seX & whY من Dr. Jeannette Wolfe

Show Notes for Episode Twenty-Six of seX & whY: Sex and Gender Differences in Aging

Host: Jeannette Wolfe Guest: Sara Haag

Dr Haag is a researcher in molecular epidemiology who studies human biological aging at the Karolinska Institute in Stockholm.

Background - Dr Haag has a PhD in functional genomics and Post Doc in genetic and molecular epidemiology. She studies telomeres and molecular association with telomere length, she also has experience in molecular biology and computer science.

Definitions and discussion points from podcast

• Geroscience - a new field of biomedical science that looks at how the molecular, genetic, and cellular mechanisms associated with the aging process itself may interact and even trigger many diseases associated with aging. This research provides a different angle for potential intervention to enhance health and longevity. 
• Life Span - time between birth and death.
• Heath Span - time within life span of good health.
• Frailty Index and Clinical Frailty Scale are tools that evaluate a patient’s overall physical conditioning and their vulnerability to certain adverse outcomes including falls, increased care requirements, hospital admission,  and mortality. 
• Epigenetics - the study of how DNA expression can be modified by behavior or environmental factors (versus alteration in the actual DNA itself). One way I think of this is to imagine a huge library full of books, and that each book represents a gene coded from our DNA- epigenetics help determine which books get pulled off the shelfs and get read or pushed back deeper into the shelfs.  This process is different than buying new books for the library (which would be equivalent to changing the DNA itself.) 
• Aging Scales - as different elements of the body age differently, there is not a gold standard to measure aging. Dr Haag recently published a study that evaluated a bunch of these different scales and determined that the “ideal” scale will vary dependent upon what you are studying- such as overall function or the biological aging of a specific organ (i.e. heart or liver).  

Two major theories of aging:

• Senescence theory of aging - the belief that with age, cellular systems due to repeat exposure to intracellular and extracellular stressors, eventually start to malfunction and breakdown.  Things start slowly falling apart due to wear and tear. 
• Programmed theory of aging - Aging is an innate active process which is highly regulated by an internal time clock. 

As the field of Geroscience and epigenetics evolves, the “truth” around aging is likely to be a combo of both theories. 

Sex Differences

Hormones

Estrogen

Dr Haag talked about research involving telomere length (telomeres are the cap of the chromosome and they help protect the chromosomes from damage.) Typically, telomeres shorten with repeated division in somatic cells and when they shrink to a certain length the cell is more vulnerable to error and damage. Females have longer telomere length at birth compared to males and there is evidence that women with longer exposure to estrogen have longer telomeres.                   

Testosterone

Here is the Korean Eunuch study mentioned in the podcast.  The researchers examined a genealogical record of 385 eunuchs and compared their life span to several other groups of men who lived during the same time periods including a bunch of kings. They found that the average life span of a eunuch was 70 which was 15-19 years longer than the comparison groups. One theory behind this difference in longevity is “the disposable soma theory”. This postulates that in males there is competition between two different intrinsic systems - somatic aging and reproduction- and that as both systems require significant energy to maintain,  when energy is diverted to one system the other suffers.  

Sex Chromosomes

In females each cell has two X chromosomes. In female cells, one of the X chromosomes is typically inactivated so that some cells have genes expressed that are inherited by their father, while others express genes inherited from their mother. Complicating this further is that several genes do not fully inactivate that second X chromosomes so that females may have an “extra” expression of some genes. A concrete example of this is the gene Toll like receptor 7 which codes for proteins that helps the immune system recognize the early invasion of certain types of viruses. As this gene doesn’t undergo X inactivation, it may give females an extra boost in warding off certain types of viral infections. 

With aging there can be “skewing” of the X chromosome in that females may have a disproportionate percentage of cells that express the X chromosomes of a single parent.  

As male cells age, some may actually lose their Y chromosome. This news release suggests that his may happen relatively frequently as their work implied that 40% of all 70-year-olds had cellular evidence of it.  The loss of Y chromosome can be associated with Alzheimer’s and heart disease in males.   

Take home points:

1)    The field of aging is absolutely exploding. Someday it may be possible to actively manipulate epigenetic signaling to slow or even reverse aging processes.  

2)    Different biological processes in our bodies age at different rates. Plus, if you follow a group of people over time, as they get older there will be greater and greater differences within that group in their markers of aging.

3)    In aging research, there has historically been two different camps- the senescence camp, and the programmed theory one. In the senescence camp is the belief that as we age, things just start breaking down due to natural wear and tear. This contrasts with the programmed theory camp which believes that aging is a pre-designed active process that is triggered with age. The “truth” likely is a combination of both theories with epigenetics being the bridge. 

4)    Sex differences in aging include the mortality-morbidity paradox in that although females tend to have poorer health and greater fragility risk, males still tend to die sooner. 

5)    Sex differences with aging may include changes in the X chromosome with increased skewing and even the loss of the expression of the Y chromosome, both of which can be associated with an increase of health-related issues.