Breaking News
September 21, 2018 - Study reveals promising new drug candidate to treat acute renal failure
September 21, 2018 - Neural signal that urges to eat overpowers the one that says to stop
September 21, 2018 - Scientists achieve breakthrough in accelerated diagnosis of multi-resistant hospital pathogens
September 21, 2018 - Researchers simulate how different breast tissues respond to heat from MRIs
September 21, 2018 - Despite red flags at surgery centers, overseers award gold seals
September 21, 2018 - Zapping Airway Nerves May Help COPD Patients Breathe
September 21, 2018 - Researchers find answers as to why some people are at risk of gout
September 21, 2018 - Stars of Stanford Medicine: Genetic counseling and compassion
September 21, 2018 - Health insurance ads have shifted over time due to health plans offered via ACA
September 21, 2018 - Use of transcranial electrical stimulation to bolster creativity has far-reaching implications
September 21, 2018 - Scientists find way to boost efficacy of powerful antimalarial drug with anti-cancer medicines
September 21, 2018 - Weighing the risks and benefits of drug tapering—two patients, two perspectives
September 21, 2018 - The “exposome” revealed: a barrage of bacteria, chemicals, microscopic animals and more
September 21, 2018 - Top three immune boosting recommendations to ward off freshers’ flu
September 21, 2018 - Young children’s oral microbiota could serve as early indicator for obesity
September 21, 2018 - Older individuals with multiple sclerosis report higher quality of life than younger counterparts
September 21, 2018 - LineaRx signs agreement with Takis/Evvivax to develop linear-DNA based anti-cancer vaccines
September 21, 2018 - AbbVie Presents Upadacitinib Longer-Term (32-Week) and Patient-Reported Outcomes Data from Phase 2b Atopic Dermatitis Study at 27th European Academy of Dermatology and Venereology (EADV) Congress
September 21, 2018 - Alzheimer’s drug may stop disease if used before symptoms develop
September 21, 2018 - Human skeletal stem cell can generate cartilage, bone
September 21, 2018 - UK and European research collaborations receive vote of confidence by three major cancer charities
September 21, 2018 - Microbiota in the intestines and cell stress cause colon cancer
September 20, 2018 - Arizona EMTs have 39% higher risk for suicide than general public
September 20, 2018 - Driving and older adults: MedlinePlus Medical Encyclopedia
September 20, 2018 - Brain region for stress control is enlarged in people with depression, finds study
September 20, 2018 - Researchers test autobiographical memory for early Alzheimer’s detection
September 20, 2018 - Organizations join forces to help teens with severe mental health challenges | News Center
September 20, 2018 - Neurons in the human brain can encode numerical information
September 20, 2018 - Potential drugs to treat neurodegenerative diseases garner $3 million grant
September 20, 2018 - Processing speed important to higher order cognitive function in multiple sclerosis patients
September 20, 2018 - Helping a patient survive a hurricane
September 20, 2018 - Tafamidis Treats Transthyretin Amyloid Cardiomyopathy
September 20, 2018 - Low academic achievement can lead to drug abuse decades later, research finds
September 20, 2018 - Study identifies stem cell that gives rise to new bone, cartilage in humans | News Center
September 20, 2018 - Celltrion and Emory University sign ‘Incubation’ agreement to develop new drug candidates for atherosclerosis
September 20, 2018 - TGen and PNOC take part in launch of NIH-supported Kids First Data Resource Portal
September 20, 2018 - Could Household Cleaners Make Your Kid Fat?
September 20, 2018 - Addiction nonprofit makes searching for services simple
September 20, 2018 - We are bombarded by thousands of diverse species and chemicals | News Center
September 20, 2018 - Experts to Present Prostate Cancer Advances at Patient Summit
September 20, 2018 - Alector announces initiation of Phase 1 trial of AL001 for treating frontotemporal dementia
