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Perturbation as method of research on metabolic organisation of individuals

Exploring the effects of toxicants on energetics and ageing through perturbation analysis in metabolic research by Bas Kooijman at Vrije Universiteit Amsterdam. The theory covers damage-inducing compounds' generation, survival probability in aging, and the impact of energy investment ratios on aging between sexes. The study also delves into the relationship of O2 use, feeding behaviors, and age-dependent physiological changes in various species, revealing key insights into the metabolic organization of individuals.

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Perturbation as method of research on metabolic organisation of individuals

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  1. Perturbation as method of research on metabolic organisation of individuals Bas Kooijman Dept theoretical biology Vrije Universiteit Amsterdam Bas@bio.vu.nl http://www.bio.vu.nl/thb/ Glasgow, 2009/07/01

  2. Perturbation as method of research on metabolic organisation of individuals Bas Kooijman Dept theoretical biology Vrije Universiteit Amsterdam Bas@bio.vu.nl http://www.bio.vu.nl/thb/ • Contents: • Ageing • Effects of energetics on ageing • Effects of toxicants on energetics • Effects of toxicants on ageing • Thank you Glasgow, 2009/07/01

  3. Aging module of DEB theory • damage-inducing compounds (modified nuclear and mitochondrial DNA) are generated at a rate  reserve mobilisation rate • damage-inducing compounds induce themselves at a rate  mobilisation rate • damage-inducing compounds generate damage compounds (`wrong' proteins) at constant rate, which cumulate in the body • hazard rate  density of damage compounds

  4. Aging module of DEB theory

  5. Aging: non-growing ectotherms 6.1.1 survival prob Weibull with shape parameter 3 time, d Drosophila melanogaster Data: Rose 1984

  6. Aging: growing ectotherms 6.1.1 survival prob body weight, g time, d time, d Weibull with shape 3 fits ectothermic survival well, even if growth period not small relative to life span Lymnaea stagnalis Data: Slob & Janse 1988

  7. Aging: relation to O2-use 6.1 survival prob Reodruction rate, #/d 0.374 high food 10/20°C high food 10/10°C low food 10/20°C 0.547 0.630 time, d time, d Differences in life span are caused by differences in respiration Notiophilus biguttatus Data: Ernsting & Isaaks 1997

  8. Aging: sex differentiation survival prob body weight, g time, d time, d Differences in aging between sexes are caused by differences in energy investment ratio g i.e. by max spec assimilation rate Daphnia magna Data: MacArthur & Baillie 1929

  9. Aging: ectotherms & feeding survival prob body length, cm • ad libitum • restricted 100-600 d time, d time, d Poecilia reticulata Data: Comfort, 1963

  10. Aging: endotherms & feeding feeding level 1 body weight, g embryo weight, g 0.75 0.44 time, d time, d 0.44 survival prob • Life span • hardly depends on food in ecotherms • decreases for increasing food in endotherms 0.75 1 time, d Mus musculus Data: Weindruch et al 1986 MacDowell et al 1927

  11. Effect of feeding on ageing: RNS Hazard rate, d-1 Aging acceleration, 0.001 d-2 Ultimate volume 10-12 m3 age, d age, d Food levels: 20, 30, 60, 120, 240 paramecia d-1 rotifer-1 Aging acceleration linear in food level Asplanchna girodi Data: Robertson & Salt 1981 Suggestion: Paramecia are rich in NO32- & NO22-from lettuce, which enhances ageing

  12. Aging among species Right whale slope 1/3, 1/5 Ricklefs & Finch 1995 • Conclusion for life span • hardly depends on max body size of ectotherms • increases with length in endotherms

  13. Toxic effect on survival Dieldrin affects survival hazard rate  internal conc one-compartment kinetics killing rate 0.038 l g-1 d-1 elimination rate 0.712 d-1 NEC 4.49 g l-1 Poecilia reticulata Data: Adema, unpubl.

