Article 2: Horizons in the Evolution of Ageing (Flatt, Partridge)

Question 1

The evolution of ageing in humans

Answer 1

• Lifespan increase: 2,5 years per decade in last 200 years
• More ppl with cardiovascular diseases, more ill old
• Demographic change

Question 2

Why does ageing evolve?

Answer 2

• Some species do not age
• Population genetic theory of ageing:
mutation accumulation: e.g. Huntingtons disease, onset at 35
antagonistic pleiotropy: selection can favor mutation with positive effets even though they may be negative in later life, e.g. cellular senescence
• Disposable soma hypothesis
• Fruit fly experiments: trade-off between life-span and fitness
• MA and AP maybe both play role
• Medawar+Williams: low extrinsic mortality= evolution of low intrinsic mortality and vice versaage dependent
• Aging= non-adaptive side effect of the declining ability of selection to maintain fitness at older age
• Ageing=genetically complex trait

Question 3

Some mechanisms of ageing are evolutionary conserved

Answer 3

• Ageing in laboratory  highly malleable to simple genetic, environmental and pharmacological interventions
• Evolutionary conversation (amelioration of ageing) through:
Dietary restrictions (DR) -> induces mechanisms for surviving food shortages
sensing nutritional status through insulin/insulin-like growth factor signaling (IIS) and the target of rapamycin (TOR) network  genetically reduced activity of IIS/TOR can increase lifespan (worm and mouse)
• Rapamycin (drug) targets ISS/TOR network, can increase lifespan
• Insulin-like growth factor-1 (IGF-1) signaling mediates physiological life-history variation in mammalian populations
• Naturally segregating polymorphisms in IIS have been linked to latitudinal gradients (clines) in life-history traits
• Some natural alleles of insulin-like receptor gene have pleiotropic effects upon lifespan, stress resistance, fecundity, and body size
• Quantitative trait loci affecting gene expression (so-called eQTLs) in fruit flies  IIS variants that affect transcription in response to dietary change
• In social insects (e.g. honeybees), ISS/TOR has physiological and developmental effects on caste development, foraging behavior and probably longevity
• Contradictory to Williams no single mechanism responsible for ageing?
• Phenotypic plasticity: ability of a single genotype to produce different phenotypes in response to changes in the environment
• Role of IIS/TOR network in ageing may represent optimization of mechanisms of phenotypic plasticity

• IIS/TOR not always identified as longevity genes
• Increased inflammation is major feature of ageing process

Question 4

Is ageing universal? Diverse patterns of senescence among species

Answer 4

• No ageing: freshwater polyps, many plants BUT might not be studied enough
• Many reproduce before reaching full body size
• Ageing might not be universal
• Ageing phenomenon of soma, only in organism that have distinction between parents and offspring
• Naked mole rat longest living rodentmortality ate does not grow with age

Question 5

Trade-offs with lifespan are pervasive but can be uncoupled

Answer 5

• Phenotypic trade-offs in bats: AP/DS hypothesis
• More offspring, faster ageing
• Might also be uncoupled  laboratory environment
• Uncoupled ant queen
• Algae division of labor=general principle underlying decoupling of trade-offs
• Germline and soma
• Longevity can be reached without the cost of reproduction
• Laboratory vs. real life
• Rapamycin, metformin
• Removal of senescent cells, stem cells, microorganisms in gut

Question 6

Key lessons from the evolution of ageing

Answer 6

• Not a programmed process, high level regulators of phenotypic plasticity are able to change effects of ageing, physiology
• Amelioration of ageing can protect against multiple types of loss of function/age related diseases (if shake off of trade-off)
• Some animals live very long still not sure why
• Some species don’t age at all good for research