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Passing on the DNA of old age

Passing on the DNA of old age


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I've often pondered the fact that we only pass on the DNA of our youth. Any mutations to our DNA that occur after having children, that may help us to respond to getting older, are not inherited. Do older parents pass on a different, perhaps more learned "quality" of DNA? Anyone know the answer to this?


It is good thinking you're doing here!

Only mutations happening in the germ line can be passed on

Mutations that happen in an individual hand (or any other soma line) will not be passed on the the offspring. Only those happening in the soma line can.

Mutations are random

What I mean here is that it is not because someone is old that all of sudden the mutations that would happen in this person would be beneficial for old people.

Age dependent "quality" of genome being passed on

You are asking

Do older parents pass on a different, perhaps more learned "quality" of DNA?

You seem to misunderstand how natural selection works. An individual alone does not get selected over its lifetime to become better (at least not in the sense of what is meant by "natural selection"). You need a population for selection to happen.

In the females as the pool of ovules is being set early in life. In males the spermatozoids keep replicating during the whole lifetime of the individual. Hence, in males, but not in females, the number of new mutations being passed on to their offspring should increase with age and it does.

In humans the mother transmit on average 15 new mutations and the father transmit on average $25+2(g−20)$ new mutations, where $g$ is the age of the father (Cochrane and Harpending, 2013; this approximation holds only for men older than 20 years of course).

As the vast majority of mutations are neutral or deleterious, the "quality" of the genome being passed on should decrease with age unlike you expected.

Efficiency of selection decreases with age

The fact that after a given age, one does not reproduce anymore (among mammals, this is particularly true for women) does affect the selection pressures on the genetic variants that affect age specific fitness. e.g. A mutation that will reduce health at young age will be quite strongly selected against while a mutation that affect health at old will not.

When talking about this discrepancy between selection pressures at different ages, the concept of antagonist pleiotropy often comes into the discussion. Pleiotropy is the phenomenon where one locus affect several traits.

The idea of age-specific antagonist pleiotropy is that a mutation that will increase health at a young age by a factor $s$ but decrease it at an old age by the same factor $s$ will be selected for. Such process can cause a population to evolve toward lower lifespan. The antagonistic pleiotropy hypothesis is one of the most important hypothesis that we have for the evolution of senescence.

Evolution of senescence

You might want to have a look at the posts:


The Birth and Death of Cells

The growth and replication of cells is often described as a cyclic process with two main phases: interphase , when the cell grows and replicates DNA in preparation for cell division, and mitosis , during which the actual division of the cell into two daughter cells occurs. The events occurring in this cyclic process are summarized in the diagram on the right in which interphase events are shown with blue arrows and mitosis is shown in brown. Note that cells may also exit the cycle and enter a G0 phase either temporarily or more or less permanently. In cells that are actively growing and dividing, such as those in an embryo, the cycle is completed frequently as cells divide over and over as the embryo grows and develops. In adults the need for growth and development has passed, and most cells remain in the G0 phase during which they perform their specialized functions, but they no longer replicate (e.g., nerve and muscle cells). Nevertheless, even in fully developed adults certain progenitor cells retain the ability to replicate and give rise to new daughter cells to replace cells that are damaged or lost due to wear and tear. For example, Clara cells in the epithelium of the respiratory tract have the capacity to replicate to produce two daughter cells - one that will be a new Clara cell and one that will differentiate into a replacement epithelial cell. Similarly, hematopoetic stem cells in bone marrow have the ability to replicate to give rise to progenitor cells that can differentiate into the various cellular elements of blood.

Regulation of the cell cycle is of critical importance to the aging process. Replication should only occur when there is a need for growth and development (in embryos and the young) or when there is a need to replace damaged or lost cells. Thus, the cycle is influenced by growth factors and by proto-oncogenes that favor replication and by anti-oncogenes that produce proteins that inhibit replication. These various factors interact to regulate the cell cycle in cells that have retained the capacity to divide. In addition, there are cellular processes that constitute checkpoints that prevent the cell cycle from proceeding if errors have occurred. The first checkpoint occurs during the G1 phase and provides an opportunity for cellular that processes to repair damaged DNA before the cell enters the S phase when replication occurs. This prevents the daughter cells from inheriting damaged DNA, which would result in mutations. There are also other checkpoints in S and G2 phases that check for damaged DNA and failure of DNA replication. The final cell cycle checkpoint occurs at the end of mitosis and checks for any chromosomes that have been misaligned. The many factors that regulate the cell cycle play an important rol in the aging process, because as cells age their capacity to replicate diminishes to the point that they are no longer able to divide. As this occurs, the ability to replace damaged or lost cells dwindles and ultimately results in declines in tissue strength and cellular and organ function that are characteristic of aging.


Contents

Evidence for a paternal age effect has been proposed for a number of conditions, diseases and other effects. In many of these, the statistical evidence of association is weak, and the association may be related by confounding factors or behavioural differences. [9] [3] Conditions proposed to show correlation with paternal age include the following: [10]

Single-gene disorders Edit

Advanced paternal age may be associated with a higher risk for certain single-gene disorders caused by mutations of the FGFR2, FGFR3 and RET genes. [11] These conditions are Apert syndrome, Crouzon syndrome, Pfeiffer syndrome, achondroplasia, thanatophoric dysplasia, multiple endocrine neoplasia type 2, and multiple endocrine neoplasia type 2b. [11] The most significant effect concerns achondroplasia (a form of dwarfism), which might occur in about 1 in 1,875 children fathered by men over 50, compared to 1 in 15,000 in the general population. [12] However, the risk for achondroplasia is still considered clinically negligible. [13] The FGFR genes may be particularly prone to a paternal age effect due to selfish spermatogonial selection, whereby the influence of spermatogonial mutations in older men is enhanced because cells with certain mutations have a selective advantage over other cells (see § DNA mutations). [14]

Pregnancy effects Edit

Several studies have reported that advanced paternal age is associated with an increased risk of miscarriage. [15] The strength of the association differs between studies. [16] It has been suggested that these miscarriages are caused by chromosome abnormalities in the sperm of aging men. [15] An increased risk for stillbirth has also been suggested for pregnancies fathered by men over 45. [16]

Birth outcomes Edit

A systematic review published in 2010 concluded that the graph of the risk of low birthweight in infants with paternal age is "saucer-shaped" (U-shaped) that is, the highest risks occur at low and at high paternal ages. [17] Compared with a paternal age of 25–28 years as a reference group, the odds ratio for low birthweight was approximately 1.1 at a paternal age of 20 and approximately 1.2 at a paternal age of 50. [17] There was no association of paternal age with preterm births or with small for gestational age births. [17]

Mental illness Edit

Schizophrenia is thought by some to be associated with advanced paternal age but it is not proven. [18] [19] [20] Some studies examining autism spectrum disorder (ASD) and advanced paternal age have demonstrated an association between the two, although there also appears to be an increase with maternal age. [21]

In one study, the risk of bipolar disorder, particularly for early-onset disease, is J-shaped, with the lowest risk for children of 20- to 24-year-old fathers, a twofold risk for younger fathers and a threefold risk for fathers >50 years old. There is no similar relationship with maternal age. [22] A second study also found a risk of schizophrenia in both fathers above age 50 and fathers below age 25. The risk in younger fathers was noted to affect only male children. [23]

A 2010 study found the relationship between parental age and psychotic disorders to be stronger with maternal age than paternal age. [24]

A 2016 review concluded that the mechanism behind the reported associations was still not clear, with evidence both for selection of individuals liable to psychiatric illness into late fatherhood and evidence for causative mutations. The mechanisms under discussion are not mutually exclusive. [25]

