Background : Segmental progeroid syndromes SPS are rare hereditary diseases in which the affected individuals show signs of premature aging in more than one organ or type of tissue. We review the clinical and genetic features of some of these syndromes and discuss the extent to which their study affords a complementary opportunity to study aging processes in general. Methods: This review is based on publications retrieved by a selective search in PubMed. Results: Segmental progeroid syndromes are a clinically and genetically heterogeneous group of hereditary diseases. They can be categorized, for example, by the age of onset of manifestations congenital vs.
Get smart. Vision dims. Some additional congenital and infantile SPS are listed in the Box. She thought Brooke sounded a lot like Gabby, so contacted Walker. The accumulation of Cream deep penetration pie damaged cells due to telomere shortening over many years may be indicative of why Werner syndrome symptoms only appear after an individual is about twenty years old. She spends her days surrounded by her large family. After prelamin A has been localized to the cell nuclear synvrome, the C-terminal amino acids, including the farnesylated cysteine, are cleaved off Adult aging premature syndrome a specific protease.
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Andrews' Diseases of the Skin: Clinical Dermatology 10th ed. They may decrease the stability of the transcribed messenger RNA mRNAwhich increases the rate at which they are degraded. Here's five changes you may see or feel just by taking more…. It is often treated by Asult the associated diseases and relieving symptoms to improve quality of life. Research suggests that this shortened protein is not transported to the Young girls sucking small dick nucleuswhere it normally interacts with DNA. Coexisting medical conditions. This activation Adult aging premature syndrome p38 may play a role in the onset of premature cell aging, skin aging, cataracts, and graying of the hair. Progeria, also known as "Benjamin Button Disease", children with progeria usually develop the first symptoms during their first few months of life. Categories : Genodermatoses Progeroid syndromes Rare prematuer Senescence. Jun CP can affect syndome entire body, but Adult aging premature syndrome may also only impact one side of it.
Richard Walker has been trying to conquer ageing since he was a year-old free-loving hippie.
- Progeria is an extremely rare autosomal dominant genetic disorder in which symptoms resembling aspects of aging are manifested at a very early age.
- Cerebral palsy CP is a group of nervous system disorders that cause muscle coordination problems and other movement issues.
- Werner syndrome is characterized by the dramatic, rapid appearance of features associated with normal aging.
- Adult premature aging syndrome medical condition : A form of premature aging where sufferers start aging during
- Werner syndrome WS , also known as "adult progeria ",  is a rare, autosomal recessive disorder  which is characterized by the appearance of premature aging.
- The topic Adult Premature Aging Syndrome you are seeking is a synonym, or alternative name, or is closely related to the medical condition Werner Syndrome WS.
Background : Segmental progeroid syndromes SPS are rare hereditary diseases in which the affected individuals show signs of premature aging in more than one organ or type of tissue. We review the clinical and genetic features of some of these syndromes and discuss the extent to which their study affords a complementary opportunity to study aging processes in general. Methods: This review is based on publications retrieved by a selective search in PubMed.
Results: Segmental progeroid syndromes are a clinically and genetically heterogeneous group of hereditary diseases. They can be categorized, for example, by the age of onset of manifestations congenital vs. They are diagnosed on clinical grounds supplemented by genetic testing on the basis of next-generation sequencing, which is of central importance in view of the marked heterogeneity and complexity of their overlapping clinical features.
The elucidation of the genetic and molecular causes of these diseases can lead to causally directed treatment, as shown by the initial clinical trials in Hutchinson— Gilford progeria syndrome. Thus, studying the molecular mechanisms of SPS may be helpful for the development of molecularly defined treatment approaches for age-associated diseases in general. Conclusion: Segmental progeroid syndromes are a complex group of diseases with overlapping clinical features.
Current research efforts focus on the elucidation of the molecular mechanisms of these diseases, most of which are very rare. This should enable the development of treatments that might be applicable to general processes of aging as well. Cellular and organismic aging is a complex biological process, affecting every human being.
