lecture 1 Flashcards
what is the definition of aging?
The time-dependent changes in a living organism
What is the definition of senescence?
the gradual deterioration of function that results in an increase in mortality of the organism
cellular senescence
cells no longer divide
definition of longevity?
the typical length of life for a species, this term is sometimes synonymous to life-expectancy
what is geroscience?
biology of aging and age related diseases
what did George Williams study?
Pleiotropy, natural selection, and the evolution of senescence
Antagonistic pleiotropy
- George Williams
-postulates that certain genes might have opposite effects on fitness at different ages
**something beneficial early in life is harmful at post-reproductive age
what is an example of antagonistic pleiotropy?
high testosterone levels
-benefit reproduction
-increase late life risk of prostate cancer
Mitochondrial DNA activity
-MtDNA is very important in early active stages of life
-but increases in activity in mitochondria when you are younger makes for issues later in life
Disposable Soma
energy is required for:
-metabolism
-reproduction
-repair and maintenance
Thomas Kirkwood believed that because metabolism and reproduction were the major focus of an organism(greater priority), so the repair and maintenance did not receive enough emphasis and so there is a gradual deterioration
supply of food is finite– the body must compromise
what is the explanation behind the disposable soma theory?
aging results from this accumulation of unrepaired cellular and molecular damage
longevity is controlled by the genes that regulates maintenance and repair
also, different types of damage contribute to aging= meaning that it is a complex network
what are the top leading causes of death in canada 2020?
malignant neoplasms (cancerous tumors) are number 1
diseases of the heart are 2nd
Risk for covid-19 infection, hospitalization and death by age group diagram
ages 18-29 were selected as the reference group because it accounted for the largest cumulative number of COVID-19 cases compared to other groups
-rate of death is 4x higher in ages 30-39, 330x higher in those who are 85+
-hospitalizations and deaths as age increased had a higher rate when compared to the reference age group
the cost of a long life
The United States spends the most per capita on health care - yet they do not have the highest average lifespan
-Japan has the highest average life spans
as of 2020, the average lifespan for Canada is 81.75 so approx. 82. For Japan it was 84.62, and for the US was 77.28.
-The US was seen as the outlier cause they spent so much, yet had a life expectancy of around 78 while Japan was around 82
labor income and consumption
people age out and do not work anymore and this affects the economy
-consumption continues to rise while labor income is shaped like a bell curve, at a certain age it declines
chronic diseases- US based
heart disease and stroke = kills the most people, cost the healthcare system the most
cancer= second leading cause of death
diabetes, obesity, arthritis, Alzheimer’s disease, epilepsy and cavities
cavities (tooth decay) is one of the most common diseases in the united states
Life expectancy in the United states
- has had a general increase which is very good
- in 1918 there was a plummet because of the Spanish Flu, H1 N1
in 2020, there was a minor decrease in life expectancy accounted for because of covid-19
life expectancy at birth, by sex 2000-2020
- trends seen are that women live longer than men, and this is seen in mammalian groups as well
-this graph also accounted for a minor dip in 2020 due to covid-19
lifespan (laboratory mouse)
- there are some genetic predispositions to lifespan differences
-not necessarily “anti aging genetics”
-predisposition to disease
-some strains of mice have different life spans, there is even diversity within a strain as well
e.g. Fisher rats are very prone to kidney disease so they are not used as much
there are also environmental factors, diet and other stressors that can affect the results - but most of these can somewhat be controlled in a lab
Squaring the curve
-extending average lifespan, but NOT extending maximum lifespan
-mechanisms of aging need to be identified and modified
longevity increases experiment
control group: 65% calories from carbohydrates
LCD ( low carbohydrate): 70% calories from fat
KD (Ketogenic diet): 89% calories from fat
-minor increases, low carb group lived slightly longer
Healthy aging
- hand grip strength males and females 50+
declines across both males and females as age increases
also in weightlifting: there are sex differences and age too - women have a much more significant decline
powerlifting: for sure age declines, but men and women are very similar so not much sex difference
For aging studies, what system or organism?
humans?
long-lived species?
species with unusual lifespans?
short-lived species like Drosophila, C. elegans
Rodents
-many strains, and transgenics available
cells
-yeast, cell culture
slow aging organisms
giant tortoise, tuatara, rockfish, cockatoo, bowhead whale
organisms age differently : rapid?
yeast, nematode, fruitfly, bamboo
organisms age differently: gradual?
mouse, humans
organisms age differently: negligible?
rockfish, tortoise, quahog clam, bristlecone pine
Negligible Senescence
- no observable age-related decline in physiological capacity or disease resistance
-no observable increase in age-specific mortality rate
-no observable decline in reproduction after sexual maturity
e.g. hydra, and Turritposis dohrnii (jellyfish)
in general the _______ the mammal the _______ the lifespan?
larger, longer
longevity quotient
-larger animals tend to live longer
LQ= actual lifespan/ predicted lifespan
-predicted based on body size
e.g. giraffe has an LQ of 1
-lifespan is 20-25 years
shrew and mice have very small LQ, humans have an LQ of 5.00 and the naked mole rate has 5.3 and the highest LQ is Brandt’s bat at 9.8
Longevity quotient for bats, non-bats
all non bats LQ was lower, bats LQ was rising up to 10 and naked mole rat was in between at about 5
Unusually aging species: Mole-rats and bats
naked mole rats
-live to their late 20’s
-10x lifespan of similar-sized mice
Bats
- many species known to live longer than 20 years
-Myotis brandti approx 41 years
considerations to make when making an aging study?
- it is a very gradual process
-what age do you study? do you examine very old animals?
-what tissues to study?
Rat muscle
vastus lateralis muscle
muscle weight and muscle fibre both go down as rat ages
comparison of 18 month and 36 month is very different
cardiac fibrosis
18 month versus 36 month
FBN rat left ventricle
Gomori trichrome stain
age related changes in Fischer 344 x brown Norway hybrid rats
Human studies are typically ______?
Cross-sectional
relationship between age and muscle area
-decline as age increases
advantages of longitudinal design?
many variables are standardized
-genetics, environment (to a extent) and diet (to an extent)
Centenarians
make up 0.02% of Canadian population
0.06% of Japan population
transgenic organism
an organism whose cell genome has been altered by the introduction of foreign DNA sequences
expected projection of centenarians to 2061
-continue to increase, by 2061 there will be many
-still will be primarily female, and some male
-both genders of this age group will increase too
Supercentenarians
> 110 years of age
approx 560 worldwide
-90% are women
the odds of living to >110 are 1 in 3 million
who was the oldest documented Human?
Jeanne Calment
122 years
-did fencing lessons at 85, she continued riding a bicycle, ate 2lbs of chocolate a week and quit smoking at 119
which sex has higher life expectancy?
female
- in older age groups there usually more women than men, once you get to 100+ they are almost all women
differences between women and men
women have a robust survival advantage over men, whereas men have a robust health advantage over women
-women display higher overall rates of physical illness
Tyrannosaur life tables
we are able to determine age, sexual maturity and mortality rate in non-avian dinosaur population
