Hallmarks of Ageing

The inevitability of aging has fascinated humanity since antiquity.Despite remarkable scientific advances, the complexity of aging continues to impede a complete understanding. In 2013, the Hallmarks of Aging were introduced to establish an organized, systematic, and integrative framework for research in this field. More than a decade later, advancements in the area prompted an updated version that incorporated three additional hallmarks while preserving the original conceptual structure. This review aims to explain the underlying biological mechanisms, highlight recent insights and emerging key players, and provide high-quality antibodies and proteins to support further research on these critical antigens.

Genome Instability &

Genome instability refers to an increased tendency for alterations in the genome, like mutations and chromosomal rearrangement. As organisms age, several cellular processes that maintain genomic integrity become impaired, including DNA damage recognition (ATM) and DNA repair pathways like homologous recombination and non-homologous end joining (ATR, BRCA1). The result is a higher burden of DNA lesions and mutations in somatic cells, which not only contributes to cellular senescence and functional decline but also increases the risk of malignant transformation. Therefore, genome instability is also a hallmark of cancer. Accumulated mutations over time can inactivate tumor suppressor genes (TP53) or activate oncogenes.

Telomere Attrition

Telomeres are repetitive nucleotide sequences (TTAGGG repeats in humans) located at the ends of linear chromosomes, serving to protect chromosomal DNA from deterioration or fusion with neighboring chromosomes. With each round of DNA replication, due to the end-replication problem, telomeres progressively shorten in somatic cells, unless compensated by telomerase activity. Critically shortened telomeres lose their protective function Telomere attrition is a cumulative process driven over time by replicative cell divisions (mitotic clock), oxidative stress prinflammatory environments

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References

1. López-Otín, Blasco, Partridge, Serrano, Kroemer: "The hallmarks of aging." in: Cell, Vol. 153, Issue 6, pp. 1194-217, (2013) (PubMed).
2. Guerville, De Souto Barreto, Ader, Andrieu, Casteilla, Dray, Fazilleau, Guyonnet, Langin, Liblau, Parini, Valet, Vergnolle, Rolland, Vellas: "Revisiting the Hallmarks of Aging to Identify Markers of Biological Age." in: The journal of prevention of Alzheimer's disease, Vol. 7, Issue 1, pp. 56-64, (2021) (PubMed).
3. López-Otín, Blasco, Partridge, Serrano, Kroemer: "Hallmarks of aging: An expanding universe." in: Cell, Vol. 186, Issue 2, pp. 243-278, (2023) (PubMed).
4. Tenchov, Sasso, Wang, Zhou: "Aging Hallmarks and Progression and Age-Related Diseases: A Landscape View of Research Advancement." in: ACS chemical neuroscience, Vol. 15, Issue 1, pp. 1-30, (2024) (PubMed).
5. Tartiere, Freije, López-Otín: "The hallmarks of aging as a conceptual framework for health and longevity research." in: Frontiers in aging, Vol. 5, pp. 1334261, (2024) (PubMed).