Madison Ueland

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on the atlas · 69

highlights · 189

many age-related increases in individual RE transcripts could be fit to an exponential pattern
Repetitive elements as a transcriptomic marker of aging: Evidence in multiple datasets and models - LaRocca - 2020 - Aging Cell
analyses of RE in RNA-seq data are inherently challenging and artifact-prone because of the many RE copies and their various locations in the genome.
Repetitive elements as a transcriptomic marker of aging: Evidence in multiple datasets and models - LaRocca - 2020 - Aging Cell
raises the question of whether TE expression is simply a by-product of age-related heterochromatin breakdown or whether TE themselves can contribute to the aging process
Artificially stimulating retrotransposon activity increases mortality and accelerates a subset of aging phenotypes in Drosophila | eLife
raises the question of whether TE expression is simply a by-product of age-related heterochromatin breakdown or whether TE themselves can contribute to the aging process
Artificially stimulating retrotransposon activity increases mortality and accelerates a subset of aging phenotypes in Drosophila | eLife
examine the impact of growth media and other culture conditions on cell viability
A Call for Context (in Cell Culture) - New Science
His work offers a template for examining how emergent properties arise from individual parts. When we isolate cells and grow them in culture, we miss these emergent properties entirely.
A Call for Context (in Cell Culture) - New Science
how can we understand the factors that inform a cell’s identity from first principles?
A Call for Context (in Cell Culture) - New Science
I turned to a nascent field called cell systems, which is about understanding how changes in a cell’s multicellular context can shape its behavior; a bottom-up approach.
A Call for Context (in Cell Culture) - New Science
There are also neonatal cancers that don’t require medical intervention because they are expected to spontaneously regress.
A Call for Context (in Cell Culture) - New Science
Some proteins are notoriously difficult to study in vitro. Membrane proteins are picky about their chemical environment, and so-called ‘intrinsically disordered’ proteins are doomed to carry this misnomer only because we lack sufficient understanding of their binding interactions, however weak and transient.
Measure Proteins in Place - New Science
Structures are important on their own, but the secrets of protein folding cannot be understood without accounting for the conditions, environment, and molecular chaperones within a cell.
Measure Proteins in Place - New Science
I do think it is still possible to find a combined intervention that mimmicks what reprogramming does.
Nintil - Aging is already solved in vitro. What comes next?
there is no rejuvenation without fixing the epigenome
Nintil - Aging is already solved in vitro. What comes next?
If cells can select healthy ones and selectively replace damaged mitochondria with new ones, and if reprogramming favors this process we may not need to do anything about mitochondria that reprogramming is not fixing already, with the possible exception of so called rho-0 cells where all mitochondria are dysfunctional.
Nintil - Aging is already solved in vitro. What comes next?
Fixing cellular aging then leaves non-cellular forms of damage that would also need to be repaired. I don't know of any comprehensive catalogue of these, but off the top of my head we need to address as well:
Nintil - Aging is already solved in vitro. What comes next?
We don't yet know for sure if this is true, no one has looked at, for example, whether cells can get rid of lipofuscin when reprogrammed, but we do know that given a drug cells can be coaxed into it
Nintil - Aging is already solved in vitro. What comes next?
While there may not yet be an established link between AMH and markers of longevity, the question is timely and urgent: can markers of ovarian aging predict lifespan? If the age of menopause can be predicted, can it be modified? If the age of menopause can be modified, can lifespan—and most importantly health span—be modified?
The quest for biomarkers linking ovarian aging and longevity - Fertility and Sterility
Sense codons are commonly more abundant than stop codons by several orders of magnitude, and—in principle—high-fidelity genome synthesis would be the preferred route for tackling their removal.
Total synthesis of Escherichia coli with a recoded genome - PMC
synonymous codon compression
Total synthesis of Escherichia coli with a recoded genome - PMC
Synonymous codon choice has diverse and important roles, and many synonymous substitutions are detrimental. Here we demonstrate that the number of codons used to encode the canonical amino acids can be reduced, through the genome-wide substitution of target codons by defined synonyms.
