Borrowed Time: The Science of How and Why We Age

by Sue Armstrong

A growing number of respected scientists even believe that ageing is a disease, and it can be treated. Some go so far as to suggest ageing can be ‘cured’, so that we too could potentially live forever.

A five-year-old girl in the UK today can expect to live to a little over 80 years. But evidence suggests that her last 19 or 20 years will likely be dogged by ill health.

‘Over the past 50 years, health care hasn't slowed the ageing process so much as it has slowed the dying process.’

Evolutionary ideas dominated the field in its early days, and continue to provide the framework for much of what goes on in geroscience today.

The disposable soma theory suggests that the degree of investment in maintaining the body of any creature, and thus its lifespan, is determined by its environment.

The nine characteristics

• Instability of the genome.

• Telomere attrition.

• Epigenetic alterations.

• Loss of proteostasis.

• Deregulation of nutrient sensing.

• Mitochondrial dysfunction.

• Cellular senescence.

• Stem-cell exhaustion.

• Altered communication between the cells of the body.

He supported his hypothesis by demonstrating that he could increase the lifespan of laboratory mice by up to 30 per cent by giving them drugs to protect them

against radiation.

The relative weakness of antioxidant therapy perplexed Harman for a long time and led him eventually to conclude that most free radicals are generated inside the mitochondria,

many studies were reported that didn't support that theory. Including

human studies…

In some cases taking antioxidants actually increased mortality rates slightly.’

Fifteen years ago you'd go to ageing meetings and you'd have talk after talk referring everything to oxidative damage. Now you can go to conferences and you hear almost nothing about it.’

Hayflick became aware that, at some point, the cells would stop dividing and that this seemed to be a predictable event that occurred after about 50 population doublings. He was particularly intrigued by the fact that the cells didn't die; they continued to metabolise and could live in that non-dividing state for a year or more.

Cancer and ageing, she observed, seem to be two sides of the same coin: ageing is the price we pay for protection against cancer, in that Nature's way of limiting the proliferation of potentially dangerous cells is to put a brake on their ability to divide after a certain length of time.

Stem cells occupy little pockets, or ‘niches’, in the various tissues where they wait to be called on for repair purposes.

But one of the most important ways in which senescent cells are thought to promote ageing is through chronic inflammation

senescent cells were clustered at the site of the wounds. When they eliminated the senescent cells, the wounds were very much slower to heal.

‘It's this double-edged sword again,’ comments Campisi. Senescent cells, it seems, are needed to promote tissue repair and for healthy development. ‘But you don't want them sticking around.’

There are two schools of thought about how to prevent the damage done by senescent cells. One strategy is to develop agents known as senolytics that will kill the cells, sending them off for recycling. The other is to rejuvenate the cells so that they function normally again.

One good reason why skin cells are primed to senesce rather than to commit suicide when the damage signal goes off is that we cannot afford to lose too many of the cells that hold us together.

‘If you turn on telomerase in middle-aged mice, they do rejuvenate. The muscle mass increases; the gut shows improvement; I think even their brain size increased [in the experiments]. But if the mice had a precancerous tumour, it became very aggressive very quickly.’

If TOR is working too long or too hard it will drive a cell to senesce.

if you inhibit TOR, you slow down protein production, and you turn on the housekeeping programme that recycles all the worn-out components; senescent cells become younger again,

The drawback with rapamycin, however, is that it can have a range of more or less uncomfortable and serious side effects, ranging from constipation and swollen ankles to abnormally high levels of cholesterol and sugar in the blood, and increased risk of type 2 diabetes.

60 per cent of the fly's genes occur in us,

We now know that around 75 per cent of genes known to be involved in human diseases are also found in Drosophila.

More than one-third of C. elegans genes have counterparts in humans.

What stands out most clearly as special in the molluscs – and indeed in several other long-lived species that have been studied – is the extraordinary stability of their proteins,

over time, your proteins in some cells – particularly in your cells that last a long time – gradually get misfolded and degraded and that can cause them to become toxic as well

as dysfunctional.’

researchers bathed some beta-amyloid in clam ‘juice’ – the extracted contents of muscle cells – and found that the amyloid was unable to clump together.

It turns out that elephants have 20 copies of p53,

Longevity in Johnson and Friedman's worms, however, came at the price of poor sexual function and impaired fertility.

‘daf-2 mutants were the most amazing things I had ever seen,’ writes Kenyon in her review. ‘They were active and healthy and they lived more than twice as long as normal.

So how does the gene work? It turns out it's part of what's called a ‘nutrient-sensing’ network,

The daf-2 gene is the recipe for a structure on the surface of cells (a so-called receptor molecule) that is the entry point into the cell of important hormones – insulin and growth factors.

Mutant daf-2 builds faulty receptors that limit the amount of hormone getting into the cell.

The alarm signal activates a caretaker gene called FOXO,

The tasks of these genes are, variously, to protect the cells from oxidative stress (free radicals); to repair or recycle damaged components; and to make sure that other proteins in the cell are formed and functioning properly.

‘The idea is that you find the genes that control ageing and then you discover what ageing is. But it's turned out to be very difficult,’