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Article ; Online: A Geroscience Perspective on COVID-19 Mortality.

Promislow, Daniel E L

The journals of gerontology. Series A, Biological sciences and medical sciences

2020 Volume 75, Issue 9, Page(s) e30–e33

Abstract: A novel coronavirus, SARS-CoV-2, emerged in December 2019, leading within a few months to a global pandemic. COVID-19, the disease caused by this highly contagious virus, can have serious health consequences, though risks of complications are highly age- ... ...

Abstract	A novel coronavirus, SARS-CoV-2, emerged in December 2019, leading within a few months to a global pandemic. COVID-19, the disease caused by this highly contagious virus, can have serious health consequences, though risks of complications are highly age-dependent. Rates of hospitalization and death are less than 0.1% in children, but increase to 10% or more in older people. Moreover, at all ages, men are more likely than women to suffer serious consequences from COVID-19. These patterns are familiar to the geroscience community. The effects of age and sex on mortality rates from COVID-19 mirror the effects of aging on almost all major causes of mortality. These similarities are explored here, and underscore the need to consider the role of basic biological mechanisms of aging on potential treatment and outcomes of COVID-19.
MeSH term(s)	Aged ; Aging/physiology ; Betacoronavirus ; COVID-19 ; Cause of Death ; Comorbidity ; Coronavirus Infections/immunology ; Coronavirus Infections/mortality ; Female ; Hospitalization/statistics & numerical data ; Humans ; Life Expectancy ; Male ; Mortality ; Pandemics/statistics & numerical data ; Pneumonia, Viral/immunology ; Pneumonia, Viral/mortality ; Risk Factors ; SARS-CoV-2 ; Sex Factors
Keywords	covid19
Language	English
Publishing date	2020-04-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1223643-3
ISSN	1758-535X ; 1079-5006
ISSN (online)	1758-535X
ISSN	1079-5006
DOI	10.1093/gerona/glaa094
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Article ; Online: A New Concept in Diet Restriction Is Cleaning Up!

Promislow, Daniel E L

The journals of gerontology. Series A, Biological sciences and medical sciences

2020 Volume 76, Issue 4, Page(s) 599–600

MeSH term(s)	Bibliographies as Topic ; Caloric Restriction ; Healthy Aging/physiology ; Humans ; Life Expectancy ; Longevity/physiology
Language	English
Publishing date	2020-08-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1223643-3
ISSN	1758-535X ; 1079-5006
ISSN (online)	1758-535X
ISSN	1079-5006
DOI	10.1093/gerona/glaa195
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Article ; Online: Cellular age explains variation in age-related cell-to-cell transcriptome variability.

Yang, Ming / Harrison, Benjamin R / Promislow, Daniel E L

Genome research

2023

Abstract: Organs and tissues age at different rates within a single individual. Such asynchrony in aging has been widely observed at multiple levels, from functional hallmarks, such as anatomical structures and physiological processes, to molecular endophenotypes, ...

Abstract	Organs and tissues age at different rates within a single individual. Such asynchrony in aging has been widely observed at multiple levels, from functional hallmarks, such as anatomical structures and physiological processes, to molecular endophenotypes, such as the transcriptome and metabolome. However, we lack a conceptual framework to understand why some components age faster than others. Just as demographic models explain why aging evolves, here we test the hypothesis that demographic differences among cell types, determined by cell-specific differences in turnover rate, can explain why the transcriptome shows signs of aging in some cell types but not others. Through analysis of mouse single-cell transcriptome data across diverse tissues and ages, we find that cellular age explains a large proportion of the variation in the age-related increase in transcriptome variance. We further show that long-lived cells are characterized by relatively high expression of genes associated with proteostasis and that the transcriptome of long-lived cells shows greater evolutionary constraint than short-lived cells. In contrast, in short-lived cell types, the transcriptome is enriched for genes associated with DNA repair. Based on these observations, we develop a novel heuristic model that explains how and why aging rates differ among cell types.
Language	English
Publishing date	2023-11-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	1284872-4
ISSN	1549-5469 ; 1088-9051 ; 1054-9803
ISSN (online)	1549-5469
ISSN	1088-9051 ; 1054-9803
DOI	10.1101/gr.278144.123
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Article ; Online: In search of a Drosophila core cellular network with single-cell transcriptome data.

