Sex‐specific aging in animals: Perspective and future directions

Bronikowski, Anne M.; Meisel, Richard P.; Biga, Peggy R.; Walters, James R.; Mank, Judith E.; Larschan, Erica; Wilkinson, Gerald S.; Valenzuela, Nicole; Conard, Ashley Mae; Magalhães, João Pedro de; Duan, Jianan; Elias, Amy E.; Gamble, Tony; Graze, Rita M.; Gribble, Kristin E.; Kreiling, Jill A.; Riddle, Nicole C.

doi:10.1111/acel.13542

Cited by 53 publications

(34 citation statements)

References 280 publications

(350 reference statements)

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“…This sex difference in lifespan extension is likely independent of killifish social dynamics, as all animals were housed individually. Lifespan differences between sexes in response to DR is also observed in other species (Bronikowski et al, 2022). In mice, extreme DR (40%) extends lifespan in males, but not in females (Mitchell et al, 2016), though milder DR leads to a greater lifespan extension in females than males (Bonkowski et al, 2006;Kane et al, 2018;Mitchell et al, 2016).…”

Section: Discussionmentioning

confidence: 91%

An automated feeding system for the African killifish reveals effects of dietary restriction on lifespan and allows scalable assessment of associative learning

McKay

Chen

et al. 2021

Preprint

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The African turquoise killifish is an exciting new vertebrate model for aging studies. A significant challenge for any model organism is control over its diet in space and time. To address this challenge, we created an automated and networked fish feeding system. Our automated feeder is designed to be open-source, easily transferable, and built from widely available components. Compared to manual feeding, our automated system is highly precise and flexible. As a proof-of-concept for the feeding schedule flexibility of these automated feeders, we define a favorable regimen for growth and fertility for the African killifish and a dietary restriction regimen where both feeding time and quantity are reduced. We show that this dietary restriction regimen extends lifespan in males. Moreover, combining our automated feeding system with a video camera, we establish an associative learning assay for the killifish. This learning assay provides an integrative measure of cognitive decline during aging. The ability to precisely control food delivery in the killifish opens new areas to assess lifespan and cognitive behavior dynamics and to screen for dietary interventions and drugs in a high-throughput manner previously impossible with traditional vertebrate model organisms.

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Section: Discussionmentioning

confidence: 91%

An automated feeding system for the African killifish reveals effects of dietary restriction on lifespan and allows scalable assessment of associative learning

McKay

Chen

et al. 2021

Preprint

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“…Ageing as a trait shows strong sexual dimorphism in many species including mice ( Bronikowski et al, 2022 ) and man ( Hägg and Jylhävä, 2021 ). Unsurprisingly, both lifespan- ( Nadon et al, 2017 ) and healthspan-extending interventions ( Selman et al, 2009 ) frequently have sex-dependent efficacies.…”

Section: Discussionmentioning

confidence: 99%

Short senolytic or senostatic interventions rescue progression of radiation-induced frailty and premature ageing in mice

Fielder

Wan

Alimohammadiha

et al. 2022

eLife

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Cancer survivors suffer from progressive frailty, multimorbidity and premature morbidity. We hypothesize that therapy-induced senescence and senescence progression via bystander effects is a significant cause of this premature ageing phenotype. Accordingly, the study addresses the question whether a short anti-senescence intervention is able to block progression of radiation-induced frailty and disability in a pre-clinical setting. Male mice were sub-lethally irradiated at 5 months of age and treated (or not) with either a senolytic drug (Navitoclax or dasatinib + quercetin) for 10 days or with the senostatic metformin for 10 weeks. Follow up was for one year. Treatments commencing within a month after irradiation effectively reduced frailty progression (p<0.05) and improved muscle (p<0.01) and liver (p<0.05) function as well as short-term memory (p<0.05) until advanced age with no need for repeated interventions. Senolytic interventions that started late, after radiation-induced premature frailty was manifest, still had beneficial effects on frailty (p<0.05) and short-term memory (p<0.05). Metformin was similarly effective as senolytics. At therapeutically achievable concentrations metformin acted as a senostatic neither via inhibition of mitochondrial complex I, nor via improvement of mitophagy or mitochondrial function, but by reducing non-mitochondrial ROS production via NOX4 inhibition in senescent cells. Our study suggests that the progression of adverse long-term health and quality-of-life effects of radiation exposure, as experienced by cancer survivors, might be rescued by short-term adjuvant anti-senescence interventions.

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“…Understanding the mechanisms of immunosenescence could offer therapeutic potential in reducing age-associated morbidity ( Neves and Sousa-Victor, 2020 ; Borgoni et al, 2021 ). However, individuals do not age at the same rate, with variation arising from genotype ( Burger and Promislow, 2006 ; Belsky et al, 2015 ), including sex ( Sampathkumar et al, 2020 ; Xirocostas et al, 2020 ; Bronikowski et al, 2022 ), and from the environment. While most mechanistic biology research ignores this diversity, largely due to the practicality of using single genotypes and sexes, individual variation will determine the response to therapeutics targeting ageing pathologies ( Meyer et al, 2013 ; Fuselli, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Fly immunity comes of age: The utility of Drosophila as a model for studying variation in immunosenescence

Corbally

Regan

2022

Front. Aging

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The global demographic is shifting towards an aged population (United Nations, 2019). Yet, it is our oldest members of society that are the most vulnerable to infectious disease, reflecting immune system ageing, or "immunosenescence" (Glynn and Moss, 2020;Chen et al., 2021). Immunosenescence has two defining features: heightened susceptibility to pathogens, and increased systemic, basal inflammation (Franceschi, 2000;Zerofsky et al., 2005; Benayoun et al., 2019), which is strongly linked to the development of age-related diseases such as neurodegeneration and cancer (Franceschi

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Sex‐specific aging in animals: Perspective and future directions

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 53 publications

References 280 publications

An automated feeding system for the African killifish reveals effects of dietary restriction on lifespan and allows scalable assessment of associative learning

An automated feeding system for the African killifish reveals effects of dietary restriction on lifespan and allows scalable assessment of associative learning

Short senolytic or senostatic interventions rescue progression of radiation-induced frailty and premature ageing in mice

Fly immunity comes of age: The utility of Drosophila as a model for studying variation in immunosenescence

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