David Gems

David Herbert Gems
Born1960
NationalityBritish
Alma materUniversity of Sussex, University of Glasgow
Scientific career
FieldsGenetics, biogerontology
InstitutionsUniversity College London
Thesis Transformation and development of Aspergillus nidulans  (1990)
Doctoral advisorA.J. Clutterbuck

David Gems is a British geneticist who studies the biology and genetics of ageing (biogerontology). He is Professor of Biogerontology at the Research Department of Genetics, Evolution and Environment, University College London and he is a co-founder and Research Director of the UCL Institute of Healthy Ageing.[1][2] His work concerns understanding the underlying causes of aging. His research laboratory tests theories of aging and develops new ones using a short-lived animal model C. elegans.[3]

Early life and career

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Gems went to Dartington Hall School before attending the University of Sussex, graduating in 1983 with a BSc in Biochemistry.[4] After graduation in 1983, Gems pursued various work in Costa Rica, Nicaragua, Mexico and USA.[4] He then returned to the UK, obtaining a PhD in Genetics from the University of Glasgow in 1990, working the genetics of development in Aspergillus nidulans.

In 1993 he moved to the University of Missouri Columbia and the lab of Don Riddle,[5] discoverer of the gene daf-2 which controls lifespan, to work on C. elegans aging. In 1997 he set up his own research group at UCL, supported by a Royal Society University Research Fellowship. Subsequent expansion of research on aging at UCL led in 2007 to the creation of the Institute of Healthy Ageing (IHA),[6] founded by Gems and Dame Linda Partridge, its first Director, with the support of the Wellcome Trust. In 2012 he was appointed Professor of Biogerontology, and in 2019 Research Director of the IHA.

Research

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From 1993 to 2014, much of Gems's work related to long-lived C. elegans daf-2 mutants and the defects in insulin/IGF-1 signaling that controls their lifespan.[1] A key contribution concerned to whether this pathway controls aging in other animals (including humans). In collaborative work at UCL (2001-9), Gems contributed to showing that it does, in fruit flies[7] (with Linda Partridge) and in mice (with Dominic Withers).[8]

During the 2000s his work also focused on identifying the processes of aging itself that insulin/IGF-1 signaling controls, in an attempt to discover what really causes aging. The role of antioxidant defenses, and the validity of the oxidative damage theory of aging was tested in a series of studies from 2003 to 2012.[9][10][11] This contributed to the demise of the oxidative damage theory of aging, which had guided research on aging for several decades, in 2008-2009.[12]

From 2013 onwards, Gems's work explored new theories and experimental approaches for understanding aging, given what he claimed was the failure of prior research to understand C. elegans aging at the fundamental level. This included testing ideas from an emerging, new school of thought about the causes of aging, the programmatic theory[13] (also known as the hyperfunction theory, and the developmental theory). This was developed by George C. Williams,[14] Mikhail Blagosklonny,[15] João Pedro de Magalhães[16] and Dr Carina Kern.[17] Gems performed a series of studies suggesting that age-related disease in C. elegans were the result of programmatic changes, rather than molecular damage accumulation, traditionally viewed as a main cause of aging[18][19][20][21]

Gems has been an outspoken critic of what he argues are ideas that are inadequate to guide research towards an understanding of the aging process. These include the assumption that aging is caused by molecular damage,[22] the disposable soma theory,[13] the hallmarks of aging, which he branded a "pseudo-paradigm",[23] and the concept of cellular senescence, which he argued has been outgrown by recent research progress.[24]

His recent work has increasingly involved developing new theories of aging that extend the programmatic theory, including the existence of programmed adaptive death in colonial organisms, perhaps including C. elegans;[25] the possibility that C. elegans exhibit reproductive suicide as seen in semelparous organisms such as Pacific salmon;[26][27] and a multifactorial model, based on the programmatic model, and earlier ideas from the Russian gerontologist Vladimir Dilman, to explain the origins of diseases of aging.[13]

He has written on the ethics of research on aging, mainly arguing against conservative objections to intervening in the aging process,[28] and the traditional medical view that diseases of aging are something apart from the process of normal aging.[29] He is said to be working (2023) on a book on developments in the science of ageing.

