The document discusses senescence and aging at the cellular, organismal, and population levels. At the cellular level, senescence refers to a cell losing its ability to divide over time due to factors like telomere shortening and oxidative damage. Organismal senescence is characterized by a decline in fertility and increased mortality risk with age. Population studies of senescence examine age-specific survival and mortality rates using life tables to analyze factors influencing life history strategies. The genetic basis of senescence is complex, with multiple genes and environmental influences contributing to the aging process.

2. The evolutionary genetics of senescence
The word senescence is drived from the latin word meaning ol
It is the change in the biology of an organism as it ages after its maturity.
Senescence is a program in which the function of an organ or whole part of the organism
naturally declines to death.
It is a process caused by deterioration in molecular and physiological function.
 This deterioration increases an individual’s probability of mortality and decreases its
likelihood of successfully reproducing.

3. Cont..,
Senescence in animals can be characterized as a “progressive loss of fertility and increasing
probability of death with increasing age”(Medawar, 1946, Comfort, 1956, Kirkwood & Austad,
2000).
from the population perspective: senescent populations present increasingly higher death rates
with increasing age (Masoro & Austad, 2006).
senescence associated frailty/unfitness causes population death rates to rise exponentially with age
(Gompertz, 1825).
Senescence is a clearly deleterious process, which seems difficult to conciliate with natural
selection, which predicts evolution towards increasing fitness.

4. Cont..,
Historically, the first evolutionary explanation able to conciliate these two processes is known
as the (Medawar, 1952).
According to mutation accumulation theory,
in age-structured populations the force of selection decreases with increasing age,
allowing the accumulation of deleterious genes with age-specific effects on mortality rate.
Under population genetics mechanisms,
senescence is not necessarily deleterious: the original Medawar’s proposition implies that
the interruption of age-specific effects of harmful genes is equivalent to their elimination
in such a way that they become effectively neutral.
Hence, such interruption is beneficial and senescence can be regarded as a side effect of

5. Cont..,
Although a number of evidences have since been collected in support of each of these
theories, in the last decades some phenomena have challenged all of them.
 This includes
the effect of caloric restriction on longevity,
the late-life mortality deceleration and
the longevity pathways controlled by either a single or a few genes, such as
• the insulin pathway and
• the effect of sirtuins on longevity.
Generally, senescence is the process by which a cell loses its ability to divide, grow,
function.
 this loses of function ultimatly end in death.

6. Cellular senescence
Cellular senescence is the phenomenon by which normal deploid cells lose its ability to divide
normally after about so cell divisions in vitro.
some cells become senescent after fewer replication cycles as a result of DNA double strand breaks.
this phenomenon is also known as replicative senescence also called Hayflick phenomenon.
in response to DNA damage (including shortened telomers) cell either age or self destruct
(apoptosis programmed cell death) if the damage can not be easily repaired.
 in this cellular suicide, the death of one or more cell may benefit the organism as a whole.
• for example: in plant the death of the water conducting zylem cell (tracheids and
vessle elements allow the cell to function more efficiently and so driver water to the
upper part of the plant.

7. Cont..,
Plant exhibits various type of organs and in response to many different stimulant.
many annual plants eg. wheat, maize, soyabean, aptuptly yellow and die following grain
product.
senescence of the entire plant after sigle reproductive cycle is know as monocarpic
senescence.
aging can be defined as the time related deterioration of the physiological function
necessarly survival and fertility.
the ageing process has two major facts.
 the first is simply concerned with how long an organism lives
the second is concerned with the physiological deterioration or senescent, that characterize old age.

8. Theory of senescence /aging
traditionally aging was explained two theories.
1. implies that aging is regulated by biological clock operating
throughout the lifespan.
this regulation would depend on change in the gene expression that affect the system
responce for maintainance.
2. - it blame environmental impact on living organisms that induce
commulative damage at various levels as the cause of aging.

9. Genes responsible for senescence
There are a number of genes responsible for the senescence of the organism. these are;
1. :- responsible for down regukation of insulin signaling and cause progeria.
Progeria:- is a pre matured aging syndrom in human that appears to be caused by
mutation in DNA repair enzyme
2. :- important regulation of cell division, stops cell cycle causing cell senescence, provide
protection againest cancer (guardian of the genome).
3. - encode histone deacetylation enzymes and blocks chromosomal rearrangment
Sirtuin protiens pervent aging.