A 2017 review concluded that the vast majority of studies supported a relationship between older paternal age and autism and schizophrenia but that there is less convincing and also inconsistent evidence for associations with other psychiatric illnesses. [3]

Cancers Edit

Paternal age may be associated with an increased risk of breast cancer, [26] but the association is weak and there are confounding effects. [10]

According to a 2017 review, there is consistent evidence of an increase in incidence of childhood acute lymphoblastic leukemia with paternal age. Results for associations with other childhood cancers are more mixed (e.g. retinoblastoma) or generally negative. [3]

Diabetes mellitus Edit

High paternal age has been suggested as a risk factor for type 1 diabetes, [27] but research findings are inconsistent, and a clear association has not been established. [28] [29]

Down syndrome Edit

It appears that a paternal-age effect might exist with respect to Down syndrome, but it is very small in comparison to the maternal-age effect. [30] [31]

Intelligence Edit

A review in 2005 found a U-shaped relationship between paternal age and low intelligence quotients (IQs). [32] The highest IQ was found at paternal ages of 25–29 fathers younger than 25 and older than 29 tended to have children with lower IQs. [32] It also found that "at least a half dozen other studies . have demonstrated significant associations between paternal age and human intelligence." [32] A 2009 study examined children at 8 months, 4 years and 7 years and found that higher paternal age was associated with poorer scores in almost all neurocognitive tests used but that higher maternal age was associated with better scores on the same tests [33] this was a reverse effect to that observed in the 2005 review, which found that maternal age began to correlate with lower intelligence at a younger age than paternal age, [32] however two other past studies were in agreement with the 2009 study's results. [24] An editorial accompanying the 2009 paper emphasized the importance of controlling for socioeconomic status in studies of paternal age and intelligence. [34] A 2010 study from Spain also found an association between advanced paternal age and intellectual disability. [24]

On the other hand, later research concluded that previously reported negative associations might be explained by confounding factors, especially parental intelligence and education. A re-analysis of the 2009 study found that the paternal age effect could be explained by adjusting for maternal education and number of siblings. [35] A 2012 Scottish study found no significant association between paternal age and intelligence, after adjusting what was initially an inverse-U association for both parental education and socioeconomic status as well as number of siblings. [36] A 2013 study of half a million Swedish men adjusted for genetic confounding by comparing brothers and found no association between paternal age and offspring IQ. [37] Another study from 2014 found an initially positive association between paternal age and offspring IQ that disappeared when adjusting for parental IQs. [38]

Life expectancy Edit

A 2008 paper found a U-shaped association between paternal age and the overall mortality rate in children (i.e., mortality rate up to age 18). [39] Although the relative mortality rates were higher, the absolute numbers were low, because of the relatively low occurrence of genetic abnormality. The study has been criticized for not adjusting for maternal health, which could have a large effect on child mortality. [40] The researchers also found a correlation between paternal age and offspring death by injury or poisoning, indicating the need to control for social and behavioral confounding factors. [41]

In 2012, a study showed that greater age at paternity tends to increase telomere length in offspring for up to two generations. Since telomere length has effects on health and mortality, this may have effects on health and the rate of aging in these offspring. The authors speculated that this effect may provide a mechanism by which populations have some plasticity in adapting longevity to different social and ecological contexts. [42]

Fertility of the father Edit

A 2001 review suggested older men have decreased pregnancy rates, increased time to pregnancy and increased infertility at a given point in time. [43] When controlling for the age of the female partner, comparisons between men under 30 and men over 50 found relative decreases in pregnancy rates between 23% and 38%. [43]

Father's age versus father's risk of death
(among French population) [44]
Father's age
at birth
Risk of father's death
before child's 18th birthday
20 1.5%
25 2.2%
30 3.3%
35 5.4%
40 8.3%
45 12.1%

Parents do not decide when to reproduce randomly. This implies that paternal age effects may be confounded by social and genetic predictors of reproductive timing.

A simulation study concluded that reported paternal age effects on psychiatric disorders in the epidemiological literature are too large to be explained only by mutations. They conclude that a model in which parents with a genetic liability to psychiatric illness tend to reproduce later better explains the literature. [9]

Later age at parenthood is also associated with a more stable family environment, with older parents being less likely to divorce or change partners. [44] Older parents also tend to occupy a higher socio-economic position and report feeling more devoted to their children and satisfied with their family. [44] On the other hand, the risk of the father dying before the child becomes an adult increases with paternal age. [44]

To adjust for genetic liability, some studies compare full siblings. Additionally, or alternatively, studies statistically adjust for some or all of these confounding factors. Using sibling comparisons or adjusting for more covariates frequently changes the direction or magnitude of paternal age effects. For example, one study drawing on Finnish census data concluded that increases in offspring mortality with paternal age could be explained completely by parental loss. [45] On the other hand, a population-based cohort study drawing on 2.6 million records from Sweden found that risk of attention deficit hyperactivity disorder was only positively associated with paternal age when comparing siblings. [46]

Several hypothesized chains of causality exist whereby increased paternal age may lead to health effects. [16] [47] There are different types of genome mutations, with distinct mutation mechanisms:

  • DNA length mutations of repetitive DNA (such as telomeres and microsatellites), caused by cellular copying errors
  • DNA point mutations, caused by cellular copying errors and also by chemical and physical insults such as radiation
  • chromosome breaks and rearrangements, which can occur in the resting cell
  • epigenetic changes, i.e. methylation of the DNA, which can activate or silence certain genes, and is sometimes passed down from parent to child

Telomere length Edit

Telomeres are repetitive genetic sequences at both ends of each chromosome that protect the structure of the chromosome. [48] As men age, most telomeres shorten, but sperm telomeres increase in length. [16] The offspring of older fathers have longer telomeres in both their sperm and white blood cells. [16] [48] A large study showed a positive paternal, but no independent maternal age effect on telomere length. Because the study used twins, it could not compare siblings who were discordant for paternal age. It found that telomere length was 70% heritable. [49]

DNA point mutations Edit

In contrast to oogenesis, the production of sperm cells is a lifelong process. [16] Each year after puberty, spermatogonia (precursors of the spermatozoa) divide meiotically about 23 times. [47] By the age of 40, the spermatogonia will have undergone about 660 such divisions, compared to 200 at age 20. [47] Copying errors might sometimes happen during the DNA replication preceding these cell divisions, which may lead to new (de novo) mutations in the sperm DNA. [14]

The selfish spermatogonial selection hypothesis proposes that the influence of spermatogonial mutations in older men is further enhanced because cells with certain mutations have a selective advantage over other cells. [47] [50] Such an advantage would allow the mutated cells to increase in number through clonal expansion. [47] [50] In particular, mutations that affect the RAS pathway, which regulates spermatogonial proliferation, appear to offer a competitive advantage to spermatogonial cells, while also leading to diseases associated with paternal age. [50]

Epigenetic changes Edit

The production of sperm cells involves DNA methylation, an epigenetic process that regulates the expression of genes. [47] Improper genomic imprinting and other errors sometimes occur during this process, which can affect the expression of genes related to certain disorders, increasing the offspring's susceptibility. The frequency of these errors appears to increase with age. This could explain the association between paternal age and schizophrenia. [51] Paternal age affects offspring's behavior, possibly via an epigenetic mechanism recruiting a transcriptional repressor REST. [52]

Semen Edit

A 2001 review on variation in semen quality and fertility by male age concluded that older men had lower semen volume, lower sperm motility, and a decreased percent of normal sperm. [43]

