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Maklakov, Alexei
Alternative names
Publications (10 of 58) Show all publications
Lind, M. I., Ravindran, S., Sekajova, Z., Carlsson, H., Hinas, A. & Maklakov, A. A. (2019). Experimentally reduced insulin/IGF‐1 signaling in adulthood extends lifespan of parents and improves Darwinian fitness of their offspring. EVOLUTION LETTERS, 3(2), 207-216
Open this publication in new window or tab >>Experimentally reduced insulin/IGF‐1 signaling in adulthood extends lifespan of parents and improves Darwinian fitness of their offspring
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2019 (English)In: EVOLUTION LETTERS, ISSN 2056-3744, Vol. 3, no 2, p. 207-216Article in journal (Refereed) Published
Abstract [en]

Classical theory maintains that ageing evolves via energy trade-offs between reproduction and survival leading to accumulation of unrepaired cellular damage with age. In contrast, the emerging new theory postulates that ageing evolves because of deleterious late-life hyper-function of reproduction-promoting genes leading to excessive biosynthesis in late-life. The hyper-function theory uniquely predicts that optimizing nutrient-sensing molecular signaling in adulthood can simultaneously postpone ageing and increase Darwinian fitness. Here, we show that reducing evolutionarily conserved insulin/IGF-1 nutrient-sensing signaling via daf-2 RNA interference (RNAi) fulfils this prediction in Caenorhabditis elegans nematodes. Long-lived daf-2 RNAi parents showed normal fecundity as self-fertilizing hermaphrodites and improved late-life reproduction when mated to males. Remarkably, the offspring of daf-2 RNAi parents had higher Darwinian fitness across three different genotypes. Thus, reduced nutrient-sensing signaling in adulthood improves both parental longevity and offspring fitness supporting the emerging view that suboptimal gene expression in late-life lies at the heart of ageing.

Keywords
Ageing, antagonistic pleiotropy, functional trade-offs, hyperfunction, IIS signaling, parental effects, senescence
National Category
Genetics
Identifiers
urn:nbn:se:uu:diva-382655 (URN)10.1002/evl3.108 (DOI)000463987900009 ()31007945 (PubMedID)
Funder
EU, European Research Council, 724909Swedish Research Council, 2016-05195
Available from: 2019-04-29 Created: 2019-04-29 Last updated: 2019-04-29Bibliographically approved
Alavioon, G., Garcia, A. C., LeChatelier, M., Maklakov, A. A. & Immler, S. (2019). Selection for longer lived sperm within ejaculate reduces reproductive ageing in offspring. EVOLUTION LETTERS, 3(2), 198-206
Open this publication in new window or tab >>Selection for longer lived sperm within ejaculate reduces reproductive ageing in offspring
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2019 (English)In: EVOLUTION LETTERS, ISSN 2056-3744, Vol. 3, no 2, p. 198-206Article in journal (Refereed) Published
Abstract [en]

Males produce numerous sperm in a single ejaculate that greatly outnumber their potential egg targets. Recent studies found that phenotypic and genotypic variation among sperm in a single ejaculate of a male affects the fitness and performance of the resulting offspring. Specifically, within-ejaculate sperm selection for sperm longevity increased the performance of the resulting offspring in several key life-history traits in early life. Because increased early-life reproductive performance often correlates with rapid ageing, it is possible that within-ejaculate sperm selection increases early-life fitness at the cost of accelerated senescence. Alternatively, within-ejaculate sperm selection could improve offspring quality throughout the life cycle, including reduced age-specific deterioration. We tested the two alternative hypotheses in an experimental setup using zebrafish Danio rerio. We found that within-ejaculate sperm selection for sperm longevity reduced age-specific deterioration of fecundity and offspring survival but had no effect on fertilization success in males. Remarkably, we found an opposing effect of within-ejaculate sperm selection on female fecundity, where selection for sperm longevity resulted in increased early-life performance followed by a slow decline, while females sired by unselected sperm started low but increased their fecundity with age. Intriguingly, within-ejaculate sperm selection also reduced the age-specific decline in fertilization success in females, suggesting that selection for sperm longevity improves at least some aspects of female reproductive ageing. These results demonstrate that within-ejaculate variation in sperm phenotype contributes to individual variation in animal life histories in the two sexes and may have important implications for assisted fertilization programs in livestock and humans.

