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DOE OSTI2025

Chromosome duplication causes premature aging via defects in ribosome quality control

Down syndrome, caused by an extra copy of Chromosome 21, causes lifelong problems. One of the most common phenotypes among people with Down syndrome is premature aging, including early tissue decline, neurodegeneration, and shortened life span. Yet the reasons for premature systemic aging are a mystery and difficult to study in humans. Here we show that chromosome amplification in wild yeast also produces premature aging and shortens life span. Chromosome duplication disrupts nutrient-induced cell-cycle arrest, entry into quiescence, and cellular health during chronological aging, across genetic background and independent of which chromosome is amplified. Using a genomic screen, we discovered that these defects are due in part to aneuploidy-induced dysfunction in Ribosome Quality Control (RQC). We show that aneuploids entering quiescence display aberrant ribosome profiles, accumulate RQC intermediates, and harbor an increased load of protein aggregates compared to euploid cells. Although they maintain proteasome activity, aneuploids also show signs of ubiquitin dysregulation and sequestration into foci. Remarkably, inducing ribosome stalling in euploids produces similar aging phenotypes, while up-regulating limiting RQC subunits or poly-ubiquitin alleviates many of the aneuploid defects. We propose that the increased translational load caused by having too many mRNAs accelerates a decline in translational fidelity, contributing to premature aging.

Aneuploidy↗

DOE OSTI2024

Associations between regional blood-brain barrier permeability, aging, and Alzheimer’s disease biomarkers in cognitively normal older adults

Background Increased blood-brain barrier permeability (BBBp) has been hypothesized as a feature of aging that may lead to the development of Alzheimer’s disease (AD). We sought to identify the brain regions most vulnerable to greater BBBp during aging and examine their regional relationship with neuroimaging biomarkers of AD. Methods We studied 31 cognitively normal older adults (OA) and 10 young adults (YA) from the Berkeley Aging Cohort Study (BACS). Both OA and YA received dynamic contrast-enhanced MRI (DCE-MRI) to quantify K trans values, as a measure of BBBp, in 37 brain regions across the cortex. The OA also received Pittsburgh compound B (PiB)-PET to create distribution volume ratios (DVR) images and flortaucipir (FTP)- PET to create partial volume corrected standardized uptake volume ratios (SUVR) images. Repeated measures ANOVA assessed the brain regions where OA showed greater BBBp than YA. In OA, K trans values were compared based on sex, Aβ positivity status, and APOE4carrier status within a composite region across the areas susceptible to aging. We used linear models and sparse canonical correlation analysis (SCCA) to examine the relationship between K trans and AD biomarkers. Results OA showed greater BBBp than YA predominately in the temporal lobe, with some involvement of parietal, occipital and frontal lobes. Within an averaged ROI of affected regions, there was no difference in K trans values based on sex or Aβ positivity, but OA who were APOE4carriers had significantly higher K trans values. There was no direct relationship between averaged K trans and global Aβ pathology, but there was a trend for an Ab status by tau interaction on K trans in this region. SCCA showed increased K trans was associated with increased PiB DVR, mainly in temporal and parietal brain regions. There was not a significant relationship between K trans and FTP SUVR. Discussion Our findings indicate that the BBB shows regional vulnerability during normal aging that overlaps considerably with the pattern of AD pathology. Greater BBBp in brain regions affected in aging is related to APOE genotype and may also be related to the pathological accumulation of Aβ.

Science & Technology - Other Topics↗

DOE OSTI2026

[C/N] Ages for Red Giants and Their Implications for Galactic Archaeology

Red giants undergo the first dredge-up, a mixing event that creates a connection between their surface [C/N] and their mass and age. We derive a [C/N]–age relationship for red giants calibrated on Apache Point Observatory Galactic Evolution Experiment (APOGEE) DR17 abundances and APOKASC-3 asteroseismic ages. We find that we can use [C/N] to reliably recover asteroseismic ages between 1 and 10 Gyr with average uncertainties of 1.64 Gyr. We find that [C/N] yields concordant ages, with modest offsets, for stars in different evolutionary states. We also find that the [C/N]–birth mass relationship is robust for luminous giants, and argue that this is an advantage over direct asteroseismology for these stars. We use our ages to infer Galactic birth abundance trends in [Fe/H] and [Mg/H] as a function of position in the Galactic disk. We filter out stars with kinematic or chemical properties consistent with migrators and find the number of migrators to be much lower than expected by standard radial migration prescriptions. The remaining population shows weak chemical evolution trends, on the order of 0.01 dex Gyr −1 , over the last 10 Gyr across a wide range of radii.