Due to the rise in life expectancy, age-related diseases are a challenge of ever increasing proportions for both society and healthcare systems. A targeted, molecularly defined drug intervention for the prevention or treatment of age-associated diseases is indeed an attractive perspective, but unachievable at present due to our incomplete understanding of the molecular mechanisms underlying the regulation of aging processes.
One possible approach to shed light on the molecular basis of aging processes is to study monogenic premature aging syndromes. Segmental progeroid syndromes SPS is the term used for a group of disorders characterized by signs of premature aging in more than one organ or tissue 1.
By contrast, a disorder is classified as unimodal progeroid, if premature aging is limited to one organ or one tissue, e. Among the typical signs of premature aging in SPS is the premature onset of the following symptoms or disorders:.
These signs typically occur in the general population only at a more advanced age. An additional characteristic feature of SPS is growth retardation, because many of the genes involved in the pathogenesis of these syndromes play a role in various aspects of cell viability; consequently, these patients stop growing as the result of significant functional impairment of these genes. More than syndromes with clinical signs of premature aging have so far been described in the scientific literature, but only in recent years have the genetic defects causing these syndromes been identified by analyses performed on at times very few patients, using high-throughput sequencing next-generation sequencing, NGS 2 — 5.
Segmental progeroid syndromes are both clinically and genetically a very heterogeneous group of diseases. Given the significant advances that have been made in recent years in identifying the causes of SPS and a first success in the development of a causative treatment, this review is intended to provide an overview of this rapidly evolving field.
Based on a selective search of the PubMed database, examples of SPS typical for each age of onset will be described and special clinical and genetic features of these syndromes will be highlighted in order to enable the reader to identify these variable and pleiotropic diseases as early as possible. Building on this information, it will be shown, using the Hutchinson—Gilford progeria syndrome as an example, how discovering the genetic cause of a rare syndrome paved the way for the first successful use of a targeted and causative treatment.
Finally, it will be discussed how identifying the underlying genetic and molecular mechanisms as well as developing targeted treatment strategies for rare diseases can also help to improve the management of age-related diseases in general. Since then, about 50 patients with WRS-similar phenotype have been described 6. These patients showed prenatal growth retardation, resulting in reduced weight and length at birth. Typical clinical features include sparse hair, prominent scalp veins, triangular shape of face, sunken eyes, microstomia with maxillary hypoplasia, natal teeth, and a prominent chin Table.
Perinatal respiratory problems are common among these patients. In the further course of the disease, WRS is characterized by growth delays, thin and atrophic skin, generalized lipodystrophy with local fat pads, joint contractures, progressive ataxia and tremor, as well as a global developmental delay 6.
Clinical signs of premature aging include thin and atrophic skin, progressive ataxia and tremor, as well as lipodystrophy with associated cachectic appearance. WRS-causing mutations are often located in introns, i. The life expectancy in patients with WRS is not yet known, but is likely to be strongly associated with the severity of perinatal respiratory problems. Cutis laxa syndromes are a heterogeneous group of rare incidence In addition, many patients present with poor sucking ability, sparse hair, thin and transparent skin with prominent veins, mandibular hypoplasia, and lipodystrophy Table.
Later, these patients may develop a global developmental delay in some cases with cerebral malformations with mild to moderate intellectual disability, microcephaly, and muscular hypotonia. Other clinical signs that typically manifest in the first two years after birth include osteopenia or osteoporosis, finger contractures, cataract, corneal opacity, and movement disorders. Significant progression of these signs is rare in children older than 2 years of age.
The life expectancy of patients with this syndrome also remains unknown to date. While affected children have a normal appearance at birth, they typically develop failure to thrive in their first year of life. In addition, patients experience progressive alopecia, loss of eyebrows and eyelashes, postnatal growth retardation, scleroderma-like skin changes, lipodystrophy, progressive joint contractures, and nail dystrophy Table.