10. According to there are over 700
genes associated with aging in model organism. Among these;
padospera saccharomyces caenorhabditis Drosophila Mus
Grisea LAG1 daF2 sod-1 prop-1
LAC1 age1/daf23 cat-1 melk-1
Pit1 Ghe mth
RAS1 akt1/akt2
PHB1 daf16
PHB2 daf12
CDC7 old-1
BUD1 spe-26
HDA1 clk-1
SLR4-42 mev1
UTH4
SGS1
RADS2
FOB1

11. Senescent morphology
senescence cell become flattened, have increased Beta-galactosidase activities.
 Increase size of nucleus and nucleoli.
increase number of multincleated cell
increase number of lysosomes, golgi and cytoplasmic microfilaments.
Markers of a senescent cell
P16 expression
heterochromatic foci damage
Telomer DNA damage
DNA damage foci

12. Factors responsible for senescence
There are a number of factors responsible for the senescence of the organism. these are;
Replicative exhaustion/ telomer shortening/
Oxidative stress
Direct DNA damage
Oncogenic activation

13. Telomer and senescence
Telomer shortening cause cell senescence.
 somatic cell usually lack telomer activities => which means that telomers shorten with
each cell diviusion.
cell may go into crisis as the result of reaching zero telomer length.
reactivation of telomerase enables cell to survive crisis and to be immortal.
eroded telomers generate a presistent DNA Damage Response (DDR), which initiates
and maintains the senescence growth arrest.

14. Oxidative Stress and senescence
Oxidative mechanisms produces highly reactive free radicals that subsquently damage
protien and DNA.
 oxygen free radicals generate/cause cummulative oxidative damage, thus resulting in
• structural degeneration apoptosis.
• functional decline
• age relatec diseases
Evidences from Model organisms
supper oxidative dismutase (SDS) transgene can extend the lifespan of Drosophila
pre-oxidase activity can extend C.eleganas lifespan

15. Oncogene activation and cell senescence
cellular senescence is an important tumour suppressor mechanisms.
 the senescence response may be an example of the evolutionary antagonstic pleiotropy.
• antagonstic pleiotropy rests on the fact that are replete with final extinict hazareds
the age-related increase in senescence cells occure in metotically competent tissues, which
give rise to cancer.
 inactivation of tumour suppreser genes encoding P53 and PRB protien.
P53 and PRB protien:- control expression of other genes,
• that halt cell cycle progression in response to inducer of senescence
• response to senescent signals and
• allow normal cells to sense

16. Cont..,
mutations that dompen cellular greatly increase susceptibility to cancer.
Progeria:- is a pre matured aging syndrom in human that appears to be caused by mutation in
DNA repair enzyme
in human Hutchinase-Gilford progeria is a rapide aging syndrome.
 children born with this condtion age rapidly (usually of heart failure) as early as 12 years
of age.
• Hutchinase-Gilford progeria is the result of a dominant mutation in the gene that
encodes lamin A, a nuclear membrane protien and these some mutation can be seen
age related senescence
• symptom: all the symptom are characterized by human senescence phenotype. eg.
skin with age spots, resorbed bone mass, hair lose, arterios cleroosis, etc.

17. Genetic architecture refers to the genetic basis of a phenotypic trait.
Beyond comprehending the map of the genes linked to a given trait, genetic architecture
considers all phenomenon through which such genetic map produces the phenotype (Masoro
& Austad 2006).
The most common definition of the senescent phenotype combines individual effects
(decrease in functional and reproductive abilities) with an effect which is measurable only in
a population (age-dependent increase in mortality).
This often leads us to conclude that it is exactly the same phenomenon that makes us
individually more fragile and at greater risk of dying as we age.

18. Cont..,
There are three different models for the relationship between physiological and
demographic senescence on the genetic architecture of senescence.
(a) Genes negatively influence physiological processes, which, then, lead to increasing
effects on age-specific mortality.
(b) The same genes that lead to physiological senescence independently lead to increasing
age-dependent death rates, which are demographically measurable.
(c) Different genes operate over physiological and demographic processes that are linked
with senescence.

19. Cont..,
some genetic phenomena that may have importance for the genetic architecture of senescence.
Such phenomena include:
• Epistasis, when the expression of a gene negatively influences the expression of one another;
• Polygeny, where multiple genes contribute to a phenotypic trait;
• Pleiotropy, when multiple phenotypic characteristics are influenced by a single gene;
• Plasticity/physical, when a single genotype can produce more than one distinct phenotype, such
phenotypic diversity may occur among individuals of the same genotype, by action of different
environmental influences on the same individual or in the same individual at different ages; etc.