A 2014 review indicated that increasing male age is associated with declines in many semen traits, including semen volume and percentage motility. However, this review also found that sperm concentration did not decline as male age increased. [53]

X-linked effects Edit

Some classify the paternal age effect as one of two different types. One effect is directly related to advanced paternal age and autosomal mutations in the offspring. The other effect is an indirect effect in relation to mutations on the X chromosome which are passed to daughters who are then at risk for having sons with X-linked diseases. [54]

Birth defects were acknowledged in the children of older men and women even in antiquity. In book six of Plato's Republic, Socrates states that men and women should have children in the "prime of their life" which is stated to be twenty in a woman and thirty in a man. He states that in his proposed society men should be forbidden to father children in their fifties and that the offspring of such unions should be considered "the offspring of darkness and strange lust." He suggests appropriate punishments be administered to the offenders and their offspring. [55] [56]

In 1912, Wilhelm Weinberg, a German physician, was the first person to hypothesize that non-inherited cases of achondroplasia could be more common in last-born children than in children born earlier to the same set of parents. [57] Weinberg "made no distinction between paternal age, maternal age and birth order" in his hypothesis. In 1953, Krooth used the term "paternal age effect" in the context of achondroplasia, but mistakenly thought the condition represented a maternal age effect. [57] [58] : 375 The paternal age effect for achondroplasia was described by Lionel Penrose in 1955. At a DNA level, the paternal age effect was first reported in 1998 in routine paternity tests. [59]

Scientific interest in paternal age effects is relevant because the average paternal age increased in countries such as the United Kingdom, [60] Australia [61] and Germany, [62] and because birth rates for fathers aged 30–54 years have risen between 1980 and 2006 in the United States. [63] Possible reasons for the increases in average paternal age include increasing life expectancy and increasing rates of divorce and remarriage. [62] Despite recent increases in average paternal age, however, the oldest father documented in the medical literature was born in 1840: George Isaac Hughes was 94 years old at the time of the birth of his son by his second wife, a 1935 article in the Journal of the American Medical Association stated that his fertility "has been definitely and affirmatively checked up medically," and he fathered a daughter in 1936 at age 96. [62] [64] [65] In 2012, two 96-year-old men, Nanu Ram Jogi and Ramjit Raghav, both from India, claimed to have fathered children that year. [66]

The American College of Medical Genetics recommends obstetric ultrasonography at 18–20 weeks gestation in cases of advanced paternal age to evaluate fetal development, but it notes that this procedure "is unlikely to detect many of the conditions of interest." They also note that there is no standard definition of advanced paternal age [11] it is commonly defined as age 40 or above, but the effect increases linearly with paternal age, rather than appearing at any particular age. [67] According to a 2006 review, any adverse effects of advanced paternal age "should be weighed up against potential social advantages for children born to older fathers who are more likely to have progressed in their career and to have achieved financial security." [60]

Geneticist James F. Crow described mutations that have a direct visible effect on the child's health and also mutations that can be latent or have minor visible effects on the child's health many such minor or latent mutations allow the child to reproduce, but cause more serious problems for grandchildren, great-grandchildren and later generations. [6]


Contents

1980s Edit

The first study of what would come to be called aDNA was conducted in 1984, when Russ Higuchi and colleagues at the University of California, Berkeley reported that traces of DNA from a museum specimen of the Quagga not only remained in the specimen over 150 years after the death of the individual, but could be extracted and sequenced. [5] Over the next two years, through investigations into natural and artificially mummified specimens, Svante Pääbo confirmed that this phenomenon was not limited to relatively recent museum specimens but could apparently be replicated in a range of mummified human samples that dated as far back as several thousand years. [6] [7] [8]

The laborious processes that were required at that time to sequence such DNA (through bacterial cloning) were an effective brake on the development of the field of ancient DNA (aDNA). However, with the development of the Polymerase Chain Reaction (PCR) in the late 1980s, the field began to progress rapidly. [9] [10] Double primer PCR amplification of aDNA (jumping-PCR) can produce highly skewed and non-authentic sequence artifacts. Multiple primer, nested PCR strategy was used to overcome those shortcomings.

1990s Edit

The post-PCR era heralded a wave of publications as numerous research groups claimed success in isolating aDNA. Soon a series of incredible findings had been published, claiming authentic DNA could be extracted from specimens that were millions of years old, into the realms of what Lindahl (1993b) has labelled Antediluvian DNA. [11] The majority of such claims were based on the retrieval of DNA from organisms preserved in amber. Insects such as stingless bees, [12] [13] termites, [14] and wood gnats, [15] [ full citation needed ] as well as plant [16] and bacterial [17] sequences were said to have been extracted from Dominican amber dating to the Oligocene epoch. Still older sources of Lebanese amber-encased weevils, dating to within the Cretaceous epoch, reportedly also yielded authentic DNA. [18] Claims of DNA retrieval were not limited to amber.

Reports of several sediment-preserved plant remains dating to the Miocene were published. [19] [20] Then in 1994, Woodward et al. reported what at the time was called the most exciting results to date [21] — mitochondrial cytochrome b sequences that had apparently been extracted from dinosaur bones dating to more than 80 million years ago. When in 1995 two further studies reported dinosaur DNA sequences extracted from a Cretaceous egg, [22] [23] it seemed that the field would revolutionize knowledge of the Earth's evolutionary past. Even these extraordinary ages were topped by the claimed retrieval of 250-million-year-old halobacterial sequences from halite. [24] [25]

The development of a better understanding of the kinetics of DNA preservation, the risks of sample contamination and other complicating factors led the field to view these results more skeptically. Numerous careful attempts failed to replicate many of the findings, and all of the decade's claims of multi-million year old aDNA would come to be dismissed as inauthentic. [26]

2000s Edit

Single primer extension amplification was introduced in 2007 to address postmortem DNA modification damage. [27] Since 2009 the field of aDNA studies has been revolutionized with the introduction of much cheaper research-techniques. [28] The use of high-throughput Next Generation Sequencing (NGS) techniques in the field of ancient DNA research has been essential for reconstructing the genomes of ancient or extinct organisms. A single-stranded DNA (ssDNA) library preparation method has sparked great interest among ancient DNA (aDNA) researchers. [29] [30]

In addition to these technical innovations, the start of the decade saw the field begin to develop better standards and criteria for evaluating DNA results, as well as a better understanding of the potential pitfalls. [26] [31]

Degradation processes Edit

Due to degradation processes (including cross-linking, deamination and fragmentation) ancient DNA is of lower quality in comparison with modern genetic material. [3] The damage characteristics and ability of aDNA to survive through time restricts possible analyses and places an upper limit on the age of successful samples. [3] There is a theoretical correlation between time and DNA degradation, [32] although differences in environmental conditions complicates things. Samples subjected to different conditions are unlikely to predictably align to a uniform age-degradation relationship. [33] The environmental effects may even matter after excavation, as DNA decay rates may increase, [34] particularly under fluctuating storage conditions. [35] Even under the best preservation conditions, there is an upper boundary of 0.4–1.5 million years for a sample to contain sufficient DNA for contemporary sequencing technologies. [4]

Research into the decay of mitochondrial and nuclear DNA in Moa bones has modelled mitochondrial DNA degradation to an average length of 1 base pair after 6,830,000 years at −5 °C. [3] The decay kinetics have been measured by accelerated aging experiments further displaying the strong influence of storage temperature and humidity on DNA decay. [36] Nuclear DNA degrades at least twice as fast as mtDNA. As such, early studies that reported recovery of much older DNA, for example from Cretaceous dinosaur remains, may have stemmed from contamination of the sample.