Keywords
Ageing, reproductive success, sperm selection, sperm competition, senescence
National Category
Evolutionary Biology
Identifiers
urn:nbn:se:uu:diva-382654 (URN)10.1002/evl3.101 (DOI)000463987900008 ()
Funder
EU, European Research Council, HapSelA 336633Knut and Alice Wallenberg Foundation
Available from: 2019-04-29 Created: 2019-04-29 Last updated: 2019-04-29Bibliographically approved
Erkosar, B., Yashiro, E., Zajitschek, F., Friberg, U., Maklakov, A. A., van der Meer, J. R. & Kawecki, T. J. (2018). Host diet mediates a negative relationship between abundance and diversity of Drosophila gut microbiota. Ecology and Evolution, 8(18), 9491-9502
Open this publication in new window or tab >>Host diet mediates a negative relationship between abundance and diversity of Drosophila gut microbiota
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2018 (English)In: Ecology and Evolution, ISSN 2045-7758, E-ISSN 2045-7758, Vol. 8, no 18, p. 9491-9502Article in journal (Refereed) Published
Abstract [en]

Nutrient supply to ecosystems has major effects on ecological diversity, but it is unclear to what degree the shape of this relationship is general versus dependent on the specific environment or community. Although the diet composition in terms of the source or proportions of different nutrient types is known to affect gut microbiota composition, the relationship between the quantity of nutrients supplied and the abundance and diversity of the intestinal microbial community remains to be elucidated. Here, we address this relationship using replicate populations of Drosophila melanogaster maintained over multiple generations on three diets differing in the concentration of yeast (the only source of most nutrients). While a 6.5-fold increase in yeast concentration led to a 100-fold increase in the total abundance of gut microbes, it caused a major decrease in their alpha diversity (by 45-60% depending on the diversity measure). This was accompanied by only minor shifts in the taxonomic affiliation of the most common operational taxonomic units (OTUs). Thus, nutrient concentration in host diet mediates a strong negative relationship between the nutrient abundance and microbial diversity in the Drosophila gut ecosystem.

Place, publisher, year, edition, pages
WILEY, 2018
Keywords
diet, Drosophila, host-microbe interactions, intermediate productivity hypothesis, microbiota, productivity-diversity relationship
National Category
Ecology
Identifiers
urn:nbn:se:uu:diva-364852 (URN)10.1002/ece3.4444 (DOI)000447756100030 ()30377517 (PubMedID)
Funder
EU, European Research CouncilSwedish Research CouncilWenner-Gren Foundations
Available from: 2018-11-05 Created: 2018-11-05 Last updated: 2019-01-21Bibliographically approved
Griffin, R. M., Hayward, A. D., Bolund, E., Maklakov, A. A. & Lummaa, V. (2018). Sex differences in adult mortality rate mediated by early-life environmental conditions. Ecology Letters, 21(2), 235-242
Open this publication in new window or tab >>Sex differences in adult mortality rate mediated by early-life environmental conditions
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2018 (English)In: Ecology Letters, ISSN 1461-023X, E-ISSN 1461-0248, Vol. 21, no 2, p. 235-242Article in journal (Refereed) Published
Abstract [en]

Variation in sex differences is affected by both genetic and environmental variation, with rapid change in sex differences being more likely due to environmental change. One case of rapid change in sex differences is human lifespan, which has become increasingly female-biased in recent centuries. Long-term consequences of variation in the early-life environment may, in part, explain such variation in sex differences, but whether the early-life environment mediates sex differences in life-history traits is poorly understood in animals. Combining longitudinal data on 60 cohorts of pre-industrial Finns with environmental data, we show that the early-life environment is associated with sex differences in adult mortality and expected lifespan. Specifically, low infant survival rates and high rye yields (an important food source) in early-life are associated with female-bias in adult lifespan. These results support the hypothesis that environmental change has the potential to affect sex differences in life-history traits in natural populations of long-lived mammals.

