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Always a price to pay: hibernation at low temperatures comes with a trade-off between energy savings and telomere damage.

ABSTRACT: We experimentally tested the costs of deep torpor at low temperatures by comparing telomere dynamics in two species of rodents hibernating at either 3 or 14°C. Our data show that hibernators kept at the warmer temperature had higher arousal frequencies, but maintained longer telomeres than individuals hibernating at the colder temperature. We suggest that the high-energy demand of frequent arousals is counteracted by a lower temperature differential between torpid and euthermic body temperature and that telomere length is restored during arousals when the body temperature is returned to normothermic values. Taken together, our study shows that hibernation at low body temperatures comes with costs on a cellular level and that hibernators need to actively counterbalance the shortening of telomeres.

SUBMITTER: Nowack J

PROVIDER: S-EPMC6832184 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Always a price to pay: hibernation at low temperatures comes with a trade-off between energy savings and telomere damage.

Nowack Julia J Tarmann Iris I Hoelzl Franz F Smith Steve S Giroud Sylvain S Ruf Thomas T

Biology letters 20191002 10

We experimentally tested the costs of deep torpor at low temperatures by comparing telomere dynamics in two species of rodents hibernating at either 3 or 14°C. Our data show that hibernators kept at the warmer temperature had higher arousal frequencies, but maintained longer telomeres than individuals hibernating at the colder temperature. We suggest that the high-energy demand of frequent arousals is counteracted by a lower temperature differential between torpid and euthermic body temperature ...[more]

PMID: 31573426

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Project description:ImportanceAllowing the US Centers for Medicare & Medicaid Services to negotiate prescription drug prices for Medicare may improve drug affordability.ObjectiveTo estimate savings from Medicare price negotiation under the Inflation Reduction Act (IRA) and examine opportunities to increase savings.Design, setting, and participantsThis cross-sectional, population-based study used data from 2020 Medicare prescription drug claims. The study was conducted and data were analyzed in 2022.ExposuresEligibility for Medicare price negotiation under the IRA and alternative criteria.Main outcomes and measuresMinimum savings under the IRA's eligibility criteria were estimated and compared with savings within alternative scenarios, including (1) selecting drugs for negotiation based on net spending after rebates rather than gross spending; (2) extending eligibility to drugs with biosimilar or generic competitors; (3) reducing the minimum years since US Food and Drug Administration approval for eligibility; and (4) changing 2 or 3 of these factors. Estimated savings were calculated at different levels of scale-up of price negotiation under the IRA, from 10 Part D drugs in 2026 to 60 Part B and D drugs in 2029. Gross spending was calculated using the US Centers for Medicare & Medicaid Services 2020 Medicare drug spending dashboard. Rebates were estimated using SSR Health data. Information on FDA approvals, generics, and biosimilars was obtained from FDA websites.ResultsUnder IRA rules, estimated minimum savings from price negotiation in 2026 for 10 Part D drugs would be $3.2 billion. For 2029 for 60 Part D and B drugs, estimated savings were $16.0 billion. Selecting drugs for negotiation based on net rather than gross spending would be associated with estimated savings of $4.6 billion (a 45% increase) in 2026 and $18.9 billion (an 18% increase) in 2029. Including drugs with generic competitors or biosimilars would be associated with an estimated savings of $6.6 billion (a 109% increase) in 2026 and $24.9 billion (a 56% increase) in 2029. Making both changes would be associated with savings of $9.5 billion (a 200% increase) in 2026 and $28.3 billion (a 77% increase) in 2029. A sensitivity analysis suggested that reducing the required number of years since marketing approval by 2 years would be associated with increased estimated savings of 4% when 10 Part D drugs are negotiated and 12% when 60 Part D and B drugs are negotiated. Changing all 3 criteria would be associated with the greatest increase in estimated savings in 2029 (119% increase when 10 Part D drugs are negotiated and 93% increase for 60 Part D and B drugs).Conclusions and relevanceThe results of this cross-sectional study suggest that adjusting the eligibility criteria for Medicare prescription drug price negotiation to permit inclusion of drugs with biosimilar or generic competitors and selecting drugs based on net rather than gross spending may be a promising approach to substantially increase estimated savings.

Project description:IntroductionLife-history theory predicts that organisms trade off survival against reproduction. However, the time scales on which various consequences become evident and the physiology mediating the cost of reproduction remain poorly understood. Yet, explaining not only which mechanisms mediate this trade-off, but also how fast or slow the mechanisms act, is crucial for an improved understanding of life-history evolution. We investigated three time scales on which an experimental increase in body mass could affect this trade-off: within broods, within season and between years. We handicapped adult skylarks (Alauda arvensis) by attaching extra weight during first broods to both adults of a pair. We measured body mass, immune function and return rates in these birds. We also measured nest success, feeding rates, diet composition, nestling size, nestling immune function and recruitment rates.ResultsWhen nestlings of first broods fledged, parent body condition had not changed, but experimental birds experienced higher nest failure. Depending on the year, immune parameters of nestlings from experimental parents were either higher or lower than of control nestlings. Later, when parents were feeding their second brood, the balance between self-maintenance and nest success had shifted. Control and experimental adults differed in immune function, while mass and immune function of their nestlings did not differ. Although weights were removed after breeding, immune measurements during the second brood had the capacity to predict return rates to the next breeding season. Among birds that returned the next year, body condition and reproductive performance a year after the experiment did not differ between treatment groups.ConclusionsWe conclude that the balance between current reproduction and survival shifts from affecting nestlings to affecting parents as the reproductive season progresses. Furthermore, immune function is apparently one physiological mechanism involved in this trade-off. By unravelling a physiological mechanism underlying the trade-offs between current and future reproduction and by demonstrating the different time scales on which it acts, our study represents an important step in understanding a central theory of life-history evolution.

Dataset Information

Always a price to pay: hibernation at low temperatures comes with a trade-off between energy savings and telomere damage.

Publications

Always a price to pay: hibernation at low temperatures comes with a trade-off between energy savings and telomere damage.

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