Age limit Edit

A critical review of ancient DNA literature through the development of the field highlights that few studies after about 2002 have succeeded in amplifying DNA from remains older than several hundred thousand years. [37] A greater appreciation for the risks of environmental contamination and studies on the chemical stability of DNA have resulted in concerns being raised over previously reported results. The alleged dinosaur DNA was later revealed to be human Y-chromosome, [38] while the DNA reported from encapsulated halobacteria has been criticized based on its similarity to modern bacteria, which hints at contamination. [31] A 2007 study also suggests that these bacterial DNA samples may not have survived from ancient times, but may instead be the product of long-term, low-level metabolic activity. [39]

aDNA may contain a large number of postmortem mutations, increasing with time. Some regions of polynucleotide are more susceptible to this degradation, so sequence data can bypass statistical filters used to check the validity of data. [26] Due to sequencing errors, great caution should be applied to interpretation of population size. [40] Substitutions resulting from deamination of cytosine residues are vastly over-represented in the ancient DNA sequences. Miscoding of C to T and G to A accounts for the majority of errors. [41]

Contamination Edit

Another problem with ancient DNA samples is contamination by modern human DNA and by microbial DNA (most of which is also ancient). [42] [43] New methods have emerged in recent years to prevent possible contamination of aDNA samples, including conducting extractions under extreme sterile conditions, using special adapters to identify endogenous molecules of the sample (over ones that may have been introduced during analysis), and applying bioinformatics to resulting sequences based on known reads in order approximate rates of contamination. [44]

Despite the problems associated with 'antediluvian' DNA, a wide and ever-increasing range of aDNA sequences have now been published from a range of animal and plant taxa. Tissues examined include artificially or naturally mummified animal remains, [5] [45] bone, [46] [47] [48] [49] paleofaeces, [50] [51] alcohol preserved specimens, [52] rodent middens, [53] dried plant remains, [54] [55] and recently, extractions of animal and plant DNA directly from soil samples. [56]

In June 2013, a group of researchers including Eske Willerslev, Marcus Thomas Pius Gilbert and Orlando Ludovic of the Centre for Geogenetics, Natural History Museum of Denmark at the University of Copenhagen, announced that they had sequenced the DNA of a 560–780 thousand year old horse, using material extracted from a leg bone found buried in permafrost in Canada's Yukon territory. [57] [58] [59] A German team also reported in 2013 the reconstructed mitochondrial genome of a bear, Ursus deningeri, more than 300,000 years old, proving that authentic ancient DNA can be preserved for hundreds of thousand years outside of permafrost. [60] The DNA sequence of even older nuclear DNA was reported in 2021 from the permafrost-preserved teeth of two Siberian mammoths, both over a million years old. [61] [62]

Researchers in 2016 measured chloroplast DNA in marine sediment cores, and found diatom DNA dating back to 1.4 million years. [63] This DNA had a half-life significantly longer than previous research, of up to 15,000 years. Kirkpatrick's team also found that DNA only decayed along a half-life rate until about 100 thousand years, at which point it followed a slower, power-law decay rate. [63]

40,000 years that yielded genome-wide data [64]

Due to the considerable anthropological, archaeological, and public interest directed toward human remains, they have received considerable attention from the DNA community. There are also more profound contamination issues, since the specimens belong to the same species as the researchers collecting and evaluating the samples.

Sources Edit

Due to the morphological preservation in mummies, many studies from the 1990s and 2000s used mummified tissue as a source of ancient human DNA. Examples include both naturally preserved specimens, for example, those preserved in ice, such as the Ötzi the Iceman, [65] or through rapid desiccation, such as high-altitude mummies from the Andes, [8] [66] as well as various sources of artificially preserved tissue (such as the chemically treated mummies of ancient Egypt). [67] However, mummified remains are a limited resource. The majority of human aDNA studies have focused on extracting DNA from two sources that are much more common in the archaeological record – bone and teeth. The bone that is most often used for DNA extraction is the petrous bone, since its dense structure provides good conditions for DNA preservation. [68] Several other sources have also yielded DNA, including paleofaeces, [69] and hair. [70] [71] Contamination remains a major problem when working on ancient human material.

Ancient pathogen DNA has been successfully retrieved from samples dating to more than 5,000 years old in humans and as long as 17,000 years ago in other species. In addition to the usual sources of mummified tissue, bones and teeth, such studies have also examined a range of other tissue samples, including calcified pleura, [72] tissue embedded in paraffin, [73] [74] and formalin-fixed tissue. [75] Efficient computational tools have been developed for pathogen and microorganism aDNA analyses in a small (QIIME [76] ) and large scale (FALCON [77] ).

Results Edit

Taking preventative measures in their procedure against such contamination though, a 2012 study analyzed bone samples of a Neanderthal group in the El Sidrón cave, finding new insights on potential kinship and genetic diversity from the aDNA. [78] In November 2015, scientists reported finding a 110,000-year-old tooth containing DNA from the Denisovan hominin, an extinct species of human in the genus Homo. [79] [80]

The research has added new complexity to the peopling of Eurasia. It has also revealed new information about links between the ancestors of Central Asians and the indigenous peoples of the Americas. In Africa, older DNA degrades quickly due to the warmer tropical climate, although, in September 2017, ancient DNA samples, as old as 8,100 years old, have been reported. [81]

Moreover, ancient DNA has helped researchers to estimate modern human divergence. [82] By sequencing African genomes from three Stone Age hunter gatherers (2000 years old) and four Iron Age farmers (300 to 500 years old), Schlebusch and colleagues were able to push back the date of the earliest divergence between human populations to 350,000 to 260,000 years ago.


Why Do We Age?

Programmed in our genes

The pros

  • Single genes have been found that increase life span in Drosophila, C. elegans, and mice. Genes that suppress signaling by insulin and insulin-like growth factor-1 (Igf-1) increase life span in these animals. Examples:
    • Mice with one of their Igf-1 receptor genes “knocked out” live 25% longer than normal mice.
    • Klotho. Cells in the kidney and brain release the extracellular portion of a cell surface transmembrane protein into the blood. This “hormone”, called Klotho, binds to receptors on many target cells reducing their ability to respond to insulin and Igf-1 signaling.
      • Mice homozygous for a mutantklotho gene show many signs of premature aging while
      • mice expressing extra-high levels of the Klotho protein live 20–30% longer than normal.
      • p53. By forcing cells with damaged DNA to stop dividing and become senescent or even to die by apoptosis, it protects the organism from the threat of those cells becoming cancerous but at the expense of reducing cell renewal (e.g., by decreasing the size of the pools of stem cells). Mice that are forced to produce higher-than-normal levels of the p53 protein show many signs of premature aging while female mice that are deficient in p53 have reduced fecundity (blastocysts fail to implant). So here is a tradeoff by a gene that promotes evolutionary success at an early age but at the expense of accelerated aging.
      • In both Drosophila and C. elegans, some mutations that increase life span do so at the cost of decreased fecundity and vice versa.
      • any genes that extend the reproductive period or
      • any genes that promote fitness in youth as well as longevity would be selected for.

      The cons

      High early mortality from external causes (e.g. predators) has been linked to early aging (in the survivors) in some animals, but the reverse has been found in others. These contradictory results do not negate the role of genes in aging, but indicate that other environmental factors (e.g. more food left for the survivors) may skew the outcome.