Place, publisher, year, edition, pages
WILEY, 2018
Keywords
Development, environmental variation, humans, life-history, sexual dimorphism
National Category
Evolutionary Biology
Identifiers
urn:nbn:se:uu:diva-349833 (URN)10.1111/ele.12888 (DOI)000425823900009 ()29210148 (PubMedID)
Funder
Swedish Research CouncilEU, European Research Council
Available from: 2018-05-07 Created: 2018-05-07 Last updated: 2018-05-07Bibliographically approved
Maklakov, A. A., Carlsson, H., Denbaum, P., Lind, M. I., Mautz, B., Hinas, A. & Immler, S. (2017). Antagonistically pleiotropic allele increases lifespan and late-life reproduction at the cost of early-life reproduction and individual fitness. Proceedings of the Royal Society of London. Biological Sciences, 284(1856), Article ID 20170376.
Open this publication in new window or tab >>Antagonistically pleiotropic allele increases lifespan and late-life reproduction at the cost of early-life reproduction and individual fitness
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2017 (English)In: Proceedings of the Royal Society of London. Biological Sciences, ISSN 0962-8452, E-ISSN 1471-2954, Vol. 284, no 1856, article id 20170376Article in journal (Refereed) Published
Abstract [en]

Evolutionary theory of ageing maintains that increased allocation to early-life reproduction results in reduced somatic maintenance, which is predicted to compromise longevity and late-life reproduction. This prediction has been challenged by the discovery of long-lived mutants with no loss of fecundity. The first such long-lived mutant was found in the nematode worm Caenorhabditis elegans. Specifically, partial loss-of-function mutation in the age-1 gene, involved in the nutrient-sensing insulin/insulin-like growth factor signalling pathway, confers longevity, as well as increased resistance to pathogens and to temperature stress without appreciable fitness detriment. Here, we show that the long-lived age-1(hx546) mutant has reduced fecundity and offspring production in early-life, but increased fecundity, hatching success, and offspring production in late-life compared with wild-type worms under standard conditions. However, reduced early-life performance of long-lived mutant animals was not fully compensated by improved performance in late-life and resulted in reduced individual fitness. These results suggest that the age-1(hx546) allele has opposing effects on early-life versus late-life fitness in accordance with antagonistic pleiotropy (AP) and disposable soma theories of ageing. These findings support the theoretical conjecture that experimental studies based on standing genetic variation underestimate the importance of AP in the evolution of ageing.

Place, publisher, year, edition, pages
ROYAL SOC, 2017
Keywords
ageing, senescence, life history
National Category
Biological Sciences
Identifiers
urn:nbn:se:uu:diva-331255 (URN)10.1098/rspb.2017.0376 (DOI)000405955300010 ()
Funder
EU, European Research Council, AGINGSEXDIFF 260885, HAPSELA 336633Swedish Research Council, 2013-04828
Available from: 2017-10-24 Created: 2017-10-24 Last updated: 2017-10-24Bibliographically approved
Zwoinska, M. K., Maklakov, A. A., Kawecki, T. J. & Hollis, B. (2017). Experimental evolution of slowed cognitive aging in Drosophila melanogaster. Evolution, 71(3), 662-670
Open this publication in new window or tab >>Experimental evolution of slowed cognitive aging in Drosophila melanogaster
2017 (English)In: Evolution, ISSN 0014-3820, E-ISSN 1558-5646, Vol. 71, no 3, p. 662-670Article in journal (Refereed) Published
Abstract [en]

Reproductive output and cognitive performance decline in parallel during aging, but it is unknown whether this reflects a shared genetic architecture or merely the declining force of natural selection acting independently on both traits. We used experimental evolution in Drosophila melanogaster to test for the presence of genetic variation for slowed cognitive aging, and assess its independence from that responsible for other traits' decline with age. Replicate experimental populations experienced either joint selection on learning and reproduction at old age (Old + Learning), selection on late-life reproduction alone (Old), or a standard two-week culture regime (Young). Within 20 generations, the Old + Learning populations evolved a slower decline in learning with age than both the Old and Young populations, revealing genetic variation for cognitive aging. We found little evidence for a genetic correlation between cognitive and demographic aging: although the Old + Learning populations tended to show higher late-life fecundity than Old populations, they did not live longer. Likewise, selection for late reproduction alone did not result in improved late-life learning. Our results demonstrate that Drosophila harbor genetic variation for cognitive aging that is largely independent from genetic variation for demographic aging and suggest that these two aspects of aging may not necessarily follow the same trajectories.

