Science: Why the clock of ages keeps some ticking past 100

Everybody ages - but nobody knows why, though a huge scientific effort has gone into this eternal question. Is ageing in the genes or the environment? Data from mothers who gave birth after 40 and lived to 100 could answer the question, reports Charles Arthur
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The Independent Culture
Thomas Perls knows what he's looking for: a city. It doesn't exist on any map, though its inhabitants are easily recognised - they are all siblings who have lived to ages of 90 or more.

It's a city built on genes accumulated over thousands of generations, a city built on blood. For somewhere in the DNA of those siblings is a huge community, probably thousands, of genes which (barring accidents) ensure their owner a long and healthy life. And, bizarrely, some of those genes may have come from bacteria.

Dr Perls is based at the gerontology division at the Beth Israel-Deaconess Medical Center attached to Harvard Medical School in Boston, Massachusetts. Last week, his latest research was published in Nature, a careful study showing that women born in 1896 who had lived to be 100 were four times more likely to have had a child when in their forties than another group of women who died aged 73.

At first, it looks like a spurious result. Why should the age when you have a child, and your lifespan, be connected? Conversely, once you decide that this reveals some underlying fact, it's easy to exaggerate its message - to conclude that going through pregnancy and childbirth at an advanced age somehow ensures longer life. That's not so. Scientists are sure that the eventual length of our individual lives is heavily dependent on the genes we are born with, not on how many times (or when) you give birth.

But having a child in your forties means you have not reached the menopause, when the ovaries stop producing eggs and stop making the female hormone oestrogen (which has been shown to protect against age-related problems such as Alzheimer's disease, heart disease and strokes). In fact, it may be that these women are ageing more slowly than those who died earlier. We'll return to the menopause in a moment. But it's worth noting first that nobody actually knows what ageing is. That doesn't mean there's any shortage of suggestions; currently three main theories are battling it out. The first is that we age because our chromosomes have a "fuse", the telomere. With every cell division, the telomere shortens, and when it reaches a certain length the cell refuses to divide again, and quietly dies. So does ageing equate to telomere shortening? But some cells - such as sperm and ova, and also cancer cells - can rebuild their telomeres. Logically, organisms that don't shorten their telomeres would have an evolutionary advantage; that may suggest that it's just a protection mechanism against cancer.

The second theory pins the blame for ageing on the build-up over the years of genetic damage to the DNA in the nucleus, caused either by environmental toxins (such as free radicals) or by radiation. Damaged cells which cannot repair their DNA also die quietly, suggests the theory; when too many cells have died, the organism dies.

The third theory focuses on the mitochondria, the powerhouses of the cell. They lie outside the nucleus, and have their own DNA. Biologists are almost certain that billions of years ago they were free-floating bacteria, which were then absorbed by the cells which in time evolved into eukaryotic cells (such as plants and animals). Significantly, because they lie outside the nucleus, the mitochondrial DNA are passed down through the maternal line: you never inherit your father's mitochondria. Perls's study, you'll note, looks at mothers. According to this theory, the mitochondria determine the lifespan of the cell; their genes and mechanisms become increasingly damaged. As this damage accumulates, their efficiency drops until the cell dies because its energy source has run down like a clock spring.

Which theory is right? It's still unclear. But the new work by Dr Perls suggests that somehow the women who gave birth later were ageing more slowly than those in the group who died aged 73. "Ideally, we would have liked to measure when the women in the two groups went through menopause," says Dr Perls. "But even just asking the centenarians is a pretty difficult chore." As for the women who died in 1969, "finding out when they last had a child is a relative approximation." It does at least put a "later than" date on the event. On that basis, the 100-year-olds appeared to have had a later menopause, which implies that somehow their internal clocks were just running more slowly, with all the benefits - including longer exposure to oestrogen - that that confers. The menopause remains a biological event that baffles evolutionists. According to the "selfish gene" theory, once your body cannot reproduce, nature has no further use for you. So why should the menopause evolve? An infertile member of a species competes for resources with fertile members, which seems daft. Also, evolution should favour the emergence of women who can bear children beyond their menopausal relatives. Why don't they exist? An important clue there is that humans appear to be the only mammals which undergo the menopause.

As part of his follow-up work, Dr Perls is trying to find families with siblings who have lived into their nineties and beyond. "We're aiming to take a blood sample and look for large areas of DNA which are the same in both, with the idea that if they have those areas - well, that's the city. The genes which determine how fast those people age are housed in that city." He, of course, wants to track them down to their houses. It's unlikely to be a single gene; he guesses there may be more than 8,000.

He is not limiting himself to the cell nucleus DNA, though. "I'm very interested in the mitochondrial genes, and how they may modulate the efficiency with which the mitochondria produce energy and ATP [the basic chemical for storing energy in cells]. They may play a big role in how fast we age."