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stem cell aging

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Antonio Diez-Juan

on 6 November 2018

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Transcript of stem cell aging

Aging Causes Collateral Rarefaction & Disfunction
Envejecimiento y metabolismo
En envejecimiento hay una rarefacción y disfunción microvascular
Rarefación microvascular y disfunción afecta al estado energético del tejido/célula
Alteraciones en el estado energético del tejido/célula afectan a la microvasculatura
Aging not universal.
'Healthy aging' is an oxymoron like a healthy dying or a healthy diseaseMore accurate terms instead of 'healthy aging' would be a delayed aging, postponed aging, slow aging, or negligible aging (senescence)
Vascular Rarefaction and disfunction: Efects beyond metabolic support
Stem cell niches
Tissue turnover
Muchas Gracias
Why We age??

Evolutionary
Mutation accumulation:
Mutations that affect health at older ages are not selected against.
Disposable soma*:
Somatic cells are maintained only to ensure continued reproductive success; after reproduction, soma becomes disposable.
Antagonistic pleiotropy
* : Genes beneficial at younger age become deleterious at older ages.
Molecular
Gene regulation*
: Aging is caused by changes in the expression of genes regulating both development and aging.
Codon restriction:
Fidelity/accuracy of mRNA translation is impaired due to inability to decode codons in mRNA.
Error catastrophe
: Decline in fidelity of gene expression with aging results in increased fraction of abnormal proteins.
Somatic mutation :
Molecular damage accumulates, primarily to DNA/genetic material.
Dysdifferentiation :
Gradual accumulation of random molecular damage impairs regulation of gene expression.
Cellular
Cellular senescence:
Telomere theory* Phenotypes of aging are caused by an increase in frequency of senescent cells. Senescence may result from telomere loss (replicative senescence) or cell stress (cellular senescence).
Free radical*
Oxidative metabolism produces highly reactive free radicals that subsequently damage lipids, protein and DNA.
Wear-and-tear
Accumulation of normal injury.
Apoptosis
Programmed cell death from genetic events or genome crisis.
System
Neuroendocrine*
Alterations in neuroendocrine control of homeostasis results in aging-related physiological changes.
Immunologic*
Decline of immune function with aging results in decreased incidence of infectious diseases but increased incidence of autoimmunity.
Rate-of-living
Assumes a fixed amount of metabolic potential for every living organism (live fast, die young).
(Austad & Fischer, 1991)
Longevity and body mass in
nonflying eutherian mammals
Bats are long-lived because they save energy by going into torpor or hibernate (Bouliere 1958)
But, nonhibernating tropical bat species live as long as temperate species (Herreid 1964)
Furthermore, bats live longer than expected for their body size even after adjusting for metabolic differences (Jurgens and Prothero 1987)
And, marsupials, which have lower metabolic rates than bats, have much shorter life spans (Austad and Fischer 1991)
Flying mammals live longer than nonflying mammals (Holmes and Austad 1994)
Aging studies and bats
Twente et al. 1985
Hibernation
Bat diets
Carollia perspicillata
Nyctophilus gouldi
Rhinolophus darlingi
2 pups/yr
1 pup/4-6 mos
1 pup/yr
Reproductive effort variation
Allometric relationship for 463 spp of nonflying placental mammals (Austad & Fischer 1991)
F 1,40 = 7.3, P = 0.01
F 1,62 = 1.5, P = 0.23
Independent contrasts
Species means
Longevity (y)
Change in longevity (log y)
Change in body mass (log g)
Body mass (g)
Longevity and body mass in bats
Pteropus
Giganteus
(31 yrs, 1 kg)
Myotis brandti (38 yrs, 8 g)
Myotis lucifugus (34 yrs, 7 g)
Myotis blythii (33 yrs, 23 g)
Plecotus auritus (30 yrs, 7 g)
Rhinolophus ferrumequinum (31 yrs, 24 g)
Bat Methuselahs
F 1,5 = 10.3, P = 0.024
F 1,60 = 13.7, P = 0.0005
Longevity (y)
Change in longevity (log y)
Change in hibernation
Hibernation
Hibernation and longevity
Mutation
“Population speciation through Natural Selection”
Individuals with this mutation happen to leave more offspring
(greater “fitness”)
This mutation happens to be beneficial
Rejuvenation. “run the tape backwards”?
Cloned Mammals, Whose Nuclei Came From Adult Somatic Cells
Rejuvenation. “run the tape backwards”?
iPS suggest an alternative source of stem cells
From Nishikawa et al, 2008
Copyright © American Heart Association
Faber J E et al. Arterioscler Thromb Vasc Biol 2011;31:1748-1756
Aging causes a greater drop in perfusion immediately after FAL, poorer recovery of perfusion, and fewer α-smooth muscle actin–positive vessels in adductor collateral zone. a, Laser Doppler perfusion imaging of plantar foot (correlates with leg flow). b, Pla...
Copyright © American Heart Association
Faber J E et al. Arterioscler Thromb Vasc Biol 2011;31:1748-1756
Aging causes collateral circulatory insufficiency in hindlimb. a to c, Greater hindlimb ischemia, use impairment, tendency for decline in native collateral diameter (before FAL), and reduced collateral remodeling after FAL. d, Aging impairs ischemic angioge...
Copyright © American Heart Association
Faber J E et al. Arterioscler Thromb Vasc Biol 2011;31:1748-1756
Aging causes rarefaction of native cerebral collateral diameter and number. a, Image of dilated, fixed, and filled pial cortical circulation. b, Higher magnification image shows 2 collaterals (dotted lines) and penetrating arterioles (asterisks) branching f...
Aging and the Stem cell niche
Why we age?
Vascular aging
Agi
Aging
.
Endothelial cell disfunction
Stem cell malfunction
BK:Bradiquinina

Aging not universal.
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