20. Cont..,
Epistasis could function similarly to what is predicted on antagonistic pleiotropy theory:
 assuming two genes with positive effects for fitness, in which the first gene exerts a
negative effect on the expression of the second gene, the first gene would have positive
and negative effects on fitness.
 The effect under selection, however, would be the average effect.
It is believed, since the formulation of the theory of mutation accumulation by Medawar, that
senescence is a polygenic phenotype (Medawar, 1952).
Indeed, recent decades have seen the description of “hundreds of aging genes” (Promislow et al.,
2006).
 Summed to the fact that senescence is an early onset and gradually progressive phenotype in almost
all of the species that has been described, it points to a polygenic inheritance with almost-continuity
in organic response to genes that determine senescence.

21. In practice, can be hard to identify a population; often a study area is defined and this defines
a ‘study population’.
Care is needed when a population is defined in this way, b/c immigration and
emigration can affect estimates of survival and reproduction.
2. Population size and geographic extent vary through time
3. Definition cannot be applied to asexual organisms - for these, the focus is on proximity
is a group of individuals of the same species, living sufficiently close together,
intermating is possible, and therefore sharing a common gene pool.
Study of population parameters is also called , from Greek root for population, ‘deme’.

22. Cont..,
Population-level variables depend on the properties of individuals that compose the
population.
The two most basic parameters of a population are an individual’s likelihood of surviving
and an individual’s likelihood of breeding.
A quick glance at the world reveals that both of these depend on the individual’s age, in most
species.
E.g. very young and very old individuals often don’t breed, and very young individuals
often have high odds of dying.

23. Cont..,
 These basic parameters are combined in a life-table, as and
. From these two parameters, we can derive considerable
information, which falls into two categories:
1. Demographic information allows measurement of the rate of population growth and
projection of future population sizes.
2. Demographic information allows analysis of ‘life-history tactics’.
 For example, some species breed once and die, while other breed many times.
Some species mature quickly while others wait years before reproducing.
Demographic data allows quantitative analyses of the fitness trade-offs involved in the
evolution of life-history tactics.

24. Cont..,
Many life-history processes are continuous, but are
broken into discrete units for the purpose of demographic analysis.
Example is aging. Age is a continuous variable, but it is generally broken into discrete
age-classes in demographic analyses.
As long as the discrete units are not too long, this approach usually works well.
 E.g. most vertebrates have a distinct annual breeding seasons, so life-tables for
vertebrates are based on discrete one-year age-classes, each potentially including a bout
of reproduction.

25. Cont..,
First step in life table is determining age-classes to be used. Age class (x) is the first
column of life table.
escribes the probability of surviving through each age class.
 it can be determined in two basic ways.
1. is to observe a set of individuals through time, from birth to death,
recording how many still alive in each age class (at beginning of class usually, but can
also be at mid-point of age class).
 E.g. Start with 500 newborns. N0 = 500. 400 still alive at age 1, so N1 = 400.
200 still alive at age 2 so N2 = 200. Continue until all are dead, Nω = 0.
• ω (omega) is typical symbol for oldest age attained.

26. Cont..,
is to record individuals of each age class present in population at
one time. N0 = 500 juveniles, N1 = 400 1-year olds, N2 = 200 2-year olds, etc.
 Survivorship from birth to age-class x, is denoted lx. (l for life)
lx = Nx/N0 (N for number)
 This is the likelihood of living to a given age. Interesting for some questions, but for
 others we want to know the probability of dying during a specific age-class, or sx.
Age class x Number in age class: Nx Survivorship from birth: lx Age-specific survival: sx
0 500 1 0.80
1 400 0.80 0.50
2 200 0.40 0.25
3 50 0.10 0.00
4 0 0.00 -----

27. Cont..,
Age-specific survival is denoted Sx. (s for survival)
Sx = Nx+1/Nx (= lx+1/lx) ; Nx= number in age class; lx =Survivorship from birth:
lx decreases continually through age classes, but this does not mean that old animals are
more likely to die than young animals.
 Use Sx values to compare the risk of death for different age classes.
But need to use lx to ask questions about benefit of reproducing at different ages
(because it is lx that determines whether an individual will be alive to reproduce at a
given age).