Motor and intellectual development is usually normal. Patients typical die of complications of atherosclerosis after myocardial infarction or stroke; the average life expectancy is approximately 15 years The genetic cause is a recurrent, synonymous, heterozygous de novo mutation c. Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome.
Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome MDPL is a rare incidence Similar to HGPS, affected children appear normal at birth. The first clinical signs rarely manifest before the fifth year of life; then, patients develop unusually thin arms and legs with broad trunk and mandibular hypoplasia. Starting at the age of 10 years, progressive lipodystrophy, dental crowding with irregular positioning of teeth, joint contractures, general muscle wasting, hearing loss, and a high-pitched voice are observed Table.
Later, patients frequently develop type 2 diabetes, telangiectasia, and osteopenia or osteoporosis. The oldest described patient was 62 years old at the time of the last follow-up examination The genetic cause of MDPL are heterozygous mutations in the POLD1 gene which encodes the catalytic subunit of DNA polymerase delta; the majority of patients carry a recurrent deletion of a single amino acid p.
Serdel 14 , Interestingly, other heterozygous POLD1 germline mutations are associated with an increased risk of early-onset colorectal cancer and endometrial cancer polymerase proofreading—associated polyposis, PPAP 16 , which can be regarded as a unimodal progeroid syndrome.
However, patients with MDPL appear not to have a significantly increased tumor risk; thus, a good genotype—phenotype correlation can be assumed for this gene Some additional congenital and infantile SPS are listed in the Box.
WS manifests during adolescence; a characteristic feature is the absence of the growth spurt seen early in puberty. In the further course of the disease, patients often develop bilateral cataract, type 2 diabetes, skin ulcers typically around the ankle , osteoporosis especially of the long bones , calcification in the Achilles tendon, hypogonadism, atherosclerosis of the coronary arteries with increased risk of myocardial infarction, as well as cancers, such as soft-tissue sarcoma, osteosarcoma, melanoma, and thyroid cancer, which are rather rare in the general population Table.
The most common causes of death are cardiovascular disease and cancer; the average life expectancy is 54 years 17 , Myotonic dystrophy type 1 DM1 is a progressive multisystem disorder, primarily characterized by muscular dystrophy.
Although there is a very rare congenital form—characterized by muscular hypotonia and very poor sucking ability, global developmental delay frequently associated with respiratory insufficiency , and early death—, classical DM1 typically manifests no earlier than about age 20 years. As an early clinical sign, an initially distal weakness of the muscles is noted.
Typically, patients present with myotonia, but may in addition develop primarily frontal alopecia, cataract, sensorineural hearing loss, dysarthria and dysphagia, cardiac arrhythmia, hypogonadism, Type 2 diabetes, and hypothyroidism Table. Genetically, the disease is caused by autosomal dominant inherited expansions of unstable CTG repeats in the DMPK gene, which encodes a kinase. The average life expectancy is 48 to 55 years Clinical trials on rare diseases are difficult to conduct as there are few patients available to participate.
The progressive course of the disease can be a further challenge, because conducting a placebo-controlled and randomized, double-blind study can be difficult for ethical reasons.
Understanding the molecular basis of SPS is essential for developing a personalized treatment. Studies on Hutchinson—Gilford progeria syndrome led to the identification of progerin as a likely cause.
This assumption was also supported by the identification of individuals with milder clinical courses who produced less progerin compared to patients with typical HGPS Lamin A is modified by farnesylation and other reactions Figure Therefore, it was assumed that farnesyltransferase inhibitors FTI , originally developed as anti-cancer agents, should, in principle, have a therapeutic potential which was then substantiated in subsequent studies using HGPS cell and mouse models The first clinical study evaluating the FTI lonafarnib in 25 HGPS patients showed after a treatment period of 2 years a reduction in joint stiffness, moderate weight gain, an improvement in bone structure 22 , and a survival benefit of 1.