References

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  1. ^ "Institute of Healthy Ageing (IHA)". UCL Division of Biosciences. 22 March 2019.
  2. ^ "Institute of Healthy Ageing - People", accessed November 21, 2010.
  3. ^ "C. elegans Ageing Laboratory", accessed November 21, 2010.
  4. ^ a b "David Gems Profile", accessed November 21, 2010.
  5. ^ "Donald L. Riddle". nemaplex.ucdavis.edu. Retrieved 23 July 2023.
  6. ^ UCL (29 January 2021). "History". UCL Division of Biosciences. Retrieved 23 July 2023.
  7. ^ "Clancy, David; Gems, David; Leevers, Sally J; Oldham, Sean; Stocker, Hugo; Hafen, Ernst; Harshman, Laurence; Partridge, Linda (2001) "Extension of life span by loss of CHICO, a Drosophila insulin receptor substrate protein"". Science.
  8. ^ "Selman, Colin, Lingard, Steven, Gems, David; Partridge, Linda; Withers, Dominic J. (2008) "Extended lifespan with reduced age-related pathology in insulin receptor substrate 1 null mice"". FASEB Journal.
  9. ^ "Keaney, Michele; Gems, David (2003) "No increase in life span in Caenorhabditis elegans upon treatment with the superoxide dismutase mimetic EUK-8"". Free Radical Biology and Medicine.
  10. ^ "Doonan, Ryan; McElwee, Joshua J.; Matthijssens, Filip; Walker, Glenda A.; Houthoofd, Koen; Back, Patricia; Matscheski, Andrea; Vanfleteren, Jacques R; Gems, David (2008) "Against the oxidative damage theory of aging: Superoxide dismutases protect against oxidative stress but have little or no effect on lifespan in C. elegans"". Genes and Development.
  11. ^ "Cabreiro, Filipe; Ackerman, Daniel; Doonan, Ryan; Araiz, Caroline; Back, Patricia; Papp, Diana; Braeckman, Bart P.; Gems, David (2011) "Increased lifespan from over-expression of superoxide dismutase in C. elegans is not caused by decreased oxidative damage"". Free Radical Biology and Medicine.
  12. ^ "Gems, David, Doonan, Ryan (2009) "Antioxidant defense and aging in C. elegans: Is the oxidative damage theory of aging wrong?"". Cell Cycle.
  13. ^ a b c Gems, David (2022). "The hyperfunction theory: an emerging paradigm for the biology of aging". Ageing Research Reviews. 74: 101557. doi:10.1016/j.arr.2021.101557. PMC 7612201. PMID 34990845.
  14. ^ Williams, George C. (1957). "Pleiotropy, natural selection and the evolution of senescence". Evolution. 11 (4): 398–411. doi:10.2307/2406060. JSTOR 2406060.
  15. ^ Blagosklonny, Mikhail V. (2006). "Aging and immortality: quasi-programmed senescence and its pharmacologic inhibition". Cell Cycle. 5 (18): 2087–2102. doi:10.4161/cc.5.18.3288. PMID 17012837. S2CID 24475537.
  16. ^ De Magalhães, João Pedro; Church, George M. (2005). "Genomes Optimize Reproduction: Aging as a Consequence of the Developmental Program". Physiology. 20 (4): 252–259. doi:10.1152/physiol.00010.2005. PMID 16024513.
  17. ^ Kern, Carina; Faragher, Richard; Jenkins, Annalisa; Stebbing, Justin (2024). "Uncovering the Blueprint Theory of Ageing". Preprints. doi:10.20944/preprints202310.1387.v3.
  18. ^ Gems, David; de la Guardia, Yila (2013). "Alternative perspectives on aging in C. elegans: reactive oxygen species or hyperfunction?". Antioxidants & Redox Signaling. 19 (3): 321–329. doi:10.1089/ars.2012.4840. PMC 5395017. PMID 22870907.
  19. ^ de la Guardia, Yila; Gilliat, Ann F.; Hellberg, Josephine; Rennert, Peter; Cabreiro, Filipe; Gems, David (2016). "Run-on of germline apoptosis promotes gonad senescence in C. Elegans". Oncotarget. 7 (26): 39082–39096. doi:10.18632/oncotarget.9681. PMC 5129915. PMID 27256978.
  20. ^ Wang, Hongyuan; et al. (2018). "A parthenogenetic quasi-program causes teratoma-like tumors during aging in wild-type C. elegans". npj Aging and Mechanisms of Disease. 4: 6. doi:10.1038/s41514-018-0025-3. PMC 5998035. PMID 29928508.
  21. ^ Ezcurra, Marina; et al. (2018). "C. elegans eats its own intestine to make yolk leading to multiple senescent pathologies". Current Biology. 28 (16): 2544–2556.e5. Bibcode:2018CBio...28E2544E. doi:10.1016/j.cub.2018.06.035. PMC 6108400. PMID 30100339.
  22. ^ Gems, David; Partridge, Linda (2013). "Genetics of longevity in model organisms: debates and paradigm shifts". Annual Review of Physiology. 75: 621–644. doi:10.1146/annurev-physiol-030212-183712. PMID 23190075.
  23. ^ Gems, David; de Magalhães, João Pedro (2021). "The hoverfly and the wasp: A critique of the hallmarks of aging as a paradigm". Ageing Research Reviews. 70: 101407. doi:10.1016/j.arr.2021.101407. PMC 7611451. PMID 34271186.
  24. ^ Gems, David; Kern, Carina C. (2022). "Is 'cellular senescence' a misnomer?". GeroScience. 44 (5): 2461–2469. doi:10.1007/s11357-022-00652-x. PMC 9768054. PMID 36068483.
  25. ^ doi:10.1016/j.arr.2019.01.008
  26. ^ Gems, David; Kern, Carina C.; Nour, Joseph; Ezcurra, Marina (2021). "Reproductive Suicide: Similar Mechanisms of Aging in C. Elegans and Pacific Salmon". Frontiers in Cell and Developmental Biology. 9: 688788. doi:10.3389/fcell.2021.688788. PMC 8430333. PMID 34513830.
  27. ^ Kern, Carina C.; Gems, David (2022). "Semelparous Death as one Element of Iteroparous Aging Gone Large". Frontiers in Genetics. 13: 880343. doi:10.3389/fgene.2022.880343. PMC 9218716. PMID 35754809.
  28. ^ Gems, David (2003). "Is more life always better? Problems arising from the new biology of aging". Hastings Center Report. doi:10.2307/3528378. JSTOR 3528378.
  29. ^ Gems, David (2015). "The aging-disease false dichotomy: Understanding senescence as pathology". Frontiers in Genetics. 6: 212. doi:10.3389/fgene.2015.00212. PMC 4468941. PMID 26136770.
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