      Epigenetic Alterations

      A variety of epigenetic alterations affects all cells and tissues throughout life (Talens et al., 2012) ( Figure 2B ). Epigenetic changes involve alterations in DNA methylation patterns, post-translational modification of histones, and chromatin remodeling. Increased histone H4K16 acetylation, H4K20 trimethylation or H3K4 trimethylation, as well as decreased H3K9 methylation or H3K27 trimethylation, constitute age-associated epigenetic marks (Fraga and Esteller, 2007 Han and Brunet, 2012). The multiple enzymatic systems assuring the generation and maintenance of epigenetic patterns include DNA methyltransferases, histone acetylases, deacetylases, methylases and demethylases, as well as protein complexes implicated in chromatin remodeling.

      Histone modifications

      Histone methylation meets the criteria for a hallmark of aging in invertebrates. Deletion of components of histone methylation complexes extends longevity in nematodes and flies (Greer et al., 2010 Siebold et al., 2010). Moreover, histone demethylases modulate lifespan by targeting components of key longevity routes such as the insulin/IGF-1 signaling pathway (Jin et al., 2011). It is not clear yet whether manipulations of histone-modifying enzymes can influence aging through purely epigenetic mechanisms, by impinging on DNA repair and genome stability, or through transcriptional alterations affecting metabolic or signaling pathways outside of the nucleus.

      The sirtuin family of NAD-dependent protein deacetylases and ADP-ribosyltransferases has been studied extensively as potential anti-aging factors. Interest in this family of proteins in relation to aging stems from a series of studies in yeast, flies and worms reporting that the single sirtuin gene of these organisms, named Sir2, had a remarkable longevity activity (Guarente, 2011). Overexpression of Sir2 was first shown to extend replicative lifespan in Saccharomyces cerevisiae (Kaeberlein et al., 1999), and subsequent reports indicated that enhanced expression of the worm (sir-2.1) and fly (dSir2) orthologs could extend lifespan in both invertebrate model systems (Rogina and Helfand, 2004 Tissenbaum and Guarente, 2001). These findings have recently been called into question, however, with the report that the lifespan extension originally observed in the worm and fly studies was mostly due to confounding genetic background differences and not to the overexpression of sir-2.1 or dSir2, respectively (Burnett et al., 2011). In fact, careful reassessments indicate that overexpression of sir-2.1 only results in modest lifespan extension in C. elegans (Viswanathan and Guarente, 2011).

      Regarding mammals, several studies have shown that several of the seven mammalian sirtuins can delay various parameters of aging in mice (Houtkooper et al., 2012 Sebastian et al., 2012). In particular, transgenic overexpression of mammalian SIRT1, which is the closest homologue to invertebrate Sir2, improves aspects of health during aging but does not increase longevity (Herranz et al., 2010). The mechanisms involved in the beneficial effects of SIRT1 are complex and interconnected, including a wide range of cellular actions from improved genomic stability (Oberdoerffer et al., 2008 Wang et al., 2008) to enhanced metabolic efficiency (Nogueiras et al., 2012) (see also Deregulated Nutrient-sensing). More compelling evidence for a sirtuin-mediated pro-longevity role in mammals has been obtained for SIRT6, which regulates genomic stability, NF-㮫 signaling and glucose homeostasis through histone H3K9 deacetylation (Kanfi et al., 2010 Kawahara et al., 2009 Zhong et al., 2010). Mutant mice deficient in SIRT6 exhibit accelerated aging (Mostoslavsky et al., 2006), whereas male transgenic mice overexpressing Sirt6 have a longer lifespan than control animals, associated with reduced serum IGF-1 and other indicators of IGF-1 signaling (Kanfi et al., 2012). Interestingly, the mitochondria-located SIRT3 has been reported to mediate some of the beneficial effects of dietary restriction (DR) in longevity, although its effects are not due to histone modifications but to the deacetylation of mitochondrial proteins (Someya et al., 2010). Very recently, overexpression of SIRT3 has been reported to reverse the regenerative capacity of aged hematopoietic stem cells (Brown et al., 2013). Therefore, in mammals, at least three members of the sirtuin family, SIRT1, SIRT3 and SIRT6, contribute to healthy aging.

      DNA methylation

      The relationship between DNA methylation and aging is complex. Early studies described an age-associated global hypomethylation, but subsequent analyses revealed that several loci, including those corresponding to various tumor suppressor genes and Polycomb target genes, actually become hypermethylated with age (Maegawa et al., 2010). Cells from patients and mice with progeroid syndromes exhibit DNA methylation patterns and histone modifications that largely recapitulate those found in normal aging (Osorio et al., 2010 Shumaker et al., 2006). All of these epigenetic defects or epimutations accumulated throughout life may specifically affect the behavior and functionality of stem cells (Pollina and Brunet, 2011) (see section on Stem Cell Exhaustion). Nevertheless, thus far there is no direct experimental demonstration that organismal lifespan can be extended by altering patterns of DNA methylation.

      Chromatin remodeling

      DNA- and histone-modifying enzymes act in concert with key chromosomal proteins, such as the heterochromatin protein 1α (HP1α), and chromatin remodeling factors, such as Polycomb group proteins or the NuRD complex, whose levels are diminished in both normally and pathologically aged cells (Pegoraro et al., 2009 Pollina and Brunet, 2011). Alterations in these epigenetic factors together with the above discussed epigenetic modifications in histones and DNA-methylation determine changes in chromatin architecture, such as global heterochromatin loss and redistribution, which constitute characteristic features of aging (Oberdoerffer and Sinclair, 2007 Tsurumi and Li, 2012). The causal relevance of these chromatin alterations in aging is supported by the finding that flies with loss-of-function mutations in HP1α have a shortened lifespan, whereas overexpression of this heterochromatin protein extends longevity in flies and delays the muscular deterioration characteristic of old age (Larson et al., 2012).

      Supporting the functional relevance of epigenetically-mediated chromatin alterations in aging, there is a notable connection between heterochromatin formation at repeated DNA domains and chromosomal stability. In particular, heterochromatin assembly at pericentric regions requires trimethylation of histones H3K9 and H4K20, as well as HP1α binding, and is important for chromosomal stability (Schotta et al., 2004). Mammalian telomeric repeats are also enriched for these chromatin modifications, indicating that chromosome ends are assembled into heterochromatin domains (Gonzalo et al., 2006). Subtelomeric regions also show features of constitutive heterochromatin including H3K9 and H4K20 trimethylation, HP1α binding, and DNA hypermethylation. Thus, epigenetic alterations can directly impinge on the regulation of telomere length, one of the hallmarks of aging. Moreover, in response to DNA damage, SIRT1 and other chromatin-modifying proteins relocalize to DNA breaks to promote repair and genomic stability (Oberdoerffer et al., 2008). Beyond its role in chromatin remodeling and DNA repair, SIRT1 also modulates proteostasis, mitochondrial function, nutrient-sensing pathways and inflammation (see below), illustrating the interconnectedness between aging hallmarks.

      Transcriptional alterations

      Aging is associated with an increase in transcriptional noise (Bahar et al., 2006), and an aberrant production and maturation of many mRNAs (Harries et al., 2011 Nicholas et al., 2010). Microarray-based comparisons of young and old tissues from several species have identified age-related transcriptional changes in genes encoding key components of inflammatory, mitochondrial and lysosomal degradation pathways (de Magalhaes et al., 2009). These aging-associated transcriptional signatures also affect non-coding RNAs, including a class of miRNAs (gero-miRs) that is associated with the aging process and influences lifespan by targeting components of longevity networks or by regulating stem cell behavior (Boulias and Horvitz, 2012 Toledano et al., 2012 Ugalde et al., 2011). Gain- and loss-of-function studies have confirmed the capacity of several miRNAs to modulate longevity in Drosophila melanogaster and C. elegans (Liu et al., 2012 Shen et al., 2012 Smith-Vikos and Slack, 2012).