Side effects included mild diarrhea, fatigue, nausea, vomiting, anorexia, transient elevation of liver enzymes, and transient reduction in serum hemoglobin levels 22 , Likewise, the only recently published data from a lonafarnib-based clinical study with 63 patients demonstrated a reduction in mortality after a median treatment period of 2. These studies show that a drug originally developed for another indication can potentially be used for the treatment of a distinct rare disease. The significance of these findings for our understanding of aging processes.
These findings showed in particular the significance of telomere dysfunction, genomic instability, mitochondrial dysfunction, exhaustion of the stem cell pool, cellular senescence, deregulation of the cell cycle, as well as epigenetic changes and inflammatory processes For example, the normal aging process is also associated with progerin accumulation 27 , HGPS-like defects of the nuclear membrane, changes to histone modifications, increased genomic instability 28 , and reduced expression of specific marker proteins, such as PRKDC, Ku70 and Ku80 The increased epigenetic age in fibroblasts of patients with Werner syndrome is yet another example However, it is important to emphasize that SPS do not represent simple phenocopies of normal aging; for example, osteoporosis in patients with Werner syndrome affects primarily the long bones, while osteoporosis in the general population primarily affects the spine In addition, there are other characteristic signs of SPS, such as mandibular hypoplasia or growth retardation, which are not typical for normal aging.
A recently published pilot study showed mobility improvements in participants after treatment with a senolytic; however, due to the small sample size the results should be interpreted with caution and further randomized studies are needed The various syndromes often show overlapping signs and symptoms, and in many cases significant experience is required for the clinical classification of the different syndromes.
Given the marked heterogeneity, variability and complexity of the overlapping conditions 2 , 3 , 14 , 34 , an NGS-based analysis— described in greater detail by us elsewhere 35 —should be performed as the first diagnostic step in a specialized center.
Early diagnosis prevents a long diagnostic journey, results in a differentiated evaluation of the risk of recurrence for parents and other relatives, and enables the creation of a personalized screening program for an increasing number of affected persons, currently especially patients with Hutchinson—Gilford progeria syndrome and Werner syndrome. In addition, a genetic diagnosis is the foundation for a hopefully increasing number of clinical trials and treatment approaches.
In the long term, exploring and discovering the basis of these rare diseases will also help to obtain a better understanding of normal aging and age-related diseases, potentially paving the way for a targeted positive influence on aging. Conflict of interest statement The authors declare that no conflict of interest exists. Manuscript received on 19 November ; revised version accepted on 13 May Corresponding author Dr.
Dtsch Arztebl Int ; — DOI: Enlarge All figures. Martin GM: Genetic modulation of senescent phenotypes in homo sapiens. Seattle, University of Washington — A prototypical form of segmental progeria. Bird TD: Myotonic dystrophy type 1.
Journal of the American Medical Association. Eriksson; et al. Dermatology: 2-Volume Set. WRN SNPs correlate with cancers such as sarcomas and non-Hodgkin lymphomas, as well as diabetes and cardiovascular problems including atherosclerosis. Hutchinson—Gilford progeria syndrome Restrictive dermopathy. People with CP use three to five times the energy of people without the disorder to complete everyday tasks. Cell Sci.
Adult aging premature syndrome. Adult premature aging syndrome: Related Topics
Also, the altered protein may allow DNA damage to accumulate, which could impair normal cell activities and cause the health problems associated with this condition. Werner syndrome is inherited in an autosomal recessive pattern , which means both copies of the WRN gene in each cell have mutations.
The parents of an individual with Werner syndrome each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. The spectrum of WRN mutations in Werner syndrome patients. Hum Mutat. Werner and Hutchinson-Gilford progeria syndromes: mechanistic basis of human progeroid diseases. Nat Rev Mol Cell Biol. Pathways and functions of the Werner syndrome protein. Mech Ageing Dev. Werner syndrome protein--unwinding function to explain disease.