  14. assimilation  maintenance costs defecation feeding food faeces growth costs assimilation reproduction costs reserve  hazard to embryo somatic maintenance  7 maturity maintenance  1-  maint tumour induction 6 maturation reproduction u endocr. disruption growth 7  lethal effects: hazard rate Mode of action affects translation to pop level 8 maturity offspring structure tumour 6 Modes of action of toxicants Embryo: no feeding; Juvenile: no reprod

  15. Change in target parameter Simplest basis: Change  internal conc that exceeds internal NEC or with • Rationale • effective molecules • operate independently • approximation • for small effects

  16. indirect effects mg L-1 Effects on reproduction 0, 320 assimilation 560 1000 cum # offspring/♀ 1800 Daphnia magna Phenol, 20°C 3200 direct effects maintenance cost/offspring cum # offspring/♀ growth hazard cum # offspring/♀ time, d time, d

  17. Embryonic development Crocodylus johnstoni, Data: Whitehead 1987 embryo yolk O2 consumption, ml/h weight, g time, d time, d Birth (= start of assimilation): maturity exceeds threshold Maternal effect: reserve density at birth equals that of mother Implication of increase of cost of structure: - allocation to reproduction decreases - structure at birth decreases  cost of egg decreases - hormesis: increase of reproduction rate at low effect levels

  18. TPT body length cumulative offspring time time Increase in maintenance costs Folsomia candida Tri-Phenyl-Tin Jager et al. (2004)

  19. Pentachlorobenzene body length cumulative offspring time time Increase in cost for structure Caenorhabditis elegans Alda Álvarez et al. (2006)

  20. Chlorpyrifos body length cumulative offspring time time Increase in cost for offspring Folsomia candida Jager et al. (2007)

  21. 200 65 180 60 160 55 140 50 120 45 cumulative offspring per female 100 body length 40 80 35 60 30 40 25 20 20 0 0 5 10 15 20 15 0 5 10 15 20 25 30 time time Decrease in assimilationsomatic maint coeff = maturity maint coeff Acrobeloides nanus Pentachlorobenzene Data: Alda Álvarez et al (2006) Fit: Jager

  22. 180 65 160 60 140 55 120 50 100 cumulative offspring per female 45 80 body length 40 60 35 40 30 20 25 0 20 0 5 10 15 20 15 time 0 5 10 15 20 25 30 35 time Increase cost for structure Acrobeloides nanus Cadmium Data: Alda Álvarez et al (2006) Fit: Jager

  23. 180 65 60 160 55 140 50 120 45 100 cumulative offspring per female body length 40 80 35 60 30 40 25 20 20 0 15 0 5 10 15 20 0 5 10 15 20 25 30 35 time time Increase cost for structureDecrease in maturity maintenance Acrobeloides nanus Cadmium Data: Alda Álvarez et al (2006) Fit: Jager

  24. 65 180 60 160 55 140 50 120 45 100 cumulative offspring per female body length 40 80 35 60 30 40 25 20 20 15 0 0 5 10 15 20 25 30 35 0 5 10 15 20 time time Increase cost for structureDecrease in maturity maintenanceIncrease of ageing Acrobeloides nanus Cadmium Data: Alda Álvarez et al (2006) Fit: Jager

  25. time (days) Toxicants affect ageing Folsomia candida cadmium time (days) Jager et al. (2004)

  26. DEB tele course 2011 http://www.bio.vu.nl/thb/deb/ Free of financial costs; some 200 h effort investment 5w Feb-Mar + 5w Sept-Oct + symposium in Lisboa 10-16 Apr 2011 target audience: PhD students We encourage participation in groups that organize local meetings weekly Participants of previous DEB tele courses 2005 created AQUAdeb: special issues of J Sea Res 2006, 2009 theme issue of Phil Trans Royal Soc 2010 on DEB applications Software package DEBtool for Octave/ Matlab freely downloadable Slides of this presentation are downloadable from http://www.bio.vu.nl/thb/users/bas/lectures/ Organisors: thank you for all your work Audience: thank you for your attention

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