      Reversion of epigenetic changes

      Unlike DNA mutations, epigenetic alterations are – at least theoretically – reversible, hence offering opportunities for the design of novel anti-aging treatments (Freije and Lopez-Otin, 2012 Rando and Chang, 2012). Restoration of physiological H4 acetylation through administration of histone deacetylase inhibitors, avoids the manifestation of age-associated memory impairment in mice (Peleg et al., 2010), indicating that reversion of epigenetic changes may have neuroprotective effects. Inhibitors of histone acetyltransferases also ameliorate the premature aging phenotype and extend longevity of progeroid mice (Krishnan et al., 2011). Moreover, the recent discovery of transgenerational epigenetic inheritance of longevity in C. elegans suggests that manipulation of specific chromatin modifications in parents can induce an epigenetic memory of longevity in their descendants (Greer et al., 2011). Conceptually similar to histone acetyltransferase inhibitors, histone deacetylase activators may conceivably promote longevity. Resveratrol has been extensively studied in relation to aging and among its multiple mechanisms of action is the upregulation of SIRT1 activity, but also other effects associated with energetic deficits (see Mitochondrial Dysfunction).

      Overview

      There are multiple lines of evidence suggesting that aging is accompanied by epigenetic changes, and that epigenetic perturbations can provoke progeroid syndromes in model organisms. Furthermore, SIRT6 exemplifies an epigenetically relevant enzyme whose loss-of-function reduces longevity and whose gain-of-function extends longevity in mice (Kanfi et al., 2012 Mostoslavsky et al., 2006). Collectively, these works suggest that understanding and manipulating the epigenome holds promise for improving age-related pathologies and extending healthy lifespan.


      Older Dads’ Kids at Higher Risk for Genetic Disease

      Over the last few years, it has become apparent that older dads have kids with more genetic diseases than younger dads. This is clearest for simpler diseases like dwarfism or Apert syndrome. But newer data is pointing towards an increased risk for more complex diseases like autism and schizophrenia too.

      A big reason for this is highlighted in a new study out in Nature that shows that the older the dad, the more mutations he passes down to his kids. They were able to calculate that for every year older, a dad will pass on an average of two new mutations to his child. Mom’s age didn’t affect the number of mutations much at all and she contributed fewer mutations to her kids no matter what her age.

      Most of the time dad’s extra mutations don’t much matter. The DNA changes are in parts of our DNA that don’t do a whole lot. Or the mutation doesn’t muck up anything important.

      But sometimes they do matter. Occasionally a mutation will happen in an important part of the DNA in such a way as to lead to disease. This is the main reason the children of older dads are at a higher risk for certain genetic diseases --their dad gave them old, battered DNA.

      This isn’t enough to explain the increased risk for these diseases though. While older dads do pass on more mutations, the number isn’t high enough to explain the high incidence of these genetic diseases. There are too few mutations spread out over way too much DNA. No, something else must be going on.

      In a recent review in The American Journal of Human Genetics, the authors float the idea that certain mutations give advantages to the sperm in its testicular environment. So the sperm are busy making copies of themselves to be sent out in search of an egg. Occasionally one gets a mutation that makes it heartier in some way and so it out competes its brethren. Now it becomes more common.

      Unfortunately, what makes a hearty sperm might make for an ill child. The environment for a single cell in a testicle is obviously very different from a whole person out in the world! The authors argue that some mutations that lead to disease can be useful for single sperm.

      If true, these findings can explain a lot. And they suggest big changes for human DNA in future generations.

      Both men and women are waiting to have children later in life. That means an increase in the number of mutations being passed down to the next generation. This might help to explain at least part of the increase in autism in the U.S. and Europe.

      Older dads also means the mutation rate for humans is accelerating. Humans will more quickly become genetically diverse than they might have in the past.

      Now despite the scary sound of the word mutation, this isn’t necessarily a bad thing. Mutations are where all the genetic diversity in the human race ultimately came from. And the more diverse humans are, the more likely they are to survive some new biological threat.

      But if the selfish sperm hypothesis is true, older dads will also mean a build up of whatever DNA changes are good for making sperm. Remember, what’s good for the sperm isn’t necessarily good for everyone else.

      Any mutations that lead to major disease are not the big problem evolutionarily speaking (although they can obviously be devastating individually). These mutations do not tend to get passed on.

      Where these mutations become a problem is when they have minor negative effects on people. Because of the advantage to the sperm, these slightly harmful mutations may get passed on more often and become more common in the population. Even though their main advantage is to the individual sperm!

      Until recently, all the focus was on older moms and their increased chances for having children with big DNA problems. Now the focus is widening to include older dads. Even though their changes are smaller, they can still have big effects.


      Researchers do not agree as to the causes of aging. Some claim our genes are programmed to deteriorate, wither and die, while others believe accumulated damage is the root of our senescence. Muddying the waters further, many believe that a combination of several factors contributes to aging.

      Cell Damage

      Around since 1882 when biologist August Weismann first introduced it, at its fundamental level, the cell damage theory holds that the body succumbs to “wear and tear“: “Like components of an aging car, parts of the body eventually wear out from repeated use, killing them and then the body.”

      Building on this fundamental idea, a number of researchers today are exploring particular physiological aspects to reveal where and how this “wear and tear” occurs.

      Somatic DNA Damage

      Focusing on the deterioration of DNA over a lifetime, according to this theory:

      DNA damages occur continuously in cells . . . . While most of these damages are repaired, some accumulate . . . . [and] genetic mutations occur and accumulate with increasing age, causing cells to deteriorate and malfunction. In particular, damage to mitochondrial DNA might lead to . . . dysfunction. . . [where] aging results from damage to the genetic integrity of the body’s cells.

      Mitochondrial DNA (mtDNA) mutate faster than DNA in a cell nucleus, so mtDNA create more damaging “free radicals” that are believed to induce aging. Given that mitochondria (the power plants of cells) work harder the more fuel (a.k.a. “food”) is available, the less an organism eats, the fewer free radicals are produced. As a result, some scientists have opined that calorie restriction (CR) can act as a fountain of youth: “A diet severely restricted in calories (about 30 percent below normal, but above starvation levels) can increase lifespan, lower rates of cancer, and slow declines in memory and movement.”

      Others are more cautious when it comes to recommending a CR diet: “Restricted-diet animals grow more slowly, reproduce less, and have dampened immune systems . . . [because the] dietary restriction seems to switch the body into a survival mode in which growth and energy consumption are suppressed.”

      In addition, detractors note that just because: “Lifespan extensions [were] seen in mice [this] may not be observed in large mammals like humans . . . [because unlike small animals] large mammals can migrate in times of famine . . . .”

      Nonetheless, at least one study has shown that people on a CR diet will “lower blood cholesterol and insulin and . . . reduce[ the] risk of atherosclerosis,” all conditions that contribute to aging and mortality.

      Cross-Linking

      Another branch of the cell damage theory focuses on “cross-linking,” a process whereby damaged and obsolete proteins, which would otherwise be broken down by enzymes (proteases), are protected from that action by making inappropriate attachments, allowing them to “stick around and . . . cause problems.” Over time: “An accumulation of cross-linked proteins damages cells and tissues, slowing down bodily processes . . . .”

      This phenomenon has been identified in at least one sign of aging, and implicated in another:

      Cross-linking of the skin protein collagen, for example, has proven at least partly responsible for wrinkling and other age-related dermal changes [and] . . . in the lens of the eye is also believed to play a role in age-related cataract formation. Researchers speculate that cross-linking of proteins in the walls of arteries or the filter systems of the kidney account for at least some of . . . atherosclerosis . . . .

