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A New, Discontinuous 2 Phases of Aging Model: Lessons from Drosophila melanogaster.

Tricoire H, Rera M - PLoS ONE (2015)

Bottom Line: We first present a unique equation for each phase and discuss the biological significance of the 3 associated parameters.Overall, this new mathematical model, based on simple biological observations, is able to reproduce many experimental longevity curves, supporting the existence of 2 phases of aging exhibiting specific properties and separated by a dramatic transition that remains to be characterized.Moreover, it indicates that Smurf survival can be approximated by one single constant parameter for a broad range of genotypes that we have tested under our environmental conditions.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Degenerative Processes, Stress and Aging, UMR8251, Université Paris Diderot, Paris 75013, France.

ABSTRACT
Aging is commonly described as being a continuous process affecting progressively organisms as time passes. This process results in a progressive decrease in individuals fitness through a wide range of both organismal-decreased motor activity, fertility, resistance to stress-and molecular phenotypes-decreased protein and energy homeostasis, impairment of insulin signaling. In the past 20 years, numerous genes have been identified as playing a major role in the aging process, yet little is known about the events leading to that loss of fitness. We recently described an event characterized by a dramatic increase of intestinal permeability to a blue food dye in aging flies committed to die within a few days. Importantly, flies showing this so called 'Smurf' phenotype are the only ones, among a population, to show various age-related changes and exhibit a high-risk of impending death whatever their chronological age. Thus, these observations suggest that instead of being one continuous phenomenon, aging may be a discontinuous process well described by at least two distinguishable phases. In this paper we addressed this hypothesis by implementing a new 2 Phases of Aging mathematiCal model (2PAC model) to simulate longevity curves based on the simple hypothesis of two consecutive phases of lifetime presenting different properties. We first present a unique equation for each phase and discuss the biological significance of the 3 associated parameters. Then we evaluate the influence of each parameter on the shape of survival curves. Overall, this new mathematical model, based on simple biological observations, is able to reproduce many experimental longevity curves, supporting the existence of 2 phases of aging exhibiting specific properties and separated by a dramatic transition that remains to be characterized. Moreover, it indicates that Smurf survival can be approximated by one single constant parameter for a broad range of genotypes that we have tested under our environmental conditions.

No MeSH data available.


Related in: MedlinePlus

The remaining lifespan of individuals in phase 2 is similar in different drosophila strains.A. Mated females from populations of 6 different genetic backgrounds show significant different lifespan curves, DGRP_83 (T50 = 42 days; n = 128), DGRP_88 (T50 = 39.6 days; n = 127), DGRP_91 (T50 = 52.7 days; n = 340), DGRP_105 (T50 = 57.1 days; n = 286), DGRP_136 (T50 = 53.4 days; n = 243) and DGRP_195 (T50 = 32.9 days; n = 262). B, C. The life expectancies of Smurfs from the 6 DGRP lines are highly similar, DGRP_83 (T50 = 4.0 days; n = 31), DGRP_88 (T50 = 2.3 days; n = 45), DGRP_91 (T50 = 5.0 days; n = 96), DGRP_105 (T50 = 3.1 days; n = 75), DGRP_136 (T50 = 3.0 days; n = 56) and DGRP_195 (T50 = 2.9 days; n = 63). In addition, none is different from the one measured using 1146 drsGFP individual flies (p > 0.05, 1-way ANOVA using the drsGFP as reference) although the Smurf survival measurement protocol was different. Error bars represent median ± s.e.m. D-F. Although SIRs of DGRP_195 (0.01832 ± 0.001602; R2 = 0.5612) and DGRP_105 (0.003623 ± 0.001602; R2 = 0.8127) are significantly different (p = 0.01579, N > 5 vials per genotype), it is possible to model the longevity curves of the two genotypes using the same k (phase 2) parameter (calculated from drsGFP Smurf flies–Fig 3C) with R2 > 0.99. Error bars represent mean ± s.e.m. Note concerning Fig 4B and 4C:the T50are higher in fig C than B and this is due to averaging individual vials for the ANOVA test instead of calculating one T50using the whole population.
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pone.0141920.g004: The remaining lifespan of individuals in phase 2 is similar in different drosophila strains.A. Mated females from populations of 6 different genetic backgrounds show significant different lifespan curves, DGRP_83 (T50 = 42 days; n = 128), DGRP_88 (T50 = 39.6 days; n = 127), DGRP_91 (T50 = 52.7 days; n = 340), DGRP_105 (T50 = 57.1 days; n = 286), DGRP_136 (T50 = 53.4 days; n = 243) and DGRP_195 (T50 = 32.9 days; n = 262). B, C. The life expectancies of Smurfs from the 6 DGRP lines are highly similar, DGRP_83 (T50 = 4.0 days; n = 31), DGRP_88 (T50 = 2.3 days; n = 45), DGRP_91 (T50 = 5.0 days; n = 96), DGRP_105 (T50 = 3.1 days; n = 75), DGRP_136 (T50 = 3.0 days; n = 56) and DGRP_195 (T50 = 2.9 days; n = 63). In addition, none is different from the one measured using 1146 drsGFP individual flies (p > 0.05, 1-way ANOVA using the drsGFP as reference) although the Smurf survival measurement protocol was different. Error bars represent median ± s.e.m. D-F. Although SIRs of DGRP_195 (0.01832 ± 0.001602; R2 = 0.5612) and DGRP_105 (0.003623 ± 0.001602; R2 = 0.8127) are significantly different (p = 0.01579, N > 5 vials per genotype), it is possible to model the longevity curves of the two genotypes using the same k (phase 2) parameter (calculated from drsGFP Smurf flies–Fig 3C) with R2 > 0.99. Error bars represent mean ± s.e.m. Note concerning Fig 4B and 4C:the T50are higher in fig C than B and this is due to averaging individual vials for the ANOVA test instead of calculating one T50using the whole population.

