Testing the evidence that lifespan-extending compound interventions are conserved across laboratory animal model species

Bene, Michael; Salmon, Adam B.

doi:10.1007/s11357-022-00722-0

Cited by 4 publications

(4 citation statements)

References 64 publications

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“…A triad consisted of 1 day of FR1 session, then the next day FR2, and the third day again an FR1 session. FR2 was a modified version of the original task (FR1) with increased task difficulty: The first simultaneous nose-poke did not result in a reward but only in an “acknowledging” tone stimulus, and right after, a further simultaneous nose-poke (within 1 s) was required to get the reward [ 4 ]. In the first two sessions, respectively 6 and 4 pairs were “mixed” BPAP-saline pairs (i.e.…”

Section: Methodsmentioning

confidence: 99%

“…The reasons behind the serial failures of novel drug candidates are manifold, but the low predictive power of the applied animal models is certainly a major one. Regarding aging models, the relative short duration of the studies using either accelerated aging models or species of much shorter lifespan than that of man constitutes a major translational problem [ 4 – 6 ], while in area of age-related diseases, the not enough prudent reliance on hypothesized disease pathomechanism (see the case of amyloid theory in Alzheimer’s disease) and the overwhelming and uncritical use of transgenic mouse models are mostly blamed for the failures [ 1 , 5 , 7 , 8 ]. The (over)simplified cognitive defect paradigms form a common flaw of both fields [ 1 , 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

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Age-related decline of various cognitive functions in well-experienced male rats treated with the putative anti-aging compound (2R)-1-(1-benzofuran-2-yl)-N-propylpentane-2-amine ((-)BPAP)

Ernyey,

Kassai,

Kozma

et al. 2023

GeroScience

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Aging-associated cognitive disorders lack proper medication. To meet this need translation-wise, modification of the animal models is also required. In the present study, effect of the putative anti-aging compound (2R)-1-(1-benzofuran-2-yl)-N-propylpentane-2-amine ((-)BPAP, a deprenyl derivative) on age-related cognitive decline was investigated in experienced, aged Long-Evans rats. During their lifetime, animals had acquired knowledge in various cognitive assays. Their performance in these tests was then parallel followed from the age of 27 months until their death meanwhile half of them were treated with BPAP. Cognitive performance in various tasks showed different sensitivities/resistances to age-related impairment. Pot jumping performance (motor skill-learning) started to impair first, at 21 months of age, followed by decreasing performance in five-choice serial reaction time task (attention) at 26 months. Navigation performance in Morris water maze (spatial learning) started to decline at 31 months. Performance in a cooperation task (social cognition) started to decline the latest, at 34 months. Our findings suggest that in this process, the primary factor was the level of motivation to be engaged with the task and not losing the acquired knowledge. The average lifespan of the tested rat population was 36 months. BPAP could not improve the cognitive performance; neither could it prolong lifespan. A possible reason might be that dietary restriction and lifelong cognitive engagement had beneficial effects on cognitive capabilities and lifespan creating a “ceiling effect” for further improvement. The results confirmed that experienced animals provide a translationally relevant model to study age-related cognitive decline and measure the effect of putative anti-aging compounds.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Age-related decline of various cognitive functions in well-experienced male rats treated with the putative anti-aging compound (2R)-1-(1-benzofuran-2-yl)-N-propylpentane-2-amine ((-)BPAP)

Ernyey,

Kassai,

Kozma

et al. 2023

GeroScience

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“…However, there is a significant gap in the physiology between non‐mammalian model organisms or cells and complex in vivo human tissues and organs, with respect to architecture and function. The pitfalls of translating between non‐mammalian and mammalian aging models are underscored by a recent review demonstrating that the life‐extending effects of compounds in C. elegans and D. melanogaster are inconsistently conserved in mouse models (Bene & Salmon, 2023 ).…”

Section: Microphysiological Systems For Studying Aging Phenotypes And...mentioning

confidence: 99%

Microphysiological systems for human aging research

Park,

Laskow,

Chen

et al. 2024

Aging Cell

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Recent advances in microphysiological systems (MPS), also known as organs‐on‐a‐chip (OoC), enable the recapitulation of more complex organ and tissue functions on a smaller scale in vitro. MPS therefore provide the potential to better understand human diseases and physiology. To date, numerous MPS platforms have been developed for various tissues and organs, including the heart, liver, kidney, blood vessels, muscle, and adipose tissue. However, only a few studies have explored using MPS platforms to unravel the effects of aging on human physiology and the pathogenesis of age‐related diseases. Age is one of the risk factors for many diseases, and enormous interest has been devoted to aging research. As such, a human MPS aging model could provide a more predictive tool to understand the molecular and cellular mechanisms underlying human aging and age‐related diseases. These models can also be used to evaluate preclinical drugs for age‐related diseases and translate them into clinical settings. Here, we provide a review on the application of MPS in aging research. First, we offer an overview of the molecular, cellular, and physiological changes with age in several tissues or organs. Next, we discuss previous aging models and the current state of MPS for studying human aging and age‐related conditions. Lastly, we address the limitations of current MPS and present future directions on the potential of MPS platforms for human aging research.

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“…While caloric restriction has been reported to extend the lifespan [ 25 , 26 ], substances that extend the lifespan have also been reported. Extensive research by numerous investigators is underway to explore substances that extend the lifespan of mice [ 27 , 28 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

Oral Administration of Nacre Extract from Pearl Oyster Shells Has Anti-Aging Effects on Skin and Muscle, and Extends the Lifespan in SAMP8 Mice

Yamamoto,

Shimomura,

Hasegawa

2024

Pharmaceuticals

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Pearl oysters have been extensively utilized in pearl production; however, most pearl oyster shells are discarded as industrial waste. In a previous study, we demonstrated that the intraperitoneal administration of pearl oyster shell-derived nacre extract (NE) prevented d-galactose-induced brain and skin aging. In this study, we examined the anti-aging effects of orally administered NE in senescence-accelerated mice (SAMP8). Feeding SAMP8 mice NE prevented the development of aging-related characteristics, such as coarse and dull hair, which are commonly observed in aged mice. Additionally, the NE mitigated muscle aging in SAMP8 mice, such as a decline in grip strength. Histological analysis of skeletal muscle revealed that the NE suppressed the expression of aging markers, cyclin-dependent kinase inhibitor 2A (p16) and cyclin-dependent kinase inhibitor 1 (p21), and increased the expression of sirtuin1 and peroxisome proliferator-activated receptor gamma coactivator 1 (PGC1)- α, which are involved in muscle synthesis. These findings suggest that the oral administration of NE suppresses skeletal muscle aging. Moreover, NE administration suppressed skin aging, including a decline in water content. Interestingly, oral administration of NE significantly extended the lifespan of SAMP8 mice, suggesting that its effectiveness as an anti-aging agent of various tissues including skeletal muscle, skin, and adipose tissue.

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Testing the evidence that lifespan-extending compound interventions are conserved across laboratory animal model species

Cited by 4 publications

References 64 publications

Age-related decline of various cognitive functions in well-experienced male rats treated with the putative anti-aging compound (2R)-1-(1-benzofuran-2-yl)-N-propylpentane-2-amine ((-)BPAP)

Age-related decline of various cognitive functions in well-experienced male rats treated with the putative anti-aging compound (2R)-1-(1-benzofuran-2-yl)-N-propylpentane-2-amine ((-)BPAP)

Microphysiological systems for human aging research

Oral Administration of Nacre Extract from Pearl Oyster Shells Has Anti-Aging Effects on Skin and Muscle, and Extends the Lifespan in SAMP8 Mice

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