Biology of Aging Quiz

Ageing: Theories and Disease

• Ageing is defined as a decreasing ability to survive
• Key factors of ageing include: reduced ability to work, increased susceptibility to major diseases, and a large health care commitment
• Life expectancy is the mean age of individuals at the time of death.

Ageing: Terminology

• Lifespan is the maximum age that a species can attain.

Estimates and Projections of the Total Population in the United States and the Percentage of Elderly, 1900-2030

• Data shows the total population and the percentage of people over 65 in the United States from 1900 to 2030. Projections are included.

Percentage of Elderly in the U.S. Population by Age Group

• Data shows the percentage of the population for age groups 65-74, 75-84, and 85 and above, from 1960 to 2040.

Features of Ageing

• Senescence
• Age-related disease

Senescence Changes

• Senescence may cause age-related disease
• Senescence may increase susceptibility to disease

Theories of Ageing: Wear and Tear

• Free radicals
• Glycation
• Waste products
• Error-catastrophe

Free Radical: Definition

• An atom or molecule that contains one or more unpaired electrons

Free Radicals: Nature

• High reactivity
• Short half-life
• Propagate chain reactions

Type of Free Radicals

• Hydroxyl radical (OH-)
• Superoxide radical (O2-)
• Nitric oxide (NO)

Sources of Free Radicals

• Phagocytic cells
• Ionising radiation
• Smoking
• Oxidation-reduction reactions
• Hyperglycaemia

Free Radicals Damage

• DNA/RNA damage
• Protein damage
• Enzyme damage
• Membrane lipid damage
• Cell damage

Antioxidant: Definition

• A substance that will delay or inhibit the oxidation of an oxidisable substrate

Types of Antioxidants

• Extracellular: Vitamin E
• Intracellular: Superoxide dismutase, catalase

Superoxide Dismutase: Action

• Superoxide dismutase converts superoxide radicals to hydrogen peroxide and oxygen. Catalase then converts hydrogen peroxide into water and oxygen.

Free Radicals in Ageing

• Increased free radical damage with age
• Decreased antioxidant defences with age

Free Radicals in Ageing: Biomolecules

• Damage to biomolecules may occur.
• Defense mechanisms like antioxidants aim to prevent or repair damage.

Free Radicals in Ageing: Outcomes

• Biomolecule damage can lead to cell death, aged cells, or cancer.
• This leads to a decline in tissue and organ function, as well as age-related pathologies, and in the end, death.

Protein Glycation

• The elderly are susceptible to protein glycation due to decreased glucose tolerance and increased rates of diabetes.

Glycation of a Protein

• Glycation involves the attachment of glucose to a protein. This forms a Schiff base, Amadori product, and eventually advanced glycation endproducts, or AGEs.

Effects of Glycation on Proteins

• Increased cross-linking
• Increased fluorescence
• Altered enzyme activity
• Altered immunogenicity
• Altered half-life
• Altered receptor recognition

Accumulation of Waste Products

• Lipofuscin is a lipid-rich pigment produced due to the byproducts of free radical peroxidation.
• Effects of lipofuscin are unknown

Error-Catastrophe Theory

• Abnormal proteins are produced due to DNA transcription and translation errors.
• Accumulation of abnormal proteins impairs cellular function.

Theories of Ageing: Genome Based

• Programmed ageing
• Mutations

Programmed Ageing

• Number of cell divisions is fixed (Hayflick limit)
• Limit not affected by external environment
• Cells can memorise undertaken divisions.
• Telomeres shorten, limiting cell division. Telomerase can extend cellular division.

Gene Mutations

• Errors in DNA replication that are not repaired affect cell viability.
• DNA repair systems decrease with age.

Multifactorial Nature of Ageing

• Ageing is influenced by genetics, lifestyle factors, and environment. These lead to a rate of ageing, which gives rise to age-related diseases.

Declines in Various Human Capacities With Age

• Data on various human capacities decline/reduction percentage with age, from 60 and 80 years old compared to 30.