Mentions: We previously showed that the rate at which the proportion of Smurfs increases in a population negatively correlates with the T50 of that population [1]. We identified 6 lines–from the Drosophila melanogaster Genetic Reference Panel (DGRP) [15]–, characterized by significantly different lifespans showing T50 values ranging from 32 to 57.7 days (Fig 4A). Using the previously described methodology to identify Smurf flies, we isolated Smurfs at different ages (15, 23, 33, 41, 47, 55 and 62 days) from the 6 populations of DGRP flies presented in Fig 4A and monitored their remaining lifespan (Fig 4B). Although these survival curves don’t totally overlap they are highly similar, with T50 values showing no significant differences with the drsGFP large dataset (Fig 4C).


A New, Discontinuous 2 Phases of Aging Model: Lessons from Drosophila melanogaster.

Tricoire H, Rera M - PLoS ONE (2015)

The remaining lifespan of individuals in phase 2 is similar in different drosophila strains.A. Mated females from populations of 6 different genetic backgrounds show significant different lifespan curves, DGRP_83 (T50 = 42 days; n = 128), DGRP_88 (T50 = 39.6 days; n = 127), DGRP_91 (T50 = 52.7 days; n = 340), DGRP_105 (T50 = 57.1 days; n = 286), DGRP_136 (T50 = 53.4 days; n = 243) and DGRP_195 (T50 = 32.9 days; n = 262). B, C. The life expectancies of Smurfs from the 6 DGRP lines are highly similar, DGRP_83 (T50 = 4.0 days; n = 31), DGRP_88 (T50 = 2.3 days; n = 45), DGRP_91 (T50 = 5.0 days; n = 96), DGRP_105 (T50 = 3.1 days; n = 75), DGRP_136 (T50 = 3.0 days; n = 56) and DGRP_195 (T50 = 2.9 days; n = 63). In addition, none is different from the one measured using 1146 drsGFP individual flies (p > 0.05, 1-way ANOVA using the drsGFP as reference) although the Smurf survival measurement protocol was different. Error bars represent median ± s.e.m. D-F. Although SIRs of DGRP_195 (0.01832 ± 0.001602; R2 = 0.5612) and DGRP_105 (0.003623 ± 0.001602; R2 = 0.8127) are significantly different (p = 0.01579, N > 5 vials per genotype), it is possible to model the longevity curves of the two genotypes using the same k (phase 2) parameter (calculated from drsGFP Smurf flies–Fig 3C) with R2 > 0.99. Error bars represent mean ± s.e.m. Note concerning Fig 4B and 4C:the T50are higher in fig C than B and this is due to averaging individual vials for the ANOVA test instead of calculating one T50using the whole population.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4631373&req=5