Sci Aging Knowledge Environ. Role for the Werner syndrome protein in the promotion of tumor cell growth. Epub May Werner syndrome and the function of the Werner protein; what they can teach us about the molecular aging process.
Werner Syndrome. Puzianowska-Kuznicka M, Kuznicki J. Genetic alterations in accelerated ageing syndromes. Do they play a role in natural ageing? Int J Biochem Cell Biol. He noticed these symptoms particularly in a family with four sequential children who all showed the characteristics of the syndrome at around the same age.
He assumed the cause to be genetic, though most of his evidence was clinical. Between and , two internists from New York, Oppenheimer and Kugel, coined the term "Werner Syndrome," igniting a wave of interest and research on the disease. However, it was not until that there was a general consensus on the autosomal recessive mode of inheritance for the syndrome. By , geneticists had located the WRN gene on chromosome 8, leading to its cloning in Since the discovery of the gene, it has become clear that the premature aging displayed in Werner syndrome is not the same, on a cellular level, as normal aging.
The role of WRN in DNA repair and its exonuclease and helicase activities have been the subject of many studies in recent years. Since the initial discovery in , several other cases of Werner syndrome have been recorded.
Many of these cases have occurred in Japan, where a founder effect has caused a higher incidence rate than in other populations. The incidence rate of Werner syndrome in Japan is approximately 1 case per thousand people , , a large contrast with the rate of incidence for the rest of the world, which is between ,, and ,, A founder effect is also apparent in Sardinia, where there have been 18 recorded cases of Werner syndrome.
On the episode "Stargazer in a Puddle" from the television series Bones , the victim has Werner syndrome, the team discovering in the course of the investigation that her mother killed her daughter because she was dying of another disease and worried that her daughter would have nobody to look after her afterwards, with the tragic twist that the mother began to recover from her disease after her daughter's death. Werner syndrome is featured in the film The Fly II , starring Eric Stoltz , were his character was born as a 2 year old baby.
He never sleeps and grows 5 times his normal age due to his biological father having half fly genes from the first film The Fly. Werner syndrome is featured in the film Jack , starring Robin Williams , in which his character ages four times faster than normal. In an early cutscene from the game Metal Gear Solid 4 , Otacon cites "classic Werner syndrome" as the most likely cause of Solid Snake 's premature aging, though he goes on to say that testing had been inconclusive.
It is however later said that Solid Snake's body, created as a genetically engineered clone, had been designed to break down quickly. In The Invisible Man season 1 episode 6, "Impetus", the new character Gloria has an experimentally altered type of Werner syndrome that causes it to become contagious.
In season 1 episode 8 Cold Comfort from TV series Dark Angel , a character has a "form of progeria, similar to Werner syndrome", due to genetic manipulation. With an appropriate treatment, her condition seems to be stabilized. Ratsasan Tamil movie, features a young man born with Werner's and is a victim of childhood bullying due to his appearance and has bad experience proposing to a girl, who turns into serial killer and hunts down and kills school girls.
This article incorporates public domain text from The U. National Library of Medicine. From Wikipedia, the free encyclopedia. Redirected from Adult premature aging syndrome. Werner syndrome progeria Werner syndrome has an autosomal recessive pattern of inheritance. This section is empty. You can help by adding to it. August Andrews' Diseases of the Skin: Clinical Dermatology.
Journal of Human Genetics. On cataract in conjunction with scleroderma. Advances in Experimental Medicine and Biology. Genetics Home Reference. Retrieved 18 March Eur J Dermatol. Medicine Baltimore. Werner Syndrome. Cancer Epidemiol. Biomarkers Prev. Bibcode : PNAS.. Cell Cycle. US National Library of Medicine. Clinical Interventions in Aging. Cancer Biol. Aging Cell. DNA Repair Amst. Bibcode : Natur.
Cancer Inst. Sci Rep. Cell Sci. Nucleic Acids Res. Genes Dev. Effects of donor's age, tissue, and genotype". Cell Genet. Bibcode : PNAS B Biol.
