2. Overview
* Problems of Womens’ Health in Ageing
* The science of the sex chromosomes: XIC and XIST
* Calico: Lyonization and the change in female mosaics in ageing
* Lifestyle influences on women health: X-skew
* Note
The science of Lyonization is well understood in the handling of the X-linked diseases
(Turner Syndrome, Fabry), but in ageing the health changes that are X-linked are
strongly epigenetics and unique for the individual. This presentation open the way to
social change to address this health issue.
3. EU Health crisis: ageing (65y) inequality of HLY
3 OECD Data 2014 at 65 years old
4. Healthy life years at age 65 as a share (Percent)
of remaining life expectancy, by sex, 2013
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MEN
Women
Sustainable Healthy Ageing
5. Healthy life years at age 65 as a share (Percent)
of remaining life expectancy, by sex, 2013
5
MEN
Women
Sustainable Healthy Ageing
6. Why Sexual Selection? X-chromosones?
* For a Species: the Males seem a waste of space and energy!
– Yet always 50% of the population is male, why are they useful? Fisher’s Principle
– Mammalian males are particularly wileful: Good father like wolves or bad father like dogs
* Males reduce the pathogenic risk to the whole population
* Y chromosome set the male form raise the pathogenic risk, female is the default form a safe form
for reproduction.
* X chromosomes triggers many epigenetics changes over the life span of the female
– Much speculation Sexual selection v Group or Kin selection
– Conjunctures : Grandmother hypothesis
• Female menopause: unique in humans, rhesus monkeys and whales: Grandmothers’ unique
role for the species
* Grandmother hypothesis is starting to fail in modern humans? No
– Human pathogenic risk is changing and X-skew not useful for population health
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7. Central Dogma of Genetics
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Future topic of
non-coding DNA
and health
APOE
> 90% coding
< 10% non-
coding
XIST
<5% coding
>95% non-coding
Barr body in cell
10. Mary F. Lyon: Mother of Lyonization X-inactivation
* 1961 at Harwell UK: Lyon discovered the random activation of X-
chromosomes
* One x- chromosomes needed to be suppression for a health female
– Two active x-chromosomes: Turner syndrome terminated eggs and ovaries
• XCI gene error and no XIST process (No Barr body in cell)
– Turner syndrome is rare condition in mature humans, not so rare in the female
fetus
* Birth of Lyonization: Epigenetics of female form for reproduction
– Female transform through different phases of body form for reproduction
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12. X-inactivation: Calico Cats to Calico
Humans
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UVA
Obvious in pigmentation
skin, retina, hair, eyes…
Also taste and other
sensor tissues
Teeth: front teeth are
from dexter grandma also
the index finger
13. Genetic Imprinting: Parent of Origin Effects
* X-inactivation is truly random for the first 30 cells
– remarkable itself
– Cells and daughters remain activated for ever
– Not just random effect on development: Lyonization has a purpose
* Genomics imprinting influences all alleles: 100% epigenetic
– Dominated by the sex-chromosomes
* Imprinting effects at each cell division, but vital importance to embryo
– Embryonic growth
– Development feeding
– Development motivation
– Immune system
* Genetic Imprinting amplifies the effects of X-inactivation over all alleles
– When X-skew in ageing happens in ageing it parent of origin effects that are
amplified.
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14. Women health in Ageing
* Women live longer than Men
* Women give most of the care in society: Grandmother hypothesis
* In an ageing society their health is critical to the robustness of the
population
* Women health in ageing is critical economically
–From Fisher’s Principle
• Males are not a waste of resource in general
• Males are the pathogenic Trojan Horse for the population
• Grandmothers are the
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15. Twin studies in Human Health
* Twin studies will used in human health and genetics studies
* Human twin monozygotic are not all clonal: all female humans are mosaics
* Problems of Lyonization are not always well presented in twin studies
– Affinity of MtDNA and maternal X not presented at all.
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18. Therapy
X-inactivation: Lifestyle Influence Control
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Environment impact
Skew in X-
X-skew
Mosaic
Infection, diet, sun, obesity, smoke, air, stress, drugs: Pathogens
Endocrinal multiplers: Phytoestrogens and BPA
Skew in X-
Optimal Pathogenic Risk for Population
Mosaic
19. X-skew changes with Age
* Environmental impact on the cells are identical: X-Skew is a selection effect
* Mitosis : X-skew and the imprinting or silencing of the X- chromosomes on all alleles
– X-skew effects: chromosomal disease of a mosaic
– Silencing and other epigenetic effects on all alleles: MtDNA
– Maternal MtDNA has high affinity to the maternal X less to the paternal X
• MtDNA starts to be extra cellular in ageing
* Lyonization is true for all female population: all health conditions can be studies and
studied now in ageing females
* Study of X-skew effects in ageing are better than Twin studies
– female twins are not clonal : due to X-inactivation
* Impact for consumer health: skin care
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