28. Cont..,
Survivorship curves: three general types are often described (Deevey 1947), based on shape
of log-linear plot of Nx vs x.
1. Type II is a straight line: constant probability of death (birds)
2. Type I: survive well until senescence (large mammals, humans)
3. Type III: heavy juvenile mortality (inverts, fish, plants)
Though these types are useful descriptors, real survivorship curves are often more complex
in shape, and there are MANY exceptions to the general pattern.
Knowing the types is useful, but it is not safe to assume (for example) that a bird population
will have type II survival.

29. Cont..,
For example, mammals are often said to have Type I survival, but many mammals also have big
pulse of mortality among juveniles,
Other mammals have Type II constant mortality, as in dwarf mongooses:
Good example of practical problems with measuring lx comes from fish, where differences in
catchability of age-classes makes early survival almost impossible to measure in ordinary ways.
Survivorship (lx) tables can be used to calculate life expectancy, Ex, which is the average
lifespan remaining for an individual of age x.
𝐸𝑥 = 𝑦=𝑥
𝜔 𝑙𝑦/𝑙𝑥
E0 = (1 + 0.80 + 0.40 + 0.10)/1 = 2.30 years
E1 = (0.80 + 0.40 + 0.10)/0.8 = 1.63 years

30. Cont..,
mx = 1/2 number of offspring born to parent of age x.
For each offspring produced, male and female parent each credited with 1/2 of an offspring
produced.
To see the logic of this, remember that in sexual organism, each individual must leave 2 offspring
for exact replacement.
In practice, mx is usually measured as female offspring per female of age x (m for maternity).
This is simply because paternity is usually unknown, so numbers of offspring per male can’t be
measured.
In some cases, male reproduction is known, and mx is measured as 1/2 of total offspring for each
parent.

31. Cont..,
It referes the total lifetime reproduction in the absence of mortality.
This is the average lifetime reproduction of an individual that lives to senescence, useful
in considering potential population growth if all ecological limits such as;
 predation,
 competitors,
 disease,
 starvation were removed for a population.
GRR is rarely if ever attained in nature, but useful to consider how far below this a
population is held by ecological limits.

32. Cont..,
Average number of offspring produced by an individual in its lifetime, taking normal
mortality into account.
lx is the odds of living to age x, mx is the average of kids produced at that age, so the
product lxmx is the average number of kids produced by individuals of age x.
Summed across all ages, this is average lifetime reproduction.
R0 < 1 individuals not fully replacing themselves, population shrinking
R0 = 1 individual exactly replacing themselves, population size stable
R0 > 1 individuals more than replacing themselves, population growing

33. Cont..,
The schedule of reproduction (mx curve) can be used to determine the generation time, T.
hich breed only once in life (e.g. salmon,
many insects)
T = egg to egg time, or newborn to newborn time (obviously).
T is more complex.
To understand this, think first about the numerator. lxmx is the average number of offspring
born to female at age x, as discussed above.
 If we weight each offspring by the age of the mother, x, and then sum across all ages, then we
have the mother's age when each offspring was born, summed across all offspring born in her
life

34. Cont..,
X Nx lx mx lxmx xlxmx
0 500 1 0 0 0
1 400 0.80 2 1.6 1.6
2 200 0.40 3 1.2 2.4
3 50 0.10 1 0.1 0.3
4 0 0.00 0 0.0 0.0

35. Cont..,
The denominator (Σlxmx) is equal to the total number of offspring born.
Dividing the numerator by the denominator gives the mean age of a female when each of her children was born.
In other words, the whole expression is just a weighted average if most offspring are produced when mothers
are young, T will be short; if most offsrping are produced when mothers are old, T will be long.
The denominator is equal to R0.
In a stable population, R0 = 1, so the denominator has no effect on generation time.
In a growing population, R0 > 1 and T is decreased, because it takes less time for a cohort to ‘replace’
itself.
In a shrinking population, R0 <1 and T is increased, because it takes longer for a cohort to ‘replace’
itself.

36. Age structure reflects the proportions of individuals at different life stages.
This variable is an important indicator of population status.
Growing populations generally have
Whereas declining populations usually have
Stable populations usually have relatively more individuals in reproductive age-classes.
However, populations with larger proportions of individuals in younger age-classes also may
reflect low survivorship in these age classes,
whereas populations with smaller proportions of individuals in younger age-classes
may reflect high survivorship.

37. Age structure
The effects of age structure on population dynamics are most obviously manifest in
population productivity through effects on individual
fertility,
fecundity, and
probability of raising a time of life to weaning or recruitment.
Telomere damage, epigenetic dysregulation, DNA damage, and
mitochondrial dysfunction can induce senescence.