Place, publisher, year, edition, pages
WILEY, 2017
Keywords
Cognitive aging, Drosophila, experimental evolution, genetic architecture, learning, trade-off
National Category
Genetics
Identifiers
urn:nbn:se:uu:diva-320841 (URN)10.1111/evo.13156 (DOI)000396039000011 ()28000915 (PubMedID)
Funder
The Royal Swedish Academy of SciencesSwedish Research CouncilEU, European Research Council
Available from: 2017-04-26 Created: 2017-04-26 Last updated: 2017-09-07Bibliographically approved
Alavioon, G., Hotzy, C., Nakhro, K., Rudolf, S., Scofield, D., Zajitschek, S., . . . Immler, S. (2017). Haploid selection within a single ejaculate increases offspring fitness. Proceedings of the National Academy of Sciences of the United States of America (30), 8053-8058
Open this publication in new window or tab >>Haploid selection within a single ejaculate increases offspring fitness
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2017 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, no 30, p. 8053-8058Article in journal (Refereed) Published
Abstract [en]

An inescapable consequence of sex in eukaryotes is the evolution of a biphasic life cycle with alternating diploid and haploid phases. The occurrence of selection during the haploid phase can have far-reaching consequences for fundamental evolutionary processes including the rate of adaptation, the extent of inbreeding depression, and the load of deleterious mutations, as well as for applied research into fertilization technology. Although haploid selection is well established in plants, current dogma assumes that in animals, intact fertile sperm within a single ejaculate are equivalent at siring viable offspring. Using the zebrafish Danio rerio, we show that selection on phenotypic variation among intact fertile sperm within an ejaculate affects offspring fitness. Longer-lived sperm sired embryos with increased survival and a reduced number of apoptotic cells, and adult male offspring exhibited higher fitness. The effect on embryo viability was carried over into the second generation without further selection and was equally strong in both sexes. Sperm pools selected by motile phenotypes differed genetically at numerous sites throughout the genome. Our findings clearly link within-ejaculate variation in sperm phenotype to offspring fitness and sperm genotype in a vertebrate and have major implications for adaptive evolution.

National Category
Evolutionary Biology
Identifiers
urn:nbn:se:uu:diva-320335 (URN)10.1073/pnas.1705601114 (DOI)000406189900080 ()28698378 (PubMedID)
Funder
Swedish Research CouncilEU, European Research Council
Available from: 2017-04-19 Created: 2017-04-19 Last updated: 2018-05-07Bibliographically approved
Hooper, A. K., Spagopoulou, F., Wylde, Z., Maklakov, A. A. & Bonduriansky, R. (2017). Ontogenetic timing as a condition-dependent life history trait: High-condition males develop quickly, peak early, and age fast. Evolution, 71(3), 671-685
Open this publication in new window or tab >>Ontogenetic timing as a condition-dependent life history trait: High-condition males develop quickly, peak early, and age fast
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2017 (English)In: Evolution, ISSN 0014-3820, E-ISSN 1558-5646, Vol. 71, no 3, p. 671-685Article in journal (Refereed) Published
Abstract [en]

Within-population variation in ageing remains poorly understood. In males, condition-dependent investment in secondary sexual traits may incur costs that limit ability to invest in somatic maintenance. Moreover, males often express morphological and behavioral secondary sexual traits simultaneously, but the relative effects on ageing of investment in these traits remain unclear. We investigated the condition dependence of male life history in the neriid fly Telostylinus angusticollis. Using a fully factorial design, we manipulated male early-life condition by varying nutrient content of the larval diet and, subsequently, manipulated opportunity for adult males to interact with rival males. We found that high-condition males developed more quickly and reached their reproductive peak earlier in life, but also experienced faster reproductive ageing and died sooner than low-condition males. By contrast, interactions with rival males reduced male lifespan but did not affect male reproductive ageing. High-condition in early life is therefore associated with rapid ageing in T. angusticollis males, even in the absence of damaging male-male interactions. Our results show that abundant resources during the juvenile phase are used to expedite growth and development and enhance early-life reproductive performance at the expense of late-life performance and survival, demonstrating a clear link between male condition and ageing.