Roberts, John D. [The Ohio State Univ., Columbus, ↗

NASA NTRS1973

Pb-207/Pb-206 ages of individual mineral phases in Luna 20 material by ion microprobe mass analysis.

Ion microprobe analyses of returned lunar material have helped to demonstrate that U, Th, and radiogenic Pb are concentrated in small accessory mineral phases. It is possible to measure the isotopic composition of this Pb and obtain a radiometric Pb-207/Pb-206 age for the mineral. The ages so derived compare favorably with crystallization ages determined by conventional methods. A grain mount (22003,2/6) of Luna 20 material was searched for such accessory mineral phases, and two were found. One of these phases give an age of 4.12 plus or minus 0.04 b.y. and the other an age of 4.42 plus or minus 0.11 b.y. Ages of minerals dated by the ion probe in Apollo samples 14310 and 15555 are given for comparison. Data on the upper limit for Pb concentration in the outermost surface layers of free lunar soil particles are also given.

Andersen, C. A.↗

NASA NTRS1975

Effects of long-term aging on ductility of the columbium alloys C-103, Cb-1Zr, and Cb-752 and the molybdenum alloy Mo-TZM

A program was conducted to determine if aging embrittlement occurs in the columbium alloys C-103, CB-1Zr, and Cb-752 or in the molybdenum alloy Mo-TZM. Results showed that aging embrittlement does not occur in C-103, Cb-1Zr, or Mo-TZM during long-term (1000 hr) aging at temperatures in the range 700 to 1025 C. In contrast, aging embrittlement did occur in the Cb-752 alloy after similar aging at 900 C. A critical combination of the solute additions W and Zr in Cb-752 led to Zr segregation at grain boundaries during long-term aging. This segregation subsequently resulted in embrittlement as indicated by an increase in the ductile-brittle transition temperature from below -1960 C to about -150 C.

Stephens, J. R.↗

NASA NTRS1977

Effects of long-term aging on ductility and microstructure of Cb and Mo alloys

A program was conducted to determine if aging embrittlement occurs in columbium-base alloys C-103, Cb-1Zr, and Cb-752 or in a molybdenum alloy, Mo-TZM. Results showed that aging embrittlement does not occur in C-103, Cb-1Zr, or Mo-TZM during long-term (1000 hour) aging at temperatures in the range of 700-1025 C. In comparison, aging embrittlement occurred in the Cb-752 alloy after similar aging at 900 C. A critical combination of the solute additions W and Zr led to Zr segregation at grain boundaries during long-term aging which subsequently resulted in embrittlement as indicated by an increase in the ductile-brittle transition temperature from below -196 C to about -150 C.

Stephens, J. R.↗

NASA NTRS1976

Ages of flow units in the lunar nearside maria based on Lunar Orbiter IV photographs

A map dividing the lunar nearside maria into six units each of uniform age was compiled from Lunar Orbiter IV photographs. Relative ages were determined using a crater morphology technique. Relative ages were then converted to absolute ages by comparison to a curve calibrated from Apollo and Luna sample data; three of the six units, including the two youngest (about 3.1 and 2.6 b.y. old), were not sampled by Apollo or Luna. Vast regions in the western maria are covered by these young flows. The old flows (about 3.75 b.y. in age) are found to occur mostly in the eastern maria. A comparison of the age units derived from these data with those units derived from other remote-sensing data provide good agreement in the location of unit boundaries. These data also indicate that the emplacement history of mare basalt types is more complex than was earlier thought.

