Nutrition and Ageing Flashcards
Define aging
time-depedent, gradual, progressive deterioration
Hallmarks of Aging
Altered Intercellular Communication
Genomic Instability
Telomere attrition
Epigenetic Alterations
Loss of Proteostasis
Deregulated nutrient-sensing
Mitochondrial Dysfunction
Cellular Senescence
Stem Cell Exhaustion
Genomic instability
Overtime DNA damage occurs from:
Exogenous sources (UV & chemicals)
Endogenous sources (ROS & spontaneous mutations)
- DNA repair mechanisms repair much of the damage, however not 100% efficient
- DNA damage accumulates -> decreased cell function and diseases
Epigenetic Alterations
- includes changes to acetylation and methylation at both DNA and the histone level, impacting the expression of many genes
- theoretically reversible
Telomere Attrition
- telomeres are protective caps at ends of chromosomes made from repeating DNA sequences
- each time a cell divides, the telomeres get shorter
- telomerase builds them back up but this decreases with aging
- cells that divide too many times become senescent when telomere length becomes too short
Loss of Proteostasis
- protein homeostasis
- effectiveness gradually decreases leading to a buildup of dysfunctional proteins
- chronic accumulation of incorrectly folded proteins is thought to play a role in Alzheimer’s and Parkinson’s disease pathologies
Deregulated Nutrient Sensing
- anabolic signalling pathways (insulin & IGF-1) appear to enhance aging while inhibition via caloric restriction or fasting have shown in animal studies to delay aging
- human research is lacking
Mitochondrial Dysfunction
- progressive mitochondrial dysfunction due to factors including accumulation of mtDNA damage
- results in decreased ATP synthesis and increased ROS production
- ROS at high levels increase aging associated damage
Cellular Senescence
- irreversible cell cycle arrest (stop dividing but dont die)
- results from telomere shortening & the accumulation of genetic damage
- accumulation of senescent cells which are less functional therefore reducing tissue function & contribute to the increasing inflammation associated with aging, by secreting pro-inflammatory cytokines (inflammaging)
Stem Cell Exhaustion
- attrition in adult stem cells
- e.g. decrease in hematopoietic stem cell’s (HSCs) -> decreased immune function, termed immunosenescence
- results in decline in the regenerative potential of tissues
- drivers include accumulated DNA damage and telomere shortening
Altered Intercellular Communication
- Ageing involves changes that impact endocrine,
neuroendocrine and neuronal communication
between cells - ntercellular communication
pathways such as the renin-angiotensin,
adrenergic and insulin-IGF1 signaling tend to be
deregulated - increased inflammation, immune system changes
and changes to the extra cellular environment play
roles - “Inflammaging
- Sirtuins
may also have an impact on age-associated
inflammatory responses
Primary hallmarks - Causes of damage
genomic instability
telomere attrition
epigenetic alterations
loss of proteostasis
Antagonistic hallmarks - responses to damage
deregulated nutrient-sensing
mitochondrial dysfunction
cellular senscence
integrative hallmarks - culprits of the phenotype
stem cell exhaustion
altered intercellular communication
_______ are nicotinamide adenine dinucleotide (NAD+)-dependent
lysine deacylases that promote longevity and healthy ageing
Sirtuins
Sirtuins
- impact on metabolic function & longevity
- STAC’s bind to and modulate SIRT1 for NAD+ & protein -> increased activity
- increasing NAD+ -> enhance activity of sirtuins -> improve metabolic function & increase longevity
- sirtuin overexpression & treatment with natural & synthetic STACs -> improves metabolic function and increases longevity in mice
NAD+
- supplements & efficacy
- requirements can be met through intake of tryptophan and/or niacin
- precursor supplements are being marketed
- however, while promising, need for more research on efficacy, also concerns about safety
evidence for caloric restriction in improving healthy ageing and longevity in animal studies
- up to 40% increase in longevity in worms
- monkeys in both treatment groups showed decreased chronic disease risk
- one study showed increased lifespan for monkeys, other did not
evidence for caloric restriction in improving healthy ageing and longevity in human studies
-CALERIE trial
- Okinawan pop
- Biosphere-II & CRONies
- CALERIE trial: treatment group couldnt maintain 25% CR (12% over 2 years), they lost 10% bodyweight, BP, blood lipids & inflamm markers were reduced, quality of life indicators improved, longevity & ageing couldnt be assessed
- Okinawan pop had greatest percentage of centenarians in the world
- Biosphere-II & CRONies - too short & other factors involved for it to prove longevity
Concerns about CR in humans
Physical - hypotension, loss of libido, menstrual irregularities,
infertility, bone thinning and osteoporosis, cold sensitivity, loss of strength and
stamina, slower wound healing, and psychological conditions such as
depression, emotional deadening, and irritability
Psychological - dramatic increase in the preoccupation with food,
constant hunger, binge eating, emotional deadening and/or depression, mood
swings, irritability, anxiety, and social isolation
Mediterranean diet & aging
- improve antioxidant capacity and reduce oxidative stress
- reduce circulating inflammatory markers
- improve blood lipid profile
- improved cognitive performance & lower rates of dementia
- higher telomerase activity and telomere maintenance
regions in blue zones
- Loma Linda (USA)
- Nicoya (Costa Rica)
- Sardinia (Italy)
- Ikaria (Greece)
- Okinawa (Japan)