September 20, 2018 - Pfizer’s 20vPnC vaccine receives Breakthrough Therapy designation from FDA
September 20, 2018 - Study could allow doctors to screen patients at risk from Aspergillus
September 20, 2018 - Emergex signs MoU with Brazil’s Fiocruz for development of viral vaccines
September 20, 2018 - The ‘real you’ is a myth – we constantly create false memories to achieve the identity we want
September 20, 2018 - Researchers describe cell mechanism that optimizes proteins production in stressful situations
September 20, 2018 - Cell Medica successfully doses first patient with CMD-501 targeting pediatric neuroblastoma
September 20, 2018 - Sesen Bio to present its three-month Phase 3 VISTA Trial data at Global Congress
September 20, 2018 - Senators unveil legislation to protect patients against surprise medical bills
September 20, 2018 - Study provides insights into development of special-purpose cosmetic products
September 20, 2018 - Research shows enlarged genotype-phenotype correlation for three-base pair deletion in NF1
September 20, 2018 - 91% of people around the world believe medical research will result in dementia cure
September 20, 2018 - DePuy Synthes introduces CONCORDE LIFT Expandable Interbody Device at EUROSPINE 2018
September 20, 2018 - Manx Telecom unveils MT clearSound that improves clarity of mobile phone calls
September 20, 2018 - Mediterranean-style diet appears to reduce stroke risk in women
September 20, 2018 - AbbVie Announces Patient-Reported Outcomes Data from Three Pivotal Phase 3 Studies of Risankizumab, Showing Significant Improvements in Health-Related Quality of Life for Patients with Psoriasis
September 20, 2018 - Characterization of pregnancy microbiome reveals variations in bacterial diversity
September 20, 2018 - New guidance for treatment of bone loss in hematologic stem cell transplant Recipients
September 20, 2018 - Experts to present research on prevention, management of dysphagia at international conference
September 20, 2018 - New study focuses on two-way gene switches controlling gene activity
September 20, 2018 - Zika virus could become a weapon against brain cancer
September 20, 2018 - Home-based video game exercises can reduce chronic low back pain in older people, study finds
September 20, 2018 - Investigators find that bile acids reduce cocaine reward
September 20, 2018 - Cannabinoid drugs reduce perceived unpleasantness of painful stimuli and increase tolerance
September 20, 2018 - Health care companies’ data could enable more accurate flu season forecasts
September 20, 2018 - Geroscience takes center stage in Journal of the American Medical Association
September 20, 2018 - Ambient Particulate Matter Linked to Emergency Asthma Care
September 20, 2018 - Patient satisfaction with plastic surgery—it’s the surgeon, not the practice
September 20, 2018 - Medicine is a team sport – and that’s exactly how it should be
September 20, 2018 - Logos Biosystems releases new electrophoretic tissue clearing system with twice the features in half the space
September 20, 2018 - Novel micro-platform reveals never-before-seen behaviors of cancer cells
September 20, 2018 - PAREXEL partners with Datavant to enhance clinical study design and generate real-world evidence
September 20, 2018 - Robert Koch Institute publishes new data on allergies, mental health problems, and accident injuries
September 20, 2018 - Study finds higher readmission rates in for-profit hospitals
September 20, 2018 - Encouraging youth to do strength-based exercises could help tackle child obesity
September 20, 2018 - Sleep apnea, congenital heart disease in hospitalized infants strongly associated with death
September 20, 2018 - Researchers find way to map mysterious content of non-coding RNA
September 20, 2018 - Air Pollutants Reach Placenta, Might Harm Fetus: Study
September 20, 2018 - Sleep apnea, congenital heart disease may be deadly mix for hospitalized infants
September 20, 2018 - My relative has cancer, should I worry? Encouraging cascade genetic testing
Father’s age can affect offspring lifespan, mice study shows

