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Review
. 2019 Mar 21;177(1):200-220.
doi: 10.1016/j.cell.2019.02.038.

The Genetics of Aging: A Vertebrate Perspective

Param Priya Singh  1 , Brittany A Demmitt  1 , Ravi D Nath  1 , Anne Brunet  2
Affiliations
Review

The Genetics of Aging: A Vertebrate Perspective

Param Priya Singh et al. Cell. .

Abstract

Aging negatively impacts vitality and health. Many genetic pathways that regulate aging were discovered in invertebrates. However, the genetics of aging is more complex in vertebrates because of their specialized systems. This Review discusses advances in the genetic regulation of aging in vertebrates from work in mice, humans, and organisms with exceptional lifespans. We highlight challenges for the future, including sex-dependent differences in lifespan and the interplay between genes and environment. We also discuss how the identification of reliable biomarkers of age and development of new vertebrate models can be leveraged for personalized interventions to counter aging and age-related diseases.

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Figures

Figure 1.
Figure 1.. The Aging Clock Is Regulated by Interconnected Hallmarks
The aging clock is governed by interconnected hallmarks of aging and environmental signals (e.g., diet and exercise). The mechanical analogy illustrates the possibility that perturbations in one hallmark could affect all others. Hallmarks with vertebrate-specific components are highlighted by bold outlines. Based on López-Otín et al. (2013).
Figure 2.
Figure 2.. The Growth Hormone IGF1 Nutrient-Sensing Axis in Aging and Longevity
Genes and signaling pathways acting in nutrient sensing. The genes associated with longevity across different vertebrate species are highlighted by stars on the right. Note that mTOR also receives input from amino acids and that mTOR and FOXO also regulate other processes such as anabolic and catabolic metabolism that could affect aging and longevity.
Figure 3.
Figure 3.. Lessons in Large Lifespan Differences from Nature’s Evolutionary Experiments
Adaptations linked to evolution of longevity (and a short, compressed lifespan) are complex and involve multiple hallmarks of aging targeted by multiple evolutionary mechanisms.
Figure 4.
Figure 4.. The African Killifish: A Powerful Organism to Study Vertebrate Aging
The short-lived and genetically tractable African turquoise killifish has the power of invertebrate model systems with numerous progeny, affordable husbandry, short lifespan, rapid sexual maturity, and efficient genome editing. At the same time, it has the translational prospective of vertebrate models with an adaptive immune system, a vertebrate brain, vertebrate stem cell niches, and bones.
Figure 5.
Figure 5.. Personalized-Medicine Approaches to Delay Aging and Aging-Related Diseases
Personalized-medicine approaches to delay aging and aging-related diseases will need to integrate information about an individual’s genome and its specific variants in one or more hallmarks of aging (represented by stripes), interaction with the environment, sex, and possibly co-morbidity with diseases. These approaches will also need to account for the inherent stochasticity of aging.
See this image and copyright information in PMC

References

    1. Albani D, Ateri E, Mazzuco S, Ghilardi A, Rodilossi S, Biella G, Ongaro F, Antuono P, Boldrini P, Di Giorgi E, et al. (2014). Modulation of human longevity by SIRT3 single nucleotide polymorphisms in the prospective study “Treviso Longeva (TRELONG)”. Age (Dordr.) 36, 469–478. - PMC - PubMed
    1. Altschul DM, Hopkins WD, Herrelko ES, Inoue-Murayama M, Matsuzawa T, King JE, Ross SR, and Weiss A (2018). Personality links with lifespan in chimpanzees. eLife 7, e33781. - PMC - PubMed
    1. Arif A, Terenzi F, Potdar AA, Jia J, Sacks J, China A, Halawani D, Vasu K, Li X, Brown JM, et al. (2017). EPRS is a critical mTORC1-S6K1 effector that influences adiposity in mice. Nature 542, 357–361. - PMC - PubMed
    1. Austad SN, and Fischer KE (2016). Sex differences in lifespan. Cell Metab. 23, 1022–1033. - PMC - PubMed
    1. Aw D, Silva AB, and Palmer DB (2007). Immunosenescence: emerging challenges for an ageing population. Immunology 120, 435–446. - PMC - PubMed

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