Boyce, J. M.↗

NASA NTRS1977

/Ar-39/-/Ar-40/ ages of lunar rocks

The (Ar-39)-(Ar-40) ages for 21 lunar samples from Apollo 14, 15, 16, and 17 are presented. The cosmic-ray exposure ages, Ca, and K contents are also measured. Mare basalt 15075, a slowly cooled pyroxene-phyric basalt, has a (Ar-39)-(Ar-40) plateau age of 3.45 + or - 0.2 billion years. This is one of the oldest mare basalts found at Apollo 15. 65777, a recrystallized noritic breccia, has a plateau age of 3.72 + or - 0.02 billion years, relatively young for a highland rock. This rock is probably related to a cratering event over 200 m.y. post Imbrium. Similarly breccia 68516 was formed 150 m.y. post Imbrium. Histograms for the (Ar-39)-(Ar-40) plateau ages strongly suggest that the peak in ages at Apollo 14, 16, and 17 of about 4 billion years is caused by the dominance of Imbrium ejecta at these landing sites.

Schaeffer, G. A.↗

NASA NTRS1980

Age related changes in the bone tissue under conditions of hypokinesia

Microroentgenography of nine young people, aged 24-29, before and after hypokinesia (16-37 days strict bed rest), showed that the heel bone density of those with initially high bone density generally decreased and that of those with initially low bone density generally increased. X-ray structural analysis of the femurs of 25 corpses of accidentally killed healthy people, aged 18-70, data are presented and discussed, with the conclusion that the bone hydroxyapatite crystal structure stabilizes by ages 20 to 25, is stable from ages 25 to 60 and decreases in density after age 60. It is concluded that bone tissue structure changes, both with age, and in a comparatively short time in hypokinesia.

Podrushnyak, E. P.↗

NASA NTRS1981

Ar-40-Ar-39 and Rb-Sr age determinations on Quaternary volcanic rocks

Ages of leucite and biotite separates from samples of the potassic volcanics of the Roman Comagmatic region are derived by the stepwise degassing variant of the Ar-39-Ar-40 dating method and compared with those derived from Rb-Sr dating in order to evaluate the abilities of the methods to date Quaternary geological events. Six of the leucite separates are found to contain Ar with very high bulk 40/36 ratios and to have well correlated Ar-40 and Ar-39 contents, yielding ages of approximately 338,000 years. Two leucites observed to contain Ar with lower bulk 40/36 ratios and Ar-40/Ar-36 ratios significantly lower than atmospheric are found to have ages in substantial agreement with those of the other leucites despite the uncertainty in the composition of the trapped component. Ages obtained for the biotites are not as precise as those of the leucites, due to difficulties in obtaining a good separation of in situ radiogenic Ar-40 from trapped Ar-40. Ages determined from Rb-Sr measurements for selected tuff samples are found to be in good agreement with the Ar-40-Ar-39 ages of the leucites. Results demonstrate the possibility of attaining precisions of better than 5% in the dating of rocks 350,000 years old by both the Ar-40-Ar-39 and the Rb-Sr methods.

Radicati Di Brozolo, F.↗

NASA NTRS1982

Nuclear constraints on the age of the universe

A review is made of how one can use nuclear physics to put rather stringent limits on the age of the universe and thus the cosmic distance scale. The age can be estimated to a fair degree of accuracy. No single measurement of the time since the Big Bang gives a specific, unambiguous age. There are several methods that together fix the age with surprising precision. In particular, there are three totally independent techniques for estimating an age and a fourth technique which involves finding consistency of the other three in the framework of the standard Big Bang cosmological model. The three independent methods are: cosmological dynamics, the age of the oldest stars, and radioactive dating. This paper concentrates on the third of the three methods, and the consistency technique.

Schramm, D. N.↗

NASA NTRS1983

The primordial helium abundance and the age of the universe

The value of the primordial helium abundance as a constraint on the age of the universe is discussed emphasizing the age of the oldest stars as an estimate of the age of the universe. The primary uncertainty in the globular cluster technique is that of the starting helium abundance. Investigations of this abundance are reviewed, and the consistency of the resulting findings with the age determinations obtained by cosmological dynamics and big bang nucleosynthesis studies is discussed. It is concluded that the age of the universe is probably between 8 and 19 billion years, and that the best fit age consistency determined by a combination of all techniques is about 15 billion years.

