the road to longevity: the molecular basis of lifespan becomes clearer

August 14, 2005

Journal of Hypertension. 23(7):1285-1309, July 2005.

A forkhead in the road to longevity: the molecular basis of lifespan becomes clearer

[Reviews]

, J

Diet and lifestyle

For just about all common diseases, be they cardiovascular, oncological or neurological, the messages on prevention, and thus postponement of death, are remarkably similar – don’t smoke, don’t drink alcohol, get plenty of exercise, meditate, reduce calories as well as sodium chloride, animal fats, trans fatty acids and proteins, consume low glycaemic index foods [16,17], have 6–9 servings of vegetables and fruit per day, including soya products, whole grains and nuts, and consume ‘good oils’ such olive oil and omega-3 fatty acids in cold-water fish [18,19]. In the case of alcohol, although a J-shaped relationship has been found for cardiovascular disease, the benefits apply mostly to middle-aged people with high cholesterol indicative of a poor diet and lifestyle, but for cancer risk there is no threshold below which risk is absent [20].

Caloric restriction

It has been known for 80 years that enormous increases in lifespan can be achieved in laboratory animals by restricting caloric intake by 30–40%, while maintaining adequate nutrient intake [31–34]. In 25% of rats autopsy has, moreover, failed to reveal the cause of death. Limiting growth during just the postnatal period of suckling increases lifespan and protects against an obesity-inducing diet later in life, whereas reduced growth in utero followed by catch-up growth postnatally shortens lifespan, particularly when a cafeteria-style diet is provided from day 21 [35]. In human terms, these data represent the difference between living to age 50 or age 75.

Caloric restriction reduces protein synthesis in liver and skeletal muscle, as well as the load of oxidized proteins [36], owing to faster turnover and thus decreased metabolic toxin exposure [37]. Immune function is enhanced and inflammatory responses of ageing are inhibited [37]. As well, cancer is reduced, accompanied by increased apoptosis (‘programmed cell death’) [37]. Lack of obesity also contributes.

The first human experiment was in the 16th century when Luigi Cornaro, at age 40, deliberately restricted his food intake for health reasons and lived to 102 [40]. More recently human volunteers sealed inside Biosphere 2 for 2 years had to produce their own food, became calorically restricted, and their physiological and biochemical parameters changed to resemble those of food-restricted monkeys and rats [41].

August 14, 2005

Jim,

I looked up the referenced paper and found an entirely different

abstract-- one that made more sense in relation to the title of your

last message than the abstract below it:

Abstract:

Objective: Although the quest for longevity is as old as civilization

itself, only recently have technical and conceptual advances in

genomics research brought us to the point of understanding the precise

molecular events that make us age. This heralds an era when

manipulations of these will enable us to live longer, healthier lives.

The present review describes how recent experimental strategies have

identified key genes and intracellular pathways that are responsible

for ageing and longevity.

Findings: In diverse species transcription factors belonging to the

forkhead/winged helix box gene, group O (FOXO) subfamily have been

found to be crucial in downstream suppression of the life-shortening

effects of insulin/insulin-like growth factor-I receptor signalling

pathways that, when upregulated, accelerate ageing by suppression of

FOXO. The various adverse processes activated upon FOXO suppression

include increased generation of reactive oxygen species (ROS). ROS are

pivotal for the onset of various common conditions, including

hypertension, atherosclerosis, type 2 diabetes, cancer and Alzheimer's

disease, each of which shortens lifespan. In humans, FOXO3a, as well

as FOXO1 and -4, and their downstream effectors, could hold the key to

counteracting ageing and common diseases. An understanding of the

processes controlled by these FOXOs should permit development of novel

classes of agents that will more directly counteract or prevent the

damage associated with diverse life-threatening conditions, and so

foster a life of good health to a ripe old age. Just like caloric

restriction, lifespan can be increased in various species by

plant-derived polyphenols, such as resveratrol, via activation of

sirtuins in cells. Sirtuins, such as SIRT1 in mammals, utilize FOXO

and other pathways to achieve their beneficial effects on health and

lifespan.

Conclusion: Lifespan is tractable and basic mechanisms are now known.

Longevity research complements and overlaps research in most major

medical disciplines. Current progress bodes well for an

ever-increasing length of healthy life for those who adapt emerging

knowledge personally (so-called 'longevitarians').

--- In , " jwwright " <jwwright@e...>

wrote:

> Re: [ ] Dairy, Calcium helps fat lossJournal of

Hypertension. 23(7):1285-1309, July 2005.

> A forkhead in the road to longevity: the molecular basis of lifespan

becomes clearer

> [Reviews]

> , J

>

> Diet and lifestyle

> For just about all common diseases, be they cardiovascular,

oncological or neurological, the messages on prevention, and thus

postponement of death, are remarkably similar - don't smoke, don't

drink alcohol, get plenty of exercise, meditate, reduce calories as

well as sodium chloride, animal fats, trans fatty acids and proteins,

consume low glycaemic index foods [16,17], have 6-9 servings of

vegetables and fruit per day, including soya products, whole grains

and nuts, and consume 'good oils' such olive oil and omega-3 fatty

acids in cold-water fish [18,19]. In the case of alcohol, although a

J-shaped relationship has been found for cardiovascular disease, the

benefits apply mostly to middle-aged people with high cholesterol

indicative of a poor diet and lifestyle, but for cancer risk there is

no threshold below which risk is absent [20].

>

> Caloric restriction

> It has been known for 80 years that enormous increases in lifespan

can be achieved in laboratory animals by restricting caloric intake by

30-40%, while maintaining adequate nutrient intake [31-34]. In 25% of

rats autopsy has, moreover, failed to reveal the cause of death.

Limiting growth during just the postnatal period of suckling increases

lifespan and protects against an obesity-inducing diet later in life,

whereas reduced growth in utero followed by catch-up growth

postnatally shortens lifespan, particularly when a cafeteria-style

diet is provided from day 21 [35]. In human terms, these data

represent the difference between living to age 50 or age 75.

>

> Caloric restriction reduces protein synthesis in liver and skeletal

muscle, as well as the load of oxidized proteins [36], owing to faster

turnover and thus decreased metabolic toxin exposure [37]. Immune

function is enhanced and inflammatory responses of ageing are

inhibited [37]. As well, cancer is reduced, accompanied by increased

apoptosis ('programmed cell death') [37]. Lack of obesity also

contributes.

>

> The first human experiment was in the 16th century when Luigi

Cornaro, at age 40, deliberately restricted his food intake for health

reasons and lived to 102 [40]. More recently human volunteers sealed

inside Biosphere 2 for 2 years had to produce their own food, became

calorically restricted, and their physiological and biochemical

parameters changed to resemble those of food-restricted monkeys and

rats [41].

August 14, 2005