Yang, Ming / Harrison, Benjamin R / Promislow, Daniel E L

G3 (Bethesda, Md.)

2022 Volume 12, Issue 10

Abstract: Along with specialized functions, cells of multicellular organisms also perform essential functions common to most if not all cells. Whether diverse cells do this by using the same set of genes, interacting in a fixed coordinated fashion to execute ... ...

Abstract	Along with specialized functions, cells of multicellular organisms also perform essential functions common to most if not all cells. Whether diverse cells do this by using the same set of genes, interacting in a fixed coordinated fashion to execute essential functions, or a subset of genes specific to certain cells, remains a central question in biology. Here, we focus on gene coexpression to search for a core cellular network across a whole organism. Single-cell RNA-sequencing measures gene expression of individual cells, enabling researchers to discover gene expression patterns that contribute to the diversity of cell functions. Current efforts to study cellular functions focus primarily on identifying differentially expressed genes across cells. However, patterns of coexpression between genes are probably more indicative of biological processes than are the expression of individual genes. We constructed cell-type-specific gene coexpression networks using single-cell transcriptome datasets covering diverse cell types from the fruit fly, Drosophila melanogaster. We detected a set of highly coordinated genes preserved across cell types and present this as the best estimate of a core cellular network. This core is very small compared with cell-type-specific gene coexpression networks and shows dense connectivity. Gene members of this core tend to be ancient genes and are enriched for those encoding ribosomal proteins. Overall, we find evidence for a core cellular network in diverse cell types of the fruit fly. The topological, structural, functional, and evolutionary properties of this core indicate that it accounts for only a minority of essential functions.
MeSH term(s)	Animals ; Drosophila/genetics ; Drosophila melanogaster/genetics ; Gene Expression Profiling ; Gene Regulatory Networks ; RNA ; Ribosomal Proteins/genetics ; Transcriptome
Chemical Substances	Ribosomal Proteins ; RNA (63231-63-0)
Language	English
Publishing date	2022-08-17
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2629978-1
ISSN	2160-1836 ; 2160-1836
ISSN (online)	2160-1836
ISSN	2160-1836
DOI	10.1093/g3journal/jkac212
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Article: Demographic factors associated with joint supplement use in dogs from the Dog Aging Project.

Hoffman, Jessica M / Tolbert, M Katherine / Promislow, Daniel E L

Frontiers in veterinary science

2022 Volume 9, Page(s) 906521

Abstract: Osteoarthritis (OA) is one of the most prevalent age-related chronic conditions that afflict companion dogs, and multiple joint supplements are available to prevent or treat OA, though the efficacy of these treatments is controversial. While the ... ...

Abstract	Osteoarthritis (OA) is one of the most prevalent age-related chronic conditions that afflict companion dogs, and multiple joint supplements are available to prevent or treat OA, though the efficacy of these treatments is controversial. While the demographic factors that are associated with OA diagnosis are well established, the factors that are associated with joint supplement use are not as well studied. Using data collected from the Dog Aging Project, we analyzed owner survey responses regarding joint supplement administration and OA diagnosis for 26,951 adult dogs. In this cross-sectional analysis, logistic regression models and odds-ratios (OR) were employed to determine demographic factors of dogs and their owners that were associated with joint supplement administration. Forty percent of adult dogs in our population were given some type of joint supplement. Perhaps not surprisingly, dogs of older age, larger size, and those that were ever overweight were more likely to receive a joint supplement. Younger owner age, urban living, owner education, and feeding commercial dry food were associated with a reduced likelihood of administration of joint supplements to dogs. Interestingly, mixed breed dogs were also less likely to be administered a joint supplement (OR: 0.73). Dogs with a clinical diagnosis of OA were more likely to receive a joint supplement than those without a reported OA diagnosis (OR: 3.82). Neutered dogs were more likely to have a diagnosis of OA, even after controlling for other demographic factors, yet their prevalence of joint supplement administration was the same as intact dogs. Overall, joint supplement use appears to be high in our large population of dogs in the United States. Prospective studies are needed to determine if joint supplements are more commonly administered as a preventative for OA or after an OA clinical diagnosis.
Language	English
Publishing date	2022-07-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2834243-4
ISSN	2297-1769
ISSN	2297-1769
DOI	10.3389/fvets.2022.906521
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Article ; Online: How size and genetic diversity shape lifespan across breeds of purebred dogs.