Progeria Information Database. Retrieved April 12, Rejuvenation Res. Clin Interv Aging. ICD - 10 : E Hereditary nonpolyposis colorectal cancer Muir—Torre syndrome Mismatch repair cancer syndrome. Ataxia telangiectasia Nijmegen breakage syndrome.
Progeroid syndromes. Werner syndrome Bloom syndrome Rothmund—Thomson syndrome. Cockayne syndrome Xeroderma pigmentosum Trichothiodystrophy. Hutchinson—Gilford progeria syndrome Restrictive dermopathy. See also: DNA replication and repair-deficiency disorder. Categories : Genodermatoses Autosomal recessive disorders Rare diseases Syndromes affecting the cardiovascular system DNA replication and repair-deficiency disorders Progeroid syndromes Syndromes affecting stature Syndromes affecting bones Syndromes affecting the nervous system.
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Richard Walker has been trying to conquer ageing since he was a year-old free-loving hippie. It was the s, an era marked by youth: Vietnam War protests, psychedelic drugs, sexual revolutions. The young Walker relished the culture of exultation, of joie de vivre, and yet was also acutely aware of its passing. He was haunted by the knowledge that ageing would eventually steal away his vitality — that with each passing day his body was slightly less robust, slightly more decayed.
One evening he went for a drive in his convertible and vowed that by his 40th birthday, he would find a cure for ageing. Walker became a scientist to understand why he was mortal. Scientists have published several hundred theories of ageing, and have tied it to a wide variety of biological processes. But no one yet understands how to integrate all of this disparate information. He has identified four girls with this condition, marked by what seems to be a permanent state of infancy, a dramatic developmental arrest.
His quest for immortality depends on finding it. She drives an enormous SUV, but her six children and their coats and bags and snacks manage to fill every inch. The three big kids are bouncing in the very back. Sophia, 10, with a mouth of new braces, is complaining about a boy-crazy friend. The three little kids squirm in three car seats across the middle row. Myah, two, is mining a cherry slushy, and Luke, one, is pawing a bag of fresh crickets bought for the family gecko.
She has long, skinny legs and a long, skinny ponytail, both of which spill out over the edges of her car seat. But she has the buttery skin, tightly clenched fingers and hazy awareness of a newborn.
Back in , when MaryMargret and her husband, John, went to the hospital to deliver Gabby, they had no idea anything was wrong. They knew from an ultrasound that she would have clubbed feet, but so had their other daughter, Sophia, who was otherwise healthy. And because MaryMargret was a week early, they knew Gabby would be small, but not abnormally so. Gabby came out purple and limp.
Doctors stabilised her in the neonatal intensive care unit and then began a battery of tests. Within days the Williamses knew their new baby had lost the genetic lottery. Her optic nerve, which runs between the eyes and the brain, was atrophied, which would probably leave her blind.
She had two heart defects. She had a cleft palate and an abnormal swallowing reflex, which meant she had to be fed through a tube in her nose. Their family priest came by to baptise her. Unlike typical babies, Gabby Williams was born with a smooth frontal lobe in her brain, along with a number of other developmental defects SPL. Day after day, MaryMargret and John shuttled between Gabby in the hospital and month-old Sophia at home. The doctors tested for a few known genetic syndromes, but they all came back negative.
Nobody had a clue what was in store for her. Her strong Catholic family put their faith in God. And after 40 days, she did. Gabby cried a lot, loved to be held, and ate every three hours, just like any other newborn.
At four months old she started having seizures. John and MaryMargret took her to specialist after specialist: a cardiologist, a gastroenterologist, a geneticist, a neurologist, an ophthalmologist and an orthopaedist. But the experts always said the same thing: nothing could be done. The first few years with Gabby were stressful. For nearly all of those miles, Gabby cried and screamed. This continued for months until doctors realised she had a run-of-the-mill bladder infection. Around the same period, she acquired a severe respiratory infection that left her struggling to breathe.