      Genetic Coding

      Looking at the blueprints that drive organisms, each of these theories explores the idea that, at the cellular level, we are “programmed” for obsolescence.

      Programmed Longevity

      Many researchers believe that: “Aging is the result of a sequential switching on and off of certain genes, with senescence [old age] being defined as the time when age-associated deficits are manifested . . . .”

      To support this theory, scientists have studied aging with the help of Caenorhabditis elegans: “The classic laboratory nematode . . . [which are] tiny, transparent worms . . . [that are] easy to manipulate genetically, and with a life span of just two weeks . . . provide a quick time-lapse view of the aging process . . . .”

      In 1993, one group of researchers discovered that: “C. elegans with a specific single-gene mutation lived twice as long as members of the species that lacked [it. This] . . . led to a shift in thinking . . . that [as opposed to many genes] a single gene could dramatically regulate how long an organism lived . . . .”

      This gene, daf-2, is a protein remarkably similar to our receptor protein insulin, and, at least in C. elegans, was shown in later research to be a very bossy gene: “Daf-2 normally controls many other genes . . . . For example, in their studies of C. Elegans, researchers have found a large set of genes that are either “turned on” or “turned off” in worms that carry two copies of the daf-2 mutation . . . .”

      The types of genes that are regulated by daf-2 include stress resistance, development and metabolism. This is significant because these: “Various genes encode for proteins that extend life by acting as antioxidants, regulating metabolism and exerting an antibacterial effect . . . .”

      Endocrine Theory

      Other researchers ascribe to the theory that age-regulating genes carry: “Biological clocks [that] act through hormones to control the pace of aging [through] . . . the evolutionarily conserved insulin/IGF-1 signaling (IIS) pathway . . . .”

      This signaling pathway is significant: “The IIS system is an ancient system that is highly conserved and coordinates growth, differentiation and metabolism in response to changing environmental conditions and nutrient availability . . .”

      Thus, under this theory, individuals adapt at a cellular level, in response to environmental conditions, to foster the best outcome for continuation of the species: “In response to harsh environmental conditions . . . [cells adapt to produce] enhancement of cellular stress resistance and protection, suppression of low-grade inflammation and enhanced mitochondrial biogenesis [increased energy in the cell].”

      Thus, in tough times the organism’s life is extended, at least long enough for it to fulfill its biological imperative to breed.

      Immunological Theory

      The third gene-coding proposal to explain aging provides that: “The immune system is programmed to decline over time, which leads to an increased vulnerability to infectious disease and thus aging and death.”

      Proponents of this theory note that: “As one grows older, antibodies lose their effectiveness, and fewer new diseases can be combated effectively by the body, which causes cellular stress and eventual death.”

      This last argument has been called into question by recent research that studied mortality and fertility across 46 different species (including humans), which produced remarkable results: “Although . . . most of the 46 species can be roughly classified along a continuum of senescence . . . [displaying] strong deterioration with age [other species demonstrated] negative deterioration, to negative senescence and improvement with age.”

      This means that unlike people, some species: “Are the opposite of humans, becoming more likely to reproduce and less likely to die with each passing year.

      In fact, there is so much diversity of aging across species that, even among those that age like us, there are some, such as the alpine swift, that become more fertile (likely to reproduce) as they approach their demise.

      If you liked this article, you might also enjoy our new popular podcast, The BrainFood Show (iTunes, Spotify, Google Play Music, Feed), as well as:

      40 comments

      No, no and no. All wrong. We age because God hates us.

      Well, He hates you. Me he’s just indifferent toward.

      well actually, we age because of the way DNA replicates. Think if it this way- when you are born, you have a fresh code of DNA, and because it hasn’t replicated a lot yet, it is very “long.” Everytime DNA replicates, it gets smaller. Somatic and other cells will keep dividing until DNA is too short to divide correctly without problems. That point is ageing. Although we have enzymes that extend our DNA, such as trees have, this “fake” DNA only extends for replication, it is not viable coding for anything.

      so if you can sequence a person’s DNA at a certain age, you can generate new stem cells with young DNA and prevent aging.

      This is correct, I think that’s why this article talks about bad funtion of dna, iven they don’t say nothing about it here, but thats the reason of why in some point of a long life our organs don’t work right.

      When we are young, we live the moment and we think that moment is our eternity and we will live forever (this helps!) when we get old, we miss those past moments and we think we have no more, we think that the current moment is the last one and that it is too short, and we will die soon.
      We are a machine that reconstructs itself every moment using food energy as the rebuilding blocks. With this hard work everyday, some mechanisms of that machine eventually breaks and becomes unable to reconstruct itself. It ages. If it is an important mechanism in the whole system, a dominoe effect is triggered and the whole body is comprimised. Take the heart, for instance. If it does not feed itself with oxigenated blood in the first place, it degrades quickly and takes the whole body away with it.
      I believe that thinking positively (as the young ones that think they will live forever) is a kind of fuel that helps to regenerate our bodies. Those who think negatively (like some elders) have a broken mechanism already (but they can fix it, if they wish).

      The only way to stop aging is by placing the reconstructing system outside the body. One part of this system is, in some way, outside the body and, currently, it is the only one we have at our disposal to help us to live longer: our mind. Try it.

      Over the lifespan of an individual, human body cells have the ability to regenerate the tissues. The regenerative power of tissues and organs declines as we age. Adult stem cells are important as it keeps human tissues healthy by replacing old and damaged cells accumulated over time.This is because of the DNA at the end of chromosomes called telomeres that get shorter with each division. When they run out, the cell dies. As you can see, aging is mostly due to the short span of cells regenerative.

      The reasons of aging happens in our body?

      The number of stem cells reduces due to environmental factors, among others, mental depression and malnutrition. Decreasing number of stem cells also results in a number of age-related diseases. With Mesenchymal stem cells therapy, the new and young cells will repair and regenerate your body, thereby creating better health benefits.

      (Side Note: Mesenchymal stem cells (MSCs) are multipotent cells which have the unique ability of self-renewal. MSCs also divide and proliferate throughout the lifetime of an individual.)

      Wharton Jelly of the umbilical cord has been found to be rich in MSCs and it tends to be the most primitive stromal population in the human body. These attributes could potentially be harnessed to increase our body’s defence mechanism. They are also beneficial in terms of enhancement of immune system, prevention of diseases, better organ health and even anti-ageing process.

      These attributes also help divide and differentiate into a variety of mesenchymal tissues. The mesenchymal tissues include adipose tissues, tendons and ligaments, skeletal muscle tissues, bone and cartilage tissues and etc. Current stem cell research is generating strong evidences about how healthy stem cells, when under the right conditions or signals, could give rise to differentiated cells. It helps repair a host of ailments that occur because of tissue damage as people age.

      Ageing is essential for organisms to continue to evolve over time in response to environmental change. If a species didn’t age then parents would normally out compete with their offspring because they would be better at finding food, shelter and avoiding predation. This would slow the small incremental changes that occur in populations over time due to evolution as a result of mutations. This is less of a disadvantage for populations living in a stable environment but if predators can evolve faster than some of their prey species then those slower evolving species may die out altogether.

      This is in the same way that animals that are large in size that may only have one offspring every one or two years can’t respond as quickly to environmental change as those species that produce larger numbers of offspring and as a result have a greater chance of favourable mutations.