Total synthesis of Escherichia coli with a recoded genome - PMC
The combination of genome recoding and codon reassignment might provide a universal strategy to make any species resistant to all natural viruses.
Swapped genetic code blocks viral infections and gene transfer | bioRxiv
We hypothesize that bacteriophages that rely on the fewest number of TCR codons to express essential proteins, e.g., Escherichia phage EC6098 with only 33 TCR positions in its six protein-coding genes38, have the highest potential to overcome an amino-acid-swapped code.
Swapped genetic code blocks viral infections and gene transfer | bioRxiv
the selection pressure posed by the altered genetic codes of GROs might facilitate the rapid evolution of viruses and mobile genetic elements capable of crossing a genetic-code-based barrier
Swapped genetic code blocks viral infections and gene transfer | bioRxiv
This amino-acid-swapped genetic code renders cells completely resistant to viral infections by mistranslating viral proteomes and prevents the escape of synthetic genetic information by engineered reliance on serine codons to produce leucine-requiring proteins.
Swapped genetic code blocks viral infections and gene transfer | bioRxiv
Arguably, if more resources are available, then organisms should invest more, not less, in somatic maintenance, in which case DR ought to shorten life span
Genetics of Longevity in Model Organisms: Debates and Paradigm Shifts | Annual Review of Physiology
A critical test of this theory is whether enhancement of xenobiotic metabolism is sufficient to extend life span
Genetics of Longevity in Model Organisms: Debates and Paradigm Shifts | Annual Review of Physiology
Is it caused by accumulation of damage and, if so, by what kind of damage? Are the oxygen and other reactive molecules postulated as key to aging by the free radical theory really of paramount importance, or are other kinds of damage to macromolecules as or more important? For instance, do endogenously or exogenously generated toxins build up in cells during aging? Or is the key to aging damage to levels of organization other than that of macromolecules—for instance, the level of chromosomes, mitochondria, cell membranes, the extracellular matrix, or the systemic environment? Is aging caused b…
Genetics of Longevity in Model Organisms: Debates and Paradigm Shifts | Annual Review of Physiology
including but not limited to metformin, rapamycin and CR
Study of Longitudinal Aging in Mice: Presentation of Experimental Techniques | The Journals of Gerontology: Series A | Oxford Academic
initiated a longitudinal intervention study that builds on the baseline SLAM study, where small molecules and dietary interventions are being tested as effective means to prevent and/or mitigate aging and age-associated phenotypes.
Study of Longitudinal Aging in Mice: Presentation of Experimental Techniques | The Journals of Gerontology: Series A | Oxford Academic
One of the primary goals of the SLAM study is to determine whether the trajectories of change driving the aging phenotypes in mice differ from those in humans in BLSA, and to identify factors that are reliable predictors and/or drivers of aging across species
Study of Longitudinal Aging in Mice: Presentation of Experimental Techniques | The Journals of Gerontology: Series A | Oxford Academic
The good news is that this steep rise in mortality should be accompanied by a steep rise in heritability, implying that conscious attention to both alleles and environments should enable significant enhancement of healthspan.
Genetic Cartography of Longevity in Humans and Mice: Current Landscape and Horizons - PMC
Age at menopause, the best metric of reproductive aging in humans, has a heritability that is significantly higher—about 60–65%
Genetic Cartography of Longevity in Humans and Mice: Current Landscape and Horizons - PMC
GWAS have high mapping precision but low power (hence the need for large sample sizes), while studies using rodents generally have modest mapping precision (1 to 10 Mb) but relatively high power. By combining results from both, we can gain both power and precision to detect gene variants associated with longevity—an approach that has been highly effective in other areas of research
Genetic Cartography of Longevity in Humans and Mice: Current Landscape and Horizons - PMC
the paucity of longevity hits is primarily the result of inadequate sample size rather than a fundamental problem related to genetic control (or lack thereof) of lifespan
Genetic Cartography of Longevity in Humans and Mice: Current Landscape and Horizons - PMC
These candidate gene studies often test for enrichment of specific alleles in old cohorts [27, 33]. While this approach may eventually fulfill its promise, hypothesis-driven tests of longevity linked gene variants have generally failed to replicate
Genetic Cartography of Longevity in Humans and Mice: Current Landscape and Horizons - PMC
such interventions often do not have to be deployed until relatively late in life—after reproduction is finished
Is antagonistic pleiotropy ubiquitous in aging biology? | Evolution, Medicine, and Public Health | Oxford Academic
Whenever an allele or new mutation is discovered to extend life, some detrimental effect on early life fitness is almost always observed. This explains why longevity alleles are not favored in wild populations.
