Aging & Pigmentation Neuroendocrine

 Aging process is programmed into brain cells at birth

Aging
Definition
 Aggregate 总和 of structural changes and progressive
inability to sustain vital functions which eventually lead
to death
Supercentenarian
 Is someone who has lived to or passed their 110th
birthday
 Live a life typically free of major age-related disease
until shortly before maximum human lifespan is
reached
 Free of major age-related disease (stroke,
cardiovascular disease, dementia, cancer, Parkinson’s
disease and diabetes) until the very end of life when
they die of exhaustion of organ reserve, which is the
inability to return organ function to homeostasis
 Direct the process by means of hormonal / neuronal
influences
Immune dysregulation
 Decreased immunologic reactivity with age
 Leads to infections and neoplasia 肿瘤 in elderly
Free radical
 Accumulation of lipofuscin in cells
 Lipofuscin – derive from free radicals on plasma
membranes by lipid peroxidation
 Due to decreased antioxidant enzyme activity that
inactivate free radicals
Cumulative injury
 Aggregate effects of pathologic conditions sustained
during the life of the individual

Hypothesis of Aging
Programmed aging
 Reduced cellular mitotic division at a certain time
 Cells are programmed to make errors in transcription of
Nucleic Acid
 Defects in protein synthesis – lead to cellular
dysfunction – death

DNA damage
 Due to mutations or failure of DNA repair mechanism in
aging cells
 Cells carrying genetic damage will undergo apoptosis
or continues to grow as mutant cells leading to various
problem including cancer formation
Changes associated with aging
Oxidative stress and aging
- Cellular changes  Oxidative stress is the main reason of accelerated
 Cells are the basic building blocks of tissues senescence
 Free radials can result tissue degeneration by
 All cells experience changes with aging
damaging mitochondria genome and cause early
Cell loss
apoptosis (programmed cell death)
 As aging continues, waste products build up in tissue.
 Endogenous oxidative damage and repair systems
A fatty brown pigment called lipofuscin collects in many
play a big role in spontaneous mutagenesis
tissues, as do other fatty substances. Lead to cellular
 Mutated genes usually encode nonfunctional products,
degeneration and potential necrosis.
which disturb biochemical or/and signaling pathways
 Changes in metabolism lead to decreased cell size and
leading to more or less expressed pathological state.
number – cell loss leading to reduced organ mass –
(Cell die or become malignancy)
organ atrophy
 Free radials attack proteins and modify them. It usually
 Cell membrane changes, so many tissues have more
disturbs protein function and can accelerate the aging
trouble getting oxygen and nutrients and removing
process
CO2 and other wastes
Telomeres and aging
Organelle changes
 Telomeres are the terminal parts of eukaryotic
 Abnormal ribosome lead to abnormal protein
chromosomes
production and subsequent defective function of
 they are called "molecular clock" of the cell
cellular metabolism
 cell division times are correlated with telomere length
 Increased rate of organelle breakdown
 after each cell division telomeres get shorter
 Poor cytoskeletal microfilaments in macrophages lead
 when telomere shortens to the critical stage, the
to decreased phagocytosis
intensity of cell division significantly decreases, and
then cell differentiate and ages
DNA abnormalities
 telomeres are persistent in the not aging cells: cancer
 The result of a failure of cellular DNA repair mechanism
and germ line
 Lead to cell death or cell can behave abnormally
(cancerous)

Gerontogenes - Connective tissue changes

 Genes concerned with pathological aging = aging
genes
 When they are damaged organism ages much faster
 Genetic polymorphisms (genetic variation) that
involved in determining individual’s longevity are
reported. Thus, this factor influences the lifespan
between different populations.
Connective tissue changes, becoming more stiff. This
makes the organs, blood vessels and airways more
rigid.
Elastic tissue changes
a. Loss of cutaneous elasticity
- Produces cosmestic and structural consequences for
 aging skin - Hair changes
- The smooth appearance and fine wrinkles of aged skin
are associated with a gradual fragmentation of the  Thin, sparse 稀疏 and loses its pigment
elastic fiber network  Due to progressive failure of hair
 To produce keratin & pigment
b. Loss of elastic tissue in lungs
- The pulmonary system undergoes progressive
changes in mechanical properties with age which
ultimately compromise lung function and therefore - Reproductive system changes
diminish quality of life  Menopause
- In the aged lung, the loss of elasticity stimulates  Due to stop ovulation – decreased ovarian hormone
emphysema and plays an important role in increasing levels, atrophy of endometrial and reproductive system
the risk of mortality in the aging population as a result
of acute pulmonary diseases

c. Loss of vascular elasticity - Changes in host defense mechanisms

- The compliance and elasticity of the major arteries
plays a key role in cardiac function  Abnormal immune function – infections
- Age-related reductions in arterial compliance (known  Cause abnormalities such as pneumonia, autoimmune
as arteriosclerosis) play a major risk factor for the diseases and cancer
development of heart failure
- Can lead to vascular hypertension due to arterial
stiffening which is implicated as a major risk factor in
the development of strokes

Ground substances changes

- Lens – opacitities (cataract) – impair vision – increased
in diabetes patients
- Lens – loss accommodative power with age
- Visual changes – presbyopia (far-sightedness)

Cartilage and bone changes

- Osteoarthrosis – cartilage erosions
- Osteoporosis – loss of bone matrix and minerals –
thinning of bones
- Kyphosis – compression of vertebrae – decrease in
total height – if collapse – kyphosis