Kraus, Cornelia / Snyder-Mackler, Noah / Promislow, Daniel E L

GeroScience

2022 Volume 45, Issue 2, Page(s) 627–643

Abstract: While the lifespan advantage of small body size and mixed breed status has been documented repeatedly, evidence for an effect of genetic diversity across dog breeds is equivocal. We hypothesized that this might be due to a strong right-censoring bias in ... ...

Abstract	While the lifespan advantage of small body size and mixed breed status has been documented repeatedly, evidence for an effect of genetic diversity across dog breeds is equivocal. We hypothesized that this might be due to a strong right-censoring bias in available breed-specific lifespan estimates where early-dying dogs from birth cohorts that have not died off completely at the time of data collection are sampled disproportionately, especially in breeds with rapidly growing populations. We took advantage of data on owner reported lifespan and cause of death from a large public database to quantify the effect of size and genetic diversity (heterozygosity) on mortality patterns across 118 breeds based on more than 40,000 dogs. After documenting and removing the right-censoring bias from the breed-specific lifespan estimates by including only completed birth cohorts in our analyses, we show that small size and genetic diversity are both linked to a significant increase in mean lifespan across breeds. To better understand the proximate mechanisms underlying these patterns, we then investigated two major mortality causes in dogs - the cumulative pathophysiologies of old age and cancer. Old age lifespan, as well as the percentage of old age mortality, decreased with increasing body size and increased with increasing genetic diversity. The lifespan of dogs dying of cancer followed the same patterns, but while large size significantly increased proportional cancer mortality, we could not detect a significant signal for lowered cancer mortality with increasing diversity. Our findings suggest that outcross programs will be beneficial for breed health and longevity. They also emphasize the need for high-quality mortality data for veterinary epidemiology as well as for developing the dog as a translational model for human geroscience.
MeSH term(s)	Humans ; Dogs ; Animals ; Longevity/genetics ; Genetic Variation ; Neoplasms
Language	English
Publishing date	2022-09-06
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2886586-8
ISSN	2509-2723 ; 2509-2715
ISSN (online)	2509-2723
ISSN	2509-2715
DOI	10.1007/s11357-022-00653-w
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Article ; Online: A Geroscience Perspective on COVID-19 Mortality

Promislow, Daniel E L

The Journals of Gerontology: Series A

2020 Volume 75, Issue 9, Page(s) e30–e33

Abstract: Abstract A novel coronavirus, SARS-CoV-2, emerged in December 2019, leading within a few months to a global pandemic. COVID-19, the disease caused by this highly contagious virus, can have serious health consequences, though risks of complications are ... ...

Abstract	Abstract A novel coronavirus, SARS-CoV-2, emerged in December 2019, leading within a few months to a global pandemic. COVID-19, the disease caused by this highly contagious virus, can have serious health consequences, though risks of complications are highly age-dependent. Rates of hospitalization and death are less than 0.1% in children, but increase to 10% or more in older people. Moreover, at all ages, men are more likely than women to suffer serious consequences from COVID-19. These patterns are familiar to the geroscience community. The effects of age and sex on mortality rates from COVID-19 mirror the effects of aging on almost all major causes of mortality. These similarities are explored here, and underscore the need to consider the role of basic biological mechanisms of aging on potential treatment and outcomes of COVID-19.
Keywords	Ageing ; Geriatrics and Gerontology ; covid19
Language	English
Publisher	Oxford University Press (OUP)
Publishing country	uk
Document type	Article ; Online
ZDB-ID	1223643-3
ISSN	1758-535X ; 1079-5006
ISSN (online)	1758-535X
ISSN	1079-5006
DOI	10.1093/gerona/glaa094
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: A Geroscience Perspective on COVID-19 Mortality

