LS, Stevnsner T, Rasmussen LJ, Fang EF; "New hallmarks of ageing: a 2022 Copenhagen ageing meeting summary" , https://doi.org/10.18632/aging.204248
↑ Researchers Propose Five New Hallmarks of Aging, https://www.lifespan.io/news/researchers-propose-five-new-hallmarks-of-aging/
↑ Arguing for an Expansion of the Hallmarks of Aging, https://www.fightaging.org/archives/2022/09/arguing-for-an-expansion-of-the-hallmarks-of-aging/
↑ Template:cite news
↑ López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G; "Hallmarks of aging: An expanding universe" , https://www.cell.com/cell/fulltext/S0092-8674(22)01377-0 , https://doi.org/10.1016/j.cell.2022.11.001
↑ López-Otín C, Pietrocola F, Roiz-Valle D, Galluzzi L, Kroemer G; "Meta-hallmarks of aging and cancer" , https://www.cell.com/cell-metabolism/fulltext/S1550-4131(22)00492-2 , https://doi.org/10.1016/j.cmet.2022.11.001
↑ Baechle JJ et al.: Chronic inflammation and the hallmarks of aging. Mol Metab 2023. (PMID 37329949) [PubMed] [DOI] [Full text] BACKGROUND: Recently, the hallmarks of aging were updated to include dysbiosis, disabled macroautophagy, and chronic inflammation. In particular, the low-grade chronic inflammation during aging, without overt infection, is defined as "inflammaging," which is associated with increased morbidity and mortality in the aging population. Emerging evidence suggests a bidirectional and cyclical relationship between chronic inflammation and the development of age-related conditions, such as cardiovascular diseases, neurodegeneration, cancer, and frailty. How the crosstalk between chronic inflammation and other hallmarks of aging underlies biological mechanisms of aging and age-related disease is thus of particular interest to the current geroscience research. SCOPE OF REVIEW: This review integrates the cellular and molecular mechanisms of age-associated chronic inflammation with the other eleven hallmarks of aging. Extra discussion is dedicated to the hallmark of "altered nutrient sensing," given the scope of Molecular Metabolism. The deregulation of hallmark processes during aging disrupts the delicate balance between pro-inflammatory and anti-inflammatory signaling, leading to a persistent inflammatory state. The resultant chronic inflammation, in turn, further aggravates the dysfunction of each hallmark, thereby driving the progression of aging and age-related diseases. MAIN CONCLUSIONS: The crosstalk between chronic inflammation and other hallmarks of aging results in a vicious cycle that exacerbates the decline in cellular functions and promotes aging. Understanding this complex interplay will provide new insights into the mechanisms of aging and the development of potential anti-aging interventions. Given their interconnectedness and ability to accentuate the primary elements of aging, drivers of chronic inflammation may be an ideal target with high translational potential to address the pathological conditions associated with aging.

[pmid23746838-1] 1.0 ^1.1 ^1.2 ^1.3 López-Otín C et al.: The hallmarks of aging. Cell 2013. (PMID 23746838) [PubMed] [DOI] [Full text] Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. This deterioration is the primary risk factor for major human pathologies, including cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases. Aging research has experienced an unprecedented advance over recent years, particularly with the discovery that the rate of aging is controlled, at least to some extent, by genetic pathways and biochemical processes conserved in evolution. This Review enumerates nine tentative hallmarks that represent common denominators of aging in different organisms, with special emphasis on mammalian aging. These hallmarks are: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. A major challenge is to dissect the interconnectedness between the candidate hallmarks and their relative contributions to aging, with the final goal of identifying pharmaceutical targets to improve human health during aging, with minimal side effects.

[2] Schmauck-Medina T, Molière A, Lautrup S, Zhang J, Chlopicki S, Madsen HB, Cao S, Soendenbroe C, Mansell E, Vestergaard MB, Li Z, Shiloh Y, Opresko PL, Egly JM, Kirkwood T, Verdin E, Bohr VA, Cox LS, Stevnsner T, Rasmussen LJ, Fang EF; "New hallmarks of ageing: a 2022 Copenhagen ageing meeting summary" , https://doi.org/10.18632/aging.204248

[3] Researchers Propose Five New Hallmarks of Aging, https://www.lifespan.io/news/researchers-propose-five-new-hallmarks-of-aging/

[4] Arguing for an Expansion of the Hallmarks of Aging, https://www.fightaging.org/archives/2022/09/arguing-for-an-expansion-of-the-hallmarks-of-aging/

[5] Template:cite news

[6] López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G; "Hallmarks of aging: An expanding universe" , https://www.cell.com/cell/fulltext/S0092-8674(22)01377-0 , https://doi.org/10.1016/j.cell.2022.11.001

[7] López-Otín C, Pietrocola F, Roiz-Valle D, Galluzzi L, Kroemer G; "Meta-hallmarks of aging and cancer" , https://www.cell.com/cell-metabolism/fulltext/S1550-4131(22)00492-2 , https://doi.org/10.1016/j.cmet.2022.11.001

[pmid37329949-8] Baechle JJ et al.: Chronic inflammation and the hallmarks of aging. Mol Metab 2023. (PMID 37329949) [PubMed] [DOI] [Full text] BACKGROUND: Recently, the hallmarks of aging were updated to include dysbiosis, disabled macroautophagy, and chronic inflammation. In particular, the low-grade chronic inflammation during aging, without overt infection, is defined as "inflammaging," which is associated with increased morbidity and mortality in the aging population. Emerging evidence suggests a bidirectional and cyclical relationship between chronic inflammation and the development of age-related conditions, such as cardiovascular diseases, neurodegeneration, cancer, and frailty. How the crosstalk between chronic inflammation and other hallmarks of aging underlies biological mechanisms of aging and age-related disease is thus of particular interest to the current geroscience research. SCOPE OF REVIEW: This review integrates the cellular and molecular mechanisms of age-associated chronic inflammation with the other eleven hallmarks of aging. Extra discussion is dedicated to the hallmark of "altered nutrient sensing," given the scope of Molecular Metabolism. The deregulation of hallmark processes during aging disrupts the delicate balance between pro-inflammatory and anti-inflammatory signaling, leading to a persistent inflammatory state. The resultant chronic inflammation, in turn, further aggravates the dysfunction of each hallmark, thereby driving the progression of aging and age-related diseases. MAIN CONCLUSIONS: The crosstalk between chronic inflammation and other hallmarks of aging results in a vicious cycle that exacerbates the decline in cellular functions and promotes aging. Understanding this complex interplay will provide new insights into the mechanisms of aging and the development of potential anti-aging interventions. Given their interconnectedness and ability to accentuate the primary elements of aging, drivers of chronic inflammation may be an ideal target with high translational potential to address the pathological conditions associated with aging.

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