2. What is Ageing
Aging is the result of the progressive and irreversible decline of the
capacity of an organism to adapt to its ever-changing
environment.
Its multiple causes are all progressive, irreversible and harmful
ultimately leading to death
4. Cellular Ageing
Cellular Ageing is the progressive decline in cellular function
and viability caused by genetic abnormalities and the
accumulation of cellular and molecular damage due to the
effects of exposure to exogenous influences
6. Theories of Ageing
The knowledge regarding human ageing process is still obscure in some of its aspects
Many theories have been proposed to explain the process, but they are all specific of a
particular cause of ageing; a global view of them is needed
8. Evolutionary theory
• Accumulation of DNA mutations after several cell
cycles leads to cessation of further division
Mutation Accumulation
• Result of natural degrading process that leads to
accumulation of damage which can be repaired at the
expense of reproduction
Disposable soma
• Some traits that increase fitness early in life may also
have negative effects later in life.
Antagonistic pleiotropy
9. Molecular Theory
GENE REGULATION: Ageing is caused by changes in expression of genes regulation
CODON RESTRICTION: Accuracy of mRNA translation is impaired due to inability to
decode codon in mRNA.
ERROR CATASTROPHE: Decline in correct gene expression results in increased
fraction of abnormal proteins..
SOMATIC MUTATION: Molecular damage accumulates due to DNA damage.
DYSDIFFERENTIATION: Gradual accumulation of molecular damage impairs gene
expression. regulation.
10. Cellular Theory
TELOMERE THEORY : Senescence results from telomere loss with each cell cycle.
FREE RADICAL THEORY : Oxidative mechanisms produce highly reactive free
radicals that subsequently damage proteins, lipids, & DNA.
WEAR & TEAR THEORY : Accumulation of normal injury leads to senescence.
APOPTOSIS : Programmed cell death from genetic events or genome crisis
11. Systemic Theory
• Alterations in neuroendocrine control of
homeostasis results in ageing
NEUROENDOCRINE
• Assumes a fixed amount of metabolic period
for every living organism. (LIVE FAST, DIE
YOUNG)
RATE OF LIVING
12. Theories of Ageing
The search for a single cause of ageing has recently been replaced by the view of ageing
as an extremely complex, multifactorial process.
Therefore, the different theories of aging are not mutually exclusive, but complementary
of others in the explanation of the normal aging process
18. DNA Repair and Senescence
Monitors integrity of
DNA before replication.
Pauses cell cycle
for DNA repair
G1/S
Monitors integrity of
DNA after replication so
that it can enter mitosis
DNA damaged beyond repair
Non-replicative state
(SENESCENCE)
G2/M
19. Telomeres
Cellular Senescence: Normal cells have a limited capacity for replication. After a fixed no. of
divisions cells become arrested in a terminally non dividing state, known as replicative
senescence
Chromosomes end with repeats of conserved ‘TTAGGG’ sequence - interact with specific
proteins -looped conformation- protects chromosomal DNA from degradation
23. Defective Protein homeostasis
Maintenance of protein quality, or proteostasis, is critical for the health and
longevity of the cell
Proteostasis ensures a supply of high-quality protein by culling misfolded and
damaged proteins from the cellular pool and replacing them with newly formed
proteins
Disruption of proteostasis is hastened by stress and signals organismal ageing
24. Chaperones, include small heat
shock proteins, as well as SOD
and catalase
direct AA chains to the correctly
folded state, misfolded proteins
to degradation pathways &
refold misfolded proteins
UPR monitors quality of
unfolded AA chains primarily in
the ER: ER-associated
degradation (ERAD) pathway
.
Molecular chaperones
25. Autophagy-Lysosome
System
► Autophagy is required for
longevity
► Inhibition of autophagy
generates hallmarks of aging at
an accelerated rate
► Autophagic clearing of
damaged proteins, protein
aggregates, organelles, lipids,
etc is required to provide new
raw material for a healthy cell.
26. Nutrient Sensing
Dietary restriction (DR), a reduction in food intake without malnutrition, extends the
average and/or maximum life span of various organisms
Causes a reduction in metabolic markers of several diseases, including diabetes,
cardiovascular disease and cancer increasing longevity
27. Insulin and insulin-like growth factor(IIS)
Caloric restriction
- “insulin and insulin-like growth factor”(IIS)
leads to increased life span and resistance to age-related pathologies
- Ribosomal S6 protein kinase 1 (S6K1)
RAS
FOXO, a transcription factor
- mammalian Target of Rapamycin
serine/threonine-protein kinase
AKT
28. Sirtuins
Sirtuins are a family of proteins that act as NAD(+) dependent histone deacetylases, which help
control gene expression coding for various proteins
Sirtuins detect when energy levels are low by sensing the coinciding increase of NAD+.
They also
help control catabolic metabolism
stimulate protein folding
inhibit harmful effects of ROS.
Upregulating sirtuins produces anti-aging or health-promoting effects
30. Disorders of Premature Ageing
HUTCHINSON GUILFORD PROGERIA
Male pattern baldness
Cataracts
Life span :10 yrs.
Mutation in LMNA gene (codes for protein Laminin A)
Defective precursor (PROGERIN)
Interferes with organisation of nuclear heterochromatin
which regulates expression of various genes
31. Disorders of Premature Ageing
ATAXIA TELENGIECTASIA
Manifestation of ageing at increased rate.
Mutation in gene encoding for protein involved in repairing double
stranded breaks in DNA.
32. Premature Ageing Disorders
DOWN’S SYNDROME
Patients generally age more rapidly.
Their fibroblasts are capable of fewer cell divisions in culture than those
from age matched controls.
The loss of telomeres was shown to be more rapid in lymphocytes
isolated from the blood of trisomic patients in accord with their more
rapid aging.
33. A list of syndromes carrying defect in genome maintenance
34. A list of syndromes carrying defect in Genome Maintenance
38. SENESCENCE –POSITIVE ASPECT
Senescence functions as a tumour suppressing
mechanism limiting cell proliferative capacity in vivo
implying that replicative senescence did not evolve to
cause ageing but is rather a consequence of a biological
device that suppresses tumour formation.