Place, publisher, year, edition, pages
WILEY, 2017
Keywords
Condition dependence, costs of secondary sexual traits, life history, reproductive ageing, senescence, sexual selection
National Category
Evolutionary Biology
Identifiers
urn:nbn:se:uu:diva-320842 (URN)10.1111/evo.13172 (DOI)000396039000012 ()28067402 (PubMedID)
Funder
Australian Research CouncilEU, European Research CouncilSwedish Research Council
Available from: 2017-04-26 Created: 2017-04-26 Last updated: 2018-04-09Bibliographically approved
Lind, M. I., Chen, H.-y., Cortazar-Chinarro, M. & Maklakov, A. A. (2017). Rapamycin additively extends lifespan in short- and long-lived lines of the nematode Caenorhabditis remanei. Experimental Gerontology, 90, 79-82
Open this publication in new window or tab >>Rapamycin additively extends lifespan in short- and long-lived lines of the nematode Caenorhabditis remanei
2017 (English)In: Experimental Gerontology, ISSN 0531-5565, E-ISSN 1873-6815, Vol. 90, p. 79-82Article in journal (Refereed) Published
Abstract [en]

Despite tremendous progress in finding genes that, when manipulated, affects lifespan, little is known about the genetics underlying natural variation in lifespan. While segregating genetic variants for lifespan has been notoriously difficult to find in genome-wide association studies (GWAS), a complementary approach is to manipulate key genetic pathways in lines that differ in lifespan. If these candidate pathways are down regulated in long-lived lines, these lines can be predicted to respond less to pharmaceutical down-regulation of these pathways than short-lived lines. Experimental studies have identified the nutrient-sensing pathway TOR as a key regulator of lifespan in model organisms, and this pathway can effectively be down regulated using the drug rapamycin, which extends lifespan in all tested species. We expose short-and long-lived lines of the nematode Caenorhabditis remanei to rapamycin, and investigate if long-lived lines, which are hypothesized to already have down-regulated TOR signaling, respond less to rapamycin. We found no interaction between line and rapamycin treatment, since rapamycin extended lifespan independent of the intrinsic lifespan of the lines. This shows that rapamycin is equally effective on long and short-lived lines, and suggests that the evolution of long life may involve more factors that down-regulation of TOR.

Keywords
Experimental evolution, Lifespan, Rapamycin, TOR
National Category
Biological Sciences
Research subject
Animal Ecology
Identifiers
urn:nbn:se:uu:diva-321343 (URN)10.1016/j.exger.2017.01.017 (DOI)000398012100010 ()28119053 (PubMedID)
Funder
Swedish Research CouncilEU, European Research Council
Available from: 2017-05-31 Created: 2017-05-31 Last updated: 2017-05-31Bibliographically approved
Lind, M. I., Chen, H.-y., Meurling, S., Guevara Gil, A. C., Carlsson, H., Zwoinska, M. K., . . . Maklakov, A. A. (2017). Slow development as an evolutionary cost of long life. Functional Ecology, 31(6), 1252-1261
Open this publication in new window or tab >>Slow development as an evolutionary cost of long life
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2017 (English)In: Functional Ecology, ISSN 0269-8463, E-ISSN 1365-2435, Vol. 31, no 6, p. 1252-1261Article in journal (Refereed) Published
Abstract [en]

Life-history theory predicts a trade-off between early-life fitness and life span. While the focus traditionally has been on the fecundity-life span trade-off, there are strong reasons to expect trade-offs with growth rate and/or development time. We investigated the roles of growth rate and development time in the evolution of life span in two independent selection experiments in the outcrossing nematode Caenorhabditis remanei. First, we found that selection under heat-shock leads to the evolution of increased life span without fecundity costs, but at the cost of slower development. Thereafter, the putative evolutionary links between development time, growth rate, fecundity, heat-shock resistance and life span were independently assessed in the second experiment by directly selecting for fast or slow development. This experiment confirmed our initial findings, since selection for slow development resulted in the evolution of long life span and increased heat-shock resistance. Because there were no consistent trade-offs with growth rate or fecundity, our results highlight the key role of development rate - differentiation of the somatic cells per unit of time - in the evolution of life span. Since development time is under strong selection in nature, reduced somatic maintenance resulting in shorter life span may be a widespread cost of rapid development.

Keywords
antagonistic pleiotropy, development time, growth, life span, stress resistance, trade-off
National Category
Ecology Zoology
Research subject
Biology
Identifiers
urn:nbn:se:uu:diva-232066 (URN)10.1111/1365-2435.12840 (DOI)000402642900009 ()
Funder
Swedish Research Council, 623-2012-6366EU, European Research Council
Available from: 2014-09-12 Created: 2014-09-12 Last updated: 2017-08-21Bibliographically approved
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