pone.0141920.g004: The remaining lifespan of individuals in phase 2 is similar in different drosophila strains.A. Mated females from populations of 6 different genetic backgrounds show significant different lifespan curves, DGRP_83 (T50 = 42 days; n = 128), DGRP_88 (T50 = 39.6 days; n = 127), DGRP_91 (T50 = 52.7 days; n = 340), DGRP_105 (T50 = 57.1 days; n = 286), DGRP_136 (T50 = 53.4 days; n = 243) and DGRP_195 (T50 = 32.9 days; n = 262). B, C. The life expectancies of Smurfs from the 6 DGRP lines are highly similar, DGRP_83 (T50 = 4.0 days; n = 31), DGRP_88 (T50 = 2.3 days; n = 45), DGRP_91 (T50 = 5.0 days; n = 96), DGRP_105 (T50 = 3.1 days; n = 75), DGRP_136 (T50 = 3.0 days; n = 56) and DGRP_195 (T50 = 2.9 days; n = 63). In addition, none is different from the one measured using 1146 drsGFP individual flies (p > 0.05, 1-way ANOVA using the drsGFP as reference) although the Smurf survival measurement protocol was different. Error bars represent median ± s.e.m. D-F. Although SIRs of DGRP_195 (0.01832 ± 0.001602; R2 = 0.5612) and DGRP_105 (0.003623 ± 0.001602; R2 = 0.8127) are significantly different (p = 0.01579, N > 5 vials per genotype), it is possible to model the longevity curves of the two genotypes using the same k (phase 2) parameter (calculated from drsGFP Smurf flies–Fig 3C) with R2 > 0.99. Error bars represent mean ± s.e.m. Note concerning Fig 4B and 4C:the T50are higher in fig C than B and this is due to averaging individual vials for the ANOVA test instead of calculating one T50using the whole population.
Mentions: We previously showed that the rate at which the proportion of Smurfs increases in a population negatively correlates with the T50 of that population [1]. We identified 6 lines–from the Drosophila melanogaster Genetic Reference Panel (DGRP) [15]–, characterized by significantly different lifespans showing T50 values ranging from 32 to 57.7 days (Fig 4A). Using the previously described methodology to identify Smurf flies, we isolated Smurfs at different ages (15, 23, 33, 41, 47, 55 and 62 days) from the 6 populations of DGRP flies presented in Fig 4A and monitored their remaining lifespan (Fig 4B). Although these survival curves don’t totally overlap they are highly similar, with T50 values showing no significant differences with the drsGFP large dataset (Fig 4C).

Bottom Line: We first present a unique equation for each phase and discuss the biological significance of the 3 associated parameters.Overall, this new mathematical model, based on simple biological observations, is able to reproduce many experimental longevity curves, supporting the existence of 2 phases of aging exhibiting specific properties and separated by a dramatic transition that remains to be characterized.Moreover, it indicates that Smurf survival can be approximated by one single constant parameter for a broad range of genotypes that we have tested under our environmental conditions.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Degenerative Processes, Stress and Aging, UMR8251, Université Paris Diderot, Paris 75013, France.

ABSTRACT
Aging is commonly described as being a continuous process affecting progressively organisms as time passes. This process results in a progressive decrease in individuals fitness through a wide range of both organismal-decreased motor activity, fertility, resistance to stress-and molecular phenotypes-decreased protein and energy homeostasis, impairment of insulin signaling. In the past 20 years, numerous genes have been identified as playing a major role in the aging process, yet little is known about the events leading to that loss of fitness. We recently described an event characterized by a dramatic increase of intestinal permeability to a blue food dye in aging flies committed to die within a few days. Importantly, flies showing this so called 'Smurf' phenotype are the only ones, among a population, to show various age-related changes and exhibit a high-risk of impending death whatever their chronological age. Thus, these observations suggest that instead of being one continuous phenomenon, aging may be a discontinuous process well described by at least two distinguishable phases. In this paper we addressed this hypothesis by implementing a new 2 Phases of Aging mathematiCal model (2PAC model) to simulate longevity curves based on the simple hypothesis of two consecutive phases of lifetime presenting different properties. We first present a unique equation for each phase and discuss the biological significance of the 3 associated parameters. Then we evaluate the influence of each parameter on the shape of survival curves. Overall, this new mathematical model, based on simple biological observations, is able to reproduce many experimental longevity curves, supporting the existence of 2 phases of aging exhibiting specific properties and separated by a dramatic transition that remains to be characterized. Moreover, it indicates that Smurf survival can be approximated by one single constant parameter for a broad range of genotypes that we have tested under our environmental conditions.

No MeSH data available.


Related in: MedlinePlus