Comparative genetics of longevity and cancer: insights from long-lived rodents

Gorbunova, Vera; Seluanov, Andrei; Zhang, Zhengdong; Gladyshev, Vadim N.; Vijg, Jan

doi:10.1038/nrg3728

Cited by 183 publications

(175 citation statements)

References 79 publications

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“…This should not be surprising as a decrease in stem cell functionality is an integrative hallmark of aging (Lopez‐Otin, Blasco, Partridge, Serrano & Kroemer, 2013), while the maintenance of it is a cornerstone of naturally evolved mechanisms of fighting aging. Different invertebrate and vertebrate long‐lived species developed independent strategies for repressing aging, but often their life trajectory is related to cell cycle control, telomere and genome maintenance, and tumor suppression (Gorbunova, Seluanov, Zhang, Gladyshev & Vijg, 2014; Ma et al., 2016). …”

Section: Discussionmentioning

confidence: 99%

Resilience to aging in the regeneration‐capable flatworm Macrostomum lignano

et al. 2018

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SummaryAnimals show a large variability of lifespan, ranging from short‐lived as Caenorhabditis elegans to immortal as Hydra. A fascinating case is flatworms, in which reversal of aging by regeneration is proposed, yet conclusive evidence for this rejuvenation‐by‐regeneration hypothesis is lacking. We tested this hypothesis by inducing regeneration in the sexual free‐living flatworm Macrostomum lignano. We studied survival, fertility, morphology, and gene expression as a function of age. Here, we report that after regeneration, genes expressed in the germline are upregulated at all ages, but no signs of rejuvenation are observed. Instead, the animal appears to be substantially longer lived than previously appreciated, and genes expressed in stem cells are upregulated with age, while germline genes are downregulated. Remarkably, several genes with known beneficial effects on lifespan when overexpressed in mice and C. elegans are naturally upregulated with age in M. lignano, suggesting that molecular mechanism for offsetting negative consequences of aging has evolved in this animal. We therefore propose that M. lignano represents a novel powerful model for molecular studies of aging attenuation, and the identified aging gene expression patterns provide a valuable resource for further exploration of anti‐aging strategies.

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Section: Discussionmentioning

confidence: 99%

Resilience to aging in the regeneration‐capable flatworm Macrostomum lignano

et al. 2018

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“…Naked mole rats, another cancerfree rodent, with an impressive 30-year lifespan, have evolved hypersensitivity to cellular contact inhabitation mediated through alternative INK4a/b splicing and very high molecular weight hyaluronan [164][165][166]. Bowhead whales, the longest living mammal with a lifespan of over 200 years and reportedly very low cancer rates, recently were described to harbour genomic alterations associated with cancer, ageing, cell cycle and DNA repair (e.g.…”

Section: Other Animals Besides Dogs (Sea Lions Whales Bats and Nakementioning

confidence: 99%

Comparative oncology: what dogs and other species can teach us about humans with cancer

Schiffman

Breen

2015

Phil. Trans. R. Soc. B

305

315

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One contribution of 18 to a theme issue 'Cancer across life: Peto's paradox and the promise of comparative oncology'. Over 1.66 million humans (approx. 500/100 000 population rate) and over 4.2 million dogs (approx. 5300/100 000 population rate) are diagnosed with cancer annually in the USA. The interdisciplinary field of comparative oncology offers a unique and strong opportunity to learn more about universal cancer risk and development through epidemiology, genetic and genomic investigations. Working across species, researchers from human and veterinary medicine can combine scientific findings to understand more quickly the origins of cancer and translate these findings to novel therapies to benefit both human and animals. This review begins with the genetic origins of canines and their advantage in cancer research. We next focus on recent findings in comparative oncology related to inherited, or genetic, risk for tumour development. We then detail the somatic, or genomic, changes within tumours and the similarities between species. The shared cancers between humans and dogs that we discuss include sarcoma (osteosarcoma, soft tissue sarcoma, histiocytic sarcoma, hemangiosarcoma), haematological malignancies (lymphoma, leukaemia), bladder cancer, intracranial neoplasms (meningioma, glioma) and melanoma. Tumour risk in other animal species is also briefly discussed. As the field of genomics advances, we predict that comparative oncology will continue to benefit both humans and the animals that live among us.

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“…It also possesses remarkably good health throughout its life. Cancer has never been observed in a naked mole rat in captivity (Gorbunova et al 2014). The reason for this cancer resistance, which presumably contributes to longevity, is an intriguing question.…”

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confidence: 99%

Cancer resistance, high molecular weight hyaluronic acid, and longevity

Fisher

2015

J. Cell Commun. Signal.

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Longevity varies greatly among mammals. The naked mole rat is among the longest-lived rodents, having an average lifespan of 32 years, compared to the similarly-sized house mouse with lifespan of 4 years. The rate of cancer also varies widely among mammals and interestingly, the naked mole rat is essentially cancer-free (Gorbunova et al., Nat Rev Genet 15(531):540, 2014). A series of elegant studies (Tian et al. Nature 499:346-349, 2013) has revealed that this cancer resistance derives from the abundant production of high molecular weight hyaluronic acid. Remarkably, high molecular weight hyaluronic acid, which accumulates within the extracellular matrix, stimulates an intracellular pathway that induces expression of p16 ink4a and suppresses oncogenic transformation.

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Comparative genetics of longevity and cancer: insights from long-lived rodents

Cited by 183 publications

References 79 publications

Resilience to aging in the regeneration‐capable flatworm Macrostomum lignano

Resilience to aging in the regeneration‐capable flatworm Macrostomum lignano

Comparative oncology: what dogs and other species can teach us about humans with cancer

Cancer resistance, high molecular weight hyaluronic acid, and longevity

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