But the tiny toddler toughed it out. She was developing in subtle ways, but at her own pace. She looked down at Gabby and was shocked to see her eyes reacting to the sunlight. Despite the hardships, the couple decided they wanted more children. In MaryMargret had Anthony, and the following year she had Aleena. By this time, the Williamses had stopped trudging to specialists, accepting that Gabby was never going to be fixed. His studies investigated how food, light, hormones and brain chemicals influence fertility in rats.
But academic science is slow. He was running out of time. So he went back to the drawing board. As he describes in his book, Why We Age, Walker began a series of thought experiments to reflect on what was known and not known about ageing.
Ageing is usually defined as the slow accumulation of damage in our cells, organs and tissues, ultimately causing the physical transformations that we all recognise in elderly people. Jaws shrink and gums recede. Skin slacks. Bones brittle, cartilage thins and joints swell.
Arteries stiffen and clog. Hair greys. Vision dims. Memory fades. The notion that ageing is a natural, inevitable part of life is so fixed in our culture that we rarely question it. But biologists have been questioning it for a long time. Our young cells survive only because they have a slew of trusty mechanics on call. Take DNA, which provides the all-important instructions for making proteins. Every time a cell divides, it makes a near-perfect copy of its three-billion-letter code.
Copying mistakes happen frequently along the way, but we have specialised repair enzymes to fix them, like an automatic spellcheck. Proteins, too, are ever vulnerable. If it gets too hot, they twist into deviant shapes that keep them from working. Happily, our tissues are stocked with antioxidants and vitamins that neutralise this chemical damage. Time and time again, our cellular mechanics come to the rescue. One theory is that it all boils down to the pressures of evolution.
Humans reproduce early in life, well before ageing rears its ugly head. All of the repair mechanisms that are important in youth — the DNA editors, the heat shock proteins, the antioxidants — help the young survive until reproduction, and are therefore passed down to future generations. Hence, ageing. Most scientists say that ageing is not caused by any one culprit but by the breakdown of many systems at once. Our sturdy DNA mechanics become less effective with age, meaning that our genetic code sees a gradual increase in mutations.
Telomeres, the sequences of DNA that act as protective caps on the ends of our chromosomes, get shorter every year. Epigenetic messages, which help turn genes on and off, get corrupted with time. Heat shock proteins run down, leading to tangled protein clumps that muck up the smooth workings of a cell. Faced with all of this damage, our cells try to adjust by changing the way they metabolise nutrients and store energy.
To ward off cancer, they even know how to shut themselves down. But eventually cells stop dividing and stop communicating with each other, triggering the decline we see from the outside. The telomeres that protect our chromosomes get progressively shorter as we age SPL. Scientists trying to slow the ageing process tend to focus on one of these interconnected pathways at a time. Some researchers have shown, for example, that mice on restricted-calorie diets live longer than normal.
Other labs have reported that giving mice rapamycin, a drug that targets an important cell-growth pathway, boosts their lifespan. Still other groups are investigating substances that restore telomeres, DNA repair enzymes and heat shock proteins. During his thought experiments, Walker wondered whether all of these scientists were fixating on the wrong thing.
What if all of these various types of cellular damages were the consequences of ageing, but not the root cause of it? He came up with an alternative theory: that ageing is the unavoidable fallout of our development. He was working in his home office when his wife called out to him to join her in the family room. Brooke Greenberg was 12 years old, but just 13 pounds 6kg and 27 inches 69cm long. Her doctors had never seen anything like her condition, and suspected the cause was a random genetic mutation.
Walker was immediately intrigued. He had heard of other genetic diseases, such as progeria and Werner syndrome, which cause premature ageing in children and adults respectively. But this girl seemed to be different. She had a genetic disease that stopped her development and with it, Walker suspected, the ageing process. Brooke Greenberg, in other words, could help him test his theory.
Brooke was born a few weeks premature, with many birth defects.