Is antagonistic pleiotropy ubiquitous in aging biology? | Evolution, Medicine, and Public Health | Oxford Academic
In house mice (Mus musculus), neither field studies nor focused long-term laboratory selection studies—the preferred ways to evaluate evolutionary hypotheses—have been purposefully done.
Is antagonistic pleiotropy ubiquitous in aging biology? | Evolution, Medicine, and Public Health | Oxford Academic
antagonistic pleiotropy trade-offs between larval growth and longevity, not reproduction and longevity, emphasizing the fact that there are multiple important components of early life fitness
Is antagonistic pleiotropy ubiquitous in aging biology? | Evolution, Medicine, and Public Health | Oxford Academic
Experimental evolution of selected lines and hybrids suggest that antagonistic pleiotropy rather than Medawar’s mutation accumulation is the major genetic mechanism driving late life mortality in flies
Is antagonistic pleiotropy ubiquitous in aging biology? | Evolution, Medicine, and Public Health | Oxford Academic
The discovery of antagonistic pleiotropy in the laboratory has occurred by either (i) direct selection experiments for long life or (ii) partial or full inactivation of a gene leads to a significant increase in lifespan; however, when investigated further, this alteration has had a deleterious effect on some component of early life fitness
Is antagonistic pleiotropy ubiquitous in aging biology? | Evolution, Medicine, and Public Health | Oxford Academic
these trade-offs are often absent among captive mammals and birds, suggesting that the selective pressures that drive antagonistic pleiotropy are relaxed under the benign environmental conditions
Is antagonistic pleiotropy ubiquitous in aging biology? | Evolution, Medicine, and Public Health | Oxford Academic
Note that such trade-offs are consistent with the hypothesis of antagonistic pleiotropy, but because the genetic bases of trade-offs in natural populations are typically unknown, they cannot be cleanly attributed to that mechanism.
Is antagonistic pleiotropy ubiquitous in aging biology? | Evolution, Medicine, and Public Health | Oxford Academic
although antagonistic pleiotropic effects (i.e. trade-offs in reproduction and longevity) have been posited in humans, there are no compelling cases where the underlying gene or allele responsible for the trade-off has been identified.
Is antagonistic pleiotropy ubiquitous in aging biology? | Evolution, Medicine, and Public Health | Oxford Academic
Evolutionary hypotheses can be informatively tested in the laboratory by imposing experimental evolution paradigms.
Is antagonistic pleiotropy ubiquitous in aging biology? | Evolution, Medicine, and Public Health | Oxford Academic
The long-lived mutant disappears within a handful of generations due to a small, previously unnoticed, reduction in early life fertility
Is antagonistic pleiotropy ubiquitous in aging biology? | Evolution, Medicine, and Public Health | Oxford Academic
these two potential evolutionary mechanism of aging are not mutually exclusive
Is antagonistic pleiotropy ubiquitous in aging biology? | Evolution, Medicine, and Public Health | Oxford Academic
mutation accumulation or antagonistic pleiotropy
Is antagonistic pleiotropy ubiquitous in aging biology? | Evolution, Medicine, and Public Health | Oxford Academic
modern use of model organisms to understand aging in general actually presupposes antagonistic pleiotropy
Is antagonistic pleiotropy ubiquitous in aging biology? | Evolution, Medicine, and Public Health | Oxford Academic
If on the other hand, we assume that a limited number of biological processes have the rather strange characteristic that they can be beneficial early in life yet detrimental later on, then Williams’ hypothesis of antagonistic pleiotropy suggests that many mechanisms of aging may be conserved across species.
Is antagonistic pleiotropy ubiquitous in aging biology? | Evolution, Medicine, and Public Health | Oxford Academic