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Evolutionary Genetic Bases of Longevity and Senescence

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Longevity Genes

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 847))

Abstract

Senescence, as a time-dependent developmental process, affects all organisms at every stage in their development and growth. During this process, genetic, epigenetic and environmental factors are known to introduce a wide range of variation for longevity among individuals. As an important life-history trait, longevity shows ontogenetic relationships with other complex traits, and hence may be viewed as a composite trait. Factors that influence the origin and maintenance of diversity of life are ultimately governed by Darwinian processes. Here we review evolutionary genetic mechanisms underlying longevity and senescence in humans from a life-history and genotype-epigenetic-phenotype (G-E-P) map prospective. We suggest that synergistic and cascading effects of cis-ruptive mechanisms in the genome, and epigenetic disruptive processes in relation to environmental factors may lead to sequential slippage in the G-E-P space. These mechanisms accompany age, stage and individual specific senescent processes, influenced by positive pleiotropy of certain genes, superior genome integrity, negative-frequency dependent selection and other factors that universally regulate rarity in nature. Finally we interpret life span as an inherent property of self-organizing systems that, accordingly, maintain species-specific limits for the entire complex of fitness traits. We conclude that Darwinian approaches provide unique opportunities to discover the biological bases of longevity as well as devise individual specific medical or other interventions toward improving health span.

“Some few grow old, most suffer and fall sick,

But all must die.”

- Edwin Arnold (1906)

“So Nature deals with us and takes away

Our playthings one by one…”

- H. W. Longfellow (2004)

“Deaths from old age are due to the breakdown of one organ or another…” - J. B. S. Haldane (1949)

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Notes

  1. 1.

    White and black swans are different species; hence occupy distinct ecological niches in Northern Europe and Southern Australia, respectively. For this reason, black swans are rare in Europe, so are the white ones in Australia. Rarity of black swans in the sixteenth century England was associated with the adage “rare as a black swan.” This expression was extended by Taleb [231] to explain the occurrence of rare and unpredictable events primarily in social contexts.

  2. 2.

    The term “dragon” represents “the mythical animal that belongs to a different animal kingdom beyond the normal, with extraordinary characteristics. The term “king” … emphasize(s) the importance of those events, which are beyond the Parteo law distribution of wealth of their subjects.” Sornette and Ouillion [224].

  3. 3.

    Pareto Law, popularly known as “80–20 rule” suggests that in any self-organized systems, 80 % of effects emanate from about 20 % causes [12]Evolution is indeed a prime example of self-organizing system [123, 264]. Extending Wright’s principle of causality [261, 263, 265] which provided a basis for developing the concept of heritability [101], it may be suggested that low heritability (around 30 %) associated with life history traits, including longevity, among diverse species [198], could be explained through the universal self-organizing principle that spans across the entire tree of life [12, 123].

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Acknowledgements

I am grateful to Drs. Gil Atzmon for inspiring me to write this chapter, Nir Barzilai for the enduring encouragement, and Konstantin Khrapko for logistical support. My special thanks are due also to Dr. Sri Raj, for insightful comments. I express my profound gratitude to my family for their enduring patience and moral support.

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    Diddahally R. Govindaraju

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    Gil Atzmon, PhD

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Govindaraju, D. (2015). Evolutionary Genetic Bases of Longevity and Senescence. In: Atzmon, PhD, G. (eds) Longevity Genes. Advances in Experimental Medicine and Biology, vol 847. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2404-2_1

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