Cellular Ageing

• Decline in mitochondrial activity
• Decline in oxidative phosphorylation
• Decline in DNA/RNA processes
• Decline in nutrient uptake
• Decline in chromosomal repair
• Accumulation of waste products
• Changes in organelle shapes

Immune System

• Decrease in antibody production
• Decline in T cell function
• Atrophy of thymus and
• Increased in autoimmune reactions

Skin

• Increased wrinkling
• Skin pigmentation
• Greying of hair
• Loss of hair
• Delayed wound healing

Lungs

• Decrease in lung size
• Decrease in lung elasticity
• Reduced gaseous exchange
• Reduced capacity for strenuous work

Cardiovascular System

• Increased rigidity of blood vessels
• Arterial calcification and hardening
• Increase in blood pressure
• Accumulation of fibrous tissue in heart muscle
• Reduced cardiac output
• Reduced blood supply to tissues

Kidneys

• Decrease in kidney weight/volume
• Loss and replacement of nephrons with scar tissue
• Reduced renal filtration rate
• Reduced elimination of waste

Liver

• Reduction in liver size and hepatocytes
• Decline in liver functions (e.g. drug detoxification)

Muscles

• Muscles undergo atrophy
• Decreased capacity for work

Endocrine System

• Decline in hormone production
• Decline in hormone receptors

Brain

• Loss in weight
• Loss of nerve cells
• Increase in amyloid deposition
• Accumulation of lipofuscin

Eye

• Decreased ability of lens to change shape
• Increased cross-linking and browning of lens protein

Body Composition

• Decrease in muscle mass
• Increase in total body fat

Progeria (Hutchinson-Gilford Syndrome)

• Disorder characterized by accelerated ageing.
• Affected children age approximately 10 times faster than a normal human being.

Progeria: Incidence

• Very rare
• Reported cases globally are few
• Reported cases across all history is also limited

Progeria: Aetiology

• Sporadic dominant mutation.
• Reduced life-span of cells
• Reduced DNA repair of damaged DNA.

Progeria: Clinical

• Thinning / wrinkling of skin
• Alopecia
• Loss of subcutaneous fat
• Prominent veins on the scalp
• Beak-like nose
• Characteristic squeeky voice
• Short stature
• Arthritis
• Osteoporosis
• Normal/high intelligence
• Delayed development

Progeria: Features compared to Ageing

• Presents with multiple characteristics across various bodily systems
• Presents with several physical features that distinguish it from the normal ageing pattern.

Progeria: Outlook

• Average lifespan is approximately 13 years
• Death often results from coronary heart disease or stroke

Progeria: Diagnosis

• Difficult due to rarity.
• Insidious onset
• Elevated urinary hyaluronic acid

Progeria: Management

• No cure for progeria
• Education/psychological support
• Medications to relieve symptoms of the condition

Calorie Restriction

• Only known method of slowing aging in mammals.
• Reduced calorie intake: extends lifespan and delays age related diseases.

Calorie Restriction: Examples

• Found effective in extending life spans in numerous species such as protozoa, spiders, water fleas, chickens, and rhesus monkeys.

Calorie Restriction: Effect

• Reduces age-associated mutations
• Reduces free radical damage
• Reduces advanced glycation endproducts

Anti-ageing Therapy

• Aim to make ourselves younger for longer, instead of ageing for longer.

Anti-ageing Therapy Companies

• Centagenetix
• Elixir
• Eukarion
• Alteon
• Geron Corporation

Centagenetix

• Seek genes responsible for longevity.
• Collect DNA from people with long lifespans, and identified a gene on chromosome 4
• Develops compounds to mimic proteins coded by genes.

Elixir

• Study nematode worms with multiple copies of genes SIR2. SIR2 enhances lifespan during caloric restriction.
• Identify longevity genes for anti-ageing medications.

Eukarion genetically engineering

• Mice engineered to lack superoxide dismutase
• Superoxide dismutase aids lifespan due to oxidative damage

Alteon

• Develop drugs to reduce AGEs (advanced glycation endproducts)
• Previous unsuccessful trial with aminoguanidine.
• Anti-glycation drugs

Geron Corporation

• Telomerase protects telomeres at the ends of chromosomes
• Drug that switches off telomerase in cancer cells.
• Drug that switches on telomerase to protect telomeres and extend lifespans.

Essential Reading

• Ahmed et al (2007): Biology of disease
• Taylor & Francis book, specific pages 515-530.

Conclusion

• Ageing, caused by wear and tear processes, is influenced by genes.
• Ageing leads to senescence and heightened susceptibility to diseases.
• Potential future anti-ageing therapies have positive influence.