Promislow, Daniel E L

J Gerontol A Biol Sci Med Sci

Abstract	A novel coronavirus, SARS-CoV-2, emerged in December 2019, leading within a few months to a global pandemic. COVID-19, the disease caused by this highly contagious virus, can have serious health consequences, though risks of complications are highly age-dependent. Rates of hospitalization and death are less than 0.1% in children, but increase to 10% or more in older people. Moreover, at all ages, men are more likely than women to suffer serious consequences from COVID-19. These patterns are familiar to the geroscience community. The effects of age and sex on mortality rates from COVID-19 mirror the effects of aging on almost all major causes of mortality. These similarities are explored here, and underscore the need to consider the role of basic biological mechanisms of aging on potential treatment and outcomes of COVID-19.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #72050
Database	COVID19

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Article ; Online: The Biology of Aging in Insects: From

Promislow, Daniel E L / Flatt, Thomas / Bonduriansky, Russell

Annual review of entomology

2021 Volume 67, Page(s) 83–103

Abstract: An enormous amount of work has been done on aging ... ...

Abstract	An enormous amount of work has been done on aging in
MeSH term(s)	Aging ; Animals ; Drosophila melanogaster/physiology ; Insecta/physiology
Language	English
Publishing date	2021-09-30
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	207927-6
ISSN	1545-4487 ; 0066-4170
ISSN (online)	1545-4487
ISSN	0066-4170
DOI	10.1146/annurev-ento-061621-064341
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Article ; Online: Serotonin signaling modulates aging-associated metabolic network integrity in response to nutrient choice in Drosophila melanogaster.

Lyu, Yang / Promislow, Daniel E L / Pletcher, Scott D

Communications biology

2021 Volume 4, Issue 1, Page(s) 740

Abstract: Aging arises from complex interactions among multiple biochemical products. Systems-level analyses of biological networks may provide insights into the causes and consequences of aging that evade single-gene studies. We have previously found that dietary ...

Abstract	Aging arises from complex interactions among multiple biochemical products. Systems-level analyses of biological networks may provide insights into the causes and consequences of aging that evade single-gene studies. We have previously found that dietary choice is sufficient to modulate aging in the vinegar fly, Drosophila melanogaster. Here we show that nutrient choice influenced several measures of metabolic network integrity, including connectivity, community structure, and robustness. Importantly, these effects are mediated by serotonin signaling, as a mutation in serotonin receptor 2A (5-HT2A) eliminated the effects of nutrient choice. Changes in network structure were associated with organism resilience and increased susceptibility to genetic perturbation. Our data suggest that the behavioral or perceptual consequences of exposure to individual macronutrients, involving serotonin signaling through 5-HT2A, qualitatively change the state of metabolic networks throughout the organism from one that is highly connected and robust to one that is fragmented, fragile, and vulnerable to perturbations.
MeSH term(s)	Aging/physiology ; Animals ; Drosophila melanogaster/metabolism ; Feeding Behavior/physiology ; Longevity/physiology ; Male ; Metabolic Networks and Pathways/physiology ; Metabolomics ; Nutrients ; Receptor, Serotonin, 5-HT2A/genetics ; Receptor, Serotonin, 5-HT2A/metabolism ; Serotonin/metabolism ; Signal Transduction/physiology
Chemical Substances	Receptor, Serotonin, 5-HT2A ; Serotonin (333DO1RDJY)
Language	English
Publishing date	2021-06-15
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	2399-3642
ISSN (online)	2399-3642
DOI	10.1038/s42003-021-02260-5
Database	MEDical Literature Analysis and Retrieval System OnLINE

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