      We are supposed to live forever but we are dying because of sin. We are spiritual beings and there is a creator. God created everything for his purpose and glory. God created us in his image and likeness. He loves us so much that he does not want us to perish eternally because of sin. For God so loved the world that he gave his one and only son Jesus, for whoever so believes in Him shall not perish but have eternal life. Jesus says .. “I am the way, the truth, and the life. No one comes to the father except thru me”…God loves you and me. If we repent of our sins and accept Jesus as our Lord , we will live forever. Physically we will die because of sin but if we repent and trust in Jesus we will not spend eternity in Hell but in Heaven. There will come a time when we will have new bodies made for eternity. Don’t miss out on this gift that God offers you. Your choice …Heaven or Hell? God loves you and He wants you to be in Heaven , a better place. He does not want you to be in Hell. Don’t miss out on this….repent from your sin and trust and follow Jesus..this is the only answerbto what your searching for. You can explain all life forms or dna but God made all these, so don’t miss out on Jesus…


      Age is not a number, it’s a cellular morphology

      Dermal fibroblasts derived from a healthy 85-year-old donor stained for F-actin (green) and DNA (blue). Image shows the presence of both senescent and non-senescent cells in 2D cell cultures.

      They say you are only as old as you feel. The truth is you are as old as your cell morphology dictates. Jude Phillip, an assistant professor at Johns Hopkins University, thinks a lot about aging and has been pondering the questions: “Can we determine a person’s age based on the properties of their cells? Is aging information encoded in cells?”

      In his talk at Cell Bio Virtual 2020, “Defining Cell-based Biomarkers of Aging,” he reminded his audience that U.S. Census data indicate that by the year 2050, the population of adults over the age of 65 will double. This means that 20% of the U.S. population will be over the age of 60, he said.

      While so many folks are living longer, their quality of life may be poor, Phillip said. Science should turn its attention to studying aging in new ways to address the problems of getting older, such as frailty and the onset of disease.

      “Why should we live longer if we are sick and unhealthy when we could live longer being healthy and resilient?” Phillip said.

      Phillip approaches his inquiry into aging as a question of length scales. There is the macro-length scale (the epidemiological level), the scale of tissues and organs, down to the micro- or nano-scales (the cells and the genes). Rather than study aging only at the tissue or organ level or even at the genetic or molecular level, Phillip’s lab has taken the middle road—evaluating age at the level of a single cell. He said the morphology of the cells themselves is kind of the “missing link” between what one observes in a patient at a clinic and what one might discover through genetic analysis.

      Questions on aging span these length scales, Phillip said. “How are external disease manifestations impacted by changes at the cellular or molecular level, and what impact do they have on these smaller length scales?” is an overarching theme of his work.

      “Cells are integrators of molecular signals,” Phillip said. “If there is a defect at the molecular or genetic level, it will be integrated into the cell, and then propagated by the cells across tissues and organs and ultimately manifest as disease.”

      For his work, Phillip used dermal fibroblasts from healthy individuals age 2–96. The cells were collected as part of the Baltimore Longitudinal Study on Aging. Phillip then examined the correlation between the cell’s age (based on the age of the person it was taken from) and the biomolecular and biophysical properties quantified. His lab used high-throughput technologies to analyze individual cells. Some of the biomolecular properties observed included what proteins they secreted, their ATP production levels, changes in the cytoskeleton, their ability to repair DNA damage, and DNA organization. Some of the biophysical properties considered included cell shape (morphology), motility, mechanics, and traction strength. A total of 208 properties were considered.

      In a previously published study, Phillip reported that of the biomolecular features, ATP production was the most strongly correlated with age. However, his more recent findings indicate that the biophysical properties of cell morphology and motility are perhaps even more robust biomarkers of age. Phillip observed that cells lose motility with age. That is, they slow down, just like us! Phillip also noted that cell populations become more homogeneous with chronological age. That is, cell populations in older adults lose heterogeneity, Phillip said. This perhaps makes it harder for them to bounce back from stress or disease.

      “Our findings suggest that the quantification of cellular age may be used to stratify individuals on the basis of cellular phenotypes and serve as a biological proxy of healthspan,” Phillip said.

      Along with the normal, presumably healthy cells, Phillip also analyzed cells taken from those with Werner syndrome and Hutchinson–Gilford progeria syndrome, “two rare genetic conditions that result in phenotypes that show aspects of premature aging.” Cells with disease exhibited the properties of cells taken from chronologically older healthy individuals.

      Ultimately, Phillip said, understanding and predicting aging at the single-cell level could shape how medicine approaches treating the problems of old age. It could also have applications in developing precision medicine approaches that are tailored to meet an individual’s unique needs.


      ‘We still don’t know how to avoid frailty.’

      In sharp contrast, other experts argue that extending life span, even in the name of health, is a doomed pursuit. Perhaps the most common concern is the potential for overpopulation, especially considering humanity’s long history of hoarding and squandering resources and the tremendous socioeconomic inequalities that already divide a world of nearly eight billion. There are still dozens of countries where life expectancy is below 65, primarily because of problems like poverty, famine, limited education, disempowerment of women, poor public health and diseases like malaria and H.I.V./AIDS, which novel and expensive life-extending treatments will do nothing to solve.

      Lingering multitudes of superseniors, some experts add, would stifle new generations and impede social progress. “There is a wisdom to the evolutionary process of letting the older generation disappear,” said Paul Root Wolpe, the director of the Center for Ethics at Emory University, during one public debate on life extension. “If the World War I generation and World War II generation and perhaps, you know, the Civil War generation were still alive, do you really think that we would have civil rights in this country? Gay marriage?”

      In her final years at La Maison du Lac, the once-athletic Jeanne Calment was essentially immobile, confined to her bed and wheelchair. Her hearing continued to decline, she was virtually blind and she had trouble speaking. At times, it was not clear that she was fully aware of her surroundings.

      By some accounts, those in charge of Calment’s care failed to shield her from undue commotion and questionable interactions as journalists, tourists and spectators bustled in and out of her room. Following the release of an investigative documentary, the hospital director barred all visitors. The last time Robine saw her was shortly after her 120th birthday. About two years later, in the midst of an especially hot summer, Jeanne Calment died alone in her nursing-home room from unknown causes and was quickly buried. Only a few people were permitted to attend her funeral. Robine and Allard were not among them. Neither was Calment’s family: All her close relatives had been dead for more than three decades.

      “Today, more people are surviving the major diseases of old age and entering a new phase of their life in which they become very weak,” Robine said. “We still don’t know how to avoid frailty.”

      Perhaps the most unpredictable consequence of uncoupling life span from our inherited biology is how it would alter our future psychology. All of human culture evolved with the understanding that earthly life is finite and, in the grand scheme, relatively brief. If we are one day born knowing that we can reasonably expect to live 200 years or longer, will our minds easily accommodate this unparalleled scope of life? Or is our neural architecture, which evolved amid the perils of the Pleistocene, inherently unsuited for such vast horizons?

      Scientists, philosophers and writers have long feared that a surfeit of time would exhaust all meaningful experience, culminating in debilitating levels of melancholy and listlessness. Maybe the desire for all those extra years masks a deeper longing for something unattainable: not for a life that is simply longer, but for one that is long enough to feel utterly perfect and complete.

      In Jorge Luis Borges’s short story “The Immortal,” a Roman military officer stumbles upon a “secret river that purifies men of death.” After drinking from it and spending eons in deep thought, he realizes that death imbues life with value, whereas, for immortals, “Nothing can occur but once, nothing is preciously in peril of being lost.” Determined to find the antidote to everlasting life, he wanders the planet for nearly a millennium. One day, he drinks from a spring of clear water on the Eritrean coast and shortly thereafter scratches the back of his hand on a thorny