Schramm, D. N.↗

NASA NTRS1983

Nuclear constraints on the age of the universe

Schramm, D. N.↗

NASA NTRS1984

A sample of solar-type stars of known age

A sample of field F and G dwarfs of known ages is presented. All the dwarfs are secondaries of visual binaries in which the temperature and gravity of the hotter primary has been estimated from Stromgren photometry, and its age derived from reference to isochrones. This age is taken to apply to the secondary. Even in the case of F-type secondaries, which themselves have measured Stromgren indices, it is much better to estimate ages from the primaries as it is demonstrated that use of isochrones to determine age of stars not far evolved from the main sequence can lead to significant systematic overestimates of ages when the photometric measurements have typical random errors. A number of systems in which photometry is available for both components have primaries which appear much younger than the secondaries, suggesting a need for further investigation.

Duncan, D. K.↗

NASA NTRS1984

Muscularity as a function of species, sex and age in small mammals

Changes in the body skeletal muscle mass SMM (measured as a function of the ratio between the body creatine mass and the fat-free muscle creatine), and in muscularity (expressed as the ratio of SMM to fat-free body mass) were studied as functions of age, sex, and species in mouse, rat, hamster, guinea pig, and rabbit. Six animals of each sex were examined in eight age cohorts ranging from 1 to 24 months. Both species and age factors affect SMM. Strong sexual dimorphism in the SMM changes with age was displayed by mouse, rat, and guinea pig, whereas the hamster and rabbit were statistically monomorphic. The mouse, rat, and hamster attain a maximal SMM at about 1 year of age, whereas in the guinea pig and rabbit the decrease in SMM starts after 2 years. The value of muscularity reached a peak at age of 2-3 months in all animals of both sexes, with a pronounced difference among the species. The mouse emerged as the most muscular, while the guinea pig the least muscular, of all species.

Pace, N.↗

NASA NTRS1989

Rotational dating of middle-aged stars

By the age of about 100 million years, the rotational velocity of solar mass stars becomes independent of the initial rotation rate on the main sequence, due to the strong dependence of the angular momentum loss rate on the rotation rate; once this common value is reached, the rotation velocity depends only on time and the mass of the star. Thus, the measured rotation rate of a low-mass star provides an estimate of its age when its mass is known. The observed rotation periods of low-mass stars in the Hyades are used to test this conclusion and to check the validity of the theoretical angular momentum loss rates. Adapting the magnetic braking model of Kawaler (1988), the angular momentum loss rate is integrated to derive a relation between rotation period and age, and this relation is converted to a period-age-color relation using simple stellar models. Using this method, a mean rotational age for the Hyades is obtained which is in close agreement with the age determined by isochrone fitting.

Kawaler, Steven D.↗

NASA NTRS1990

Calibration of the C-14 timescale over the past 30,000 years using mass spectrometric U-Th ages from Barbados corals

Uranium-thorium ages obtained by mass spectrometry from corals raised off the island of Barbados confirm the high precision of this technique over at least the past 30,000 years. Comparison of the U-Th ages with C-14 ages obtained on the Holocene samples shows that the U-Th ages are accurate, because they accord with the dendrochronological calibration. Before 9,000 yr BP, the C-14 ages are systematically younger than the U-Th ages, with a maximum difference of about 3500 yr at about 20,000 yr BP. The U-Th technique thus provides a way of calibrating the radiocarbon timescale beyond the range of dendrochronological calibration.

Bard, Edouard↗

NASA NTRS1991

Space aging of solid rocket materials

Solid rocket propellant and rocket motor components were aged in a vented container on the interior of the LDEF. The results of aging IPSM-II/PAM-DII space motor components are presented. Ballistic and mechanical properties of the space aged main propellant, igniter propellant, and ignition system were compared with similar data from preflight and ground aged samples. Mechanical properties of the composite materials and bonded joints used in the motor case, insulation, liner, nozzle, exit cone, and skirt were similarly evaluated. The space aging results are compared to data collected in a ground based vacuum aging program on similar components.

Lester, Dean M.↗