Father’s age can affect offspring lifespan, mice study shows

image_pdfDownload PDFimage_print

How does the father’s age at conception affect his children? Researchers at the German Center for Neurodegenerative Disease (DZNE) and fellow scientists have studied this question in mice. Their findings, which have been published in the Proceedings of the National Academy of Sciences (PNAS), show that the offspring of elderly mouse-fathers had a shorter lifespan than those of young fathers and featured an exacerbation of a number of histopathological and molecular aging traits. Moreover, sperm of old males as well as the tissue from old father offspring featured shared epigenetic changes and altered activation states of longevity-related signaling pathways. These results are indicative of intergenerational influences on aging processes and they could potentially be of relevance for a human context.

In Western societies, the average age of parenthood has become increasingly older. This is not without complications, as a mother’s old age, for instance, has long been identified as a risk factor for child health. Moreover, it has turned out that an advanced age of the father at the time of conception can also have unfavorable consequences for offspring.

“Statistically, certain diseases occur more often in children of old fathers than in the offspring of young men. This is the case, for example, for psychiatric disorders such as autism or schizophrenia,” explains Dr. Dan Ehninger, head of a research group at the DZNE’s Bonn site. His team led the current study, which also involved scientists from the German Mouse Clinic in Munich and other institutions. “Associations between paternal age and health outcomes in offspring, described by a number of epidemiological studies, could arise for many reasons. We wanted to address whether age-related biological changes in the male germ line could underlie effects on offspring health. Our study was focused specifically on lifespan and aging-associated pathologies in old father offspring.”

Mouse studies

The scientists assessed two groups of mice that included the descendants of young and old fathers, respectively. Young mouse-fathers were mated at an age of four months – an age that mice are considered as young adults – while the old fathers with an age of at least 21 months were already seniors. The mouse-mothers were all four months old. All fathers belonged to a genetically defined mouse strain. This also applied to the dams. All offspring grew up under the same living conditions and never had contact with their fathers. Rodents from both groups were examined at the age of six and 19 months, respectively.

“We looked at 13 biological parameters that had previously been shown to change during natural aging in mice. These included deposits in the kidneys, tissue changes in the lungs, as well as alterations in proteins associated with oxidative stress,” says Prof. Martin Hrabe de Angelis, director of the German Mouse Clinic in Munich. Studies with descendants of old mouse-fathers have been performed previously, Hrabe de Angelis points out. “However, data are scarce with regards to paternal age effects on aging-associated changes in progeny.”

Shorter lifespan

The studies revealed that age-associated traits were more pronounced in the 19-month-old offspring of elderly mice than in age-matched descendants of young fathers. “If you take our parameters as a reference, then you can certainly say that the descendants of the old mouse-fathers aged faster than the offspring of young fathers,” says Dr. Kan Xie, a researcher in Ehninger’s team and one of the first authors of the current publication. Paternal age effects were also evident with regards to lifespan: Offspring of young fathers showed a median lifespan about two months longer than that of peers with old fathers.

Control elements of the DNA

The scientists do not assume that the different development was caused by defects in the offspring’s genome. “Comparing the two groups of mice, we found no significant differences in mutation rates, at least not with the methodology employed in the present study,” says Ehninger. However, the researchers discovered alterations in the sperm of the fathers with regards to epigenetic marks of the genome carried by sperm. This concerned methyl groups attached to the DNA. These chemical modifications help to switch regions of the genome on and off, thus regulating gene activity.

“With regards to the methylation patterns of sperm, we observed notable differences between young and old mouse fathers. In fact, this may not be surprising, given that it has been known for some time that methylation can change with age and living conditions,” explains Ehninger. Interestingly, the scientists discovered similar DNA methylation differences in offspring. “We noted an overlap between fathers and offspring, suggesting that these marks may have been passed on to the next generation.” Ehninger explains that formerly it was assumed that paternal epigenetic marks are erased completely upon fusion of sperm and egg cell. “However, it is known nowadays that the process of clearing methylation marks from the paternal genome is incomplete.”

In the current study, this affected genes with a role in the regulation of lifespan and aging-associated pathologies. “We could show that the offspring of old fathers showed an increased activation state of the mTORC1 signaling pathway. This pathway is known to be an important regulator of growth and many metabolic processes,” says Ehninger.

What about humans?

What are the implications of these results for a human context? “What we have described here are fundamental mechanisms in a mammalian model organism. These could also be relevant for humans. However, whether this is the case and, if so, to what extent has not been tested by our study and remains unknown. In this respect, our results cannot be directly applied to humans,” says Ehninger. As he points out, data on the extent to which epigenetic marks of human sperm change with age are limited so far. “However, our results provide a good reason to take a closer look at this.”​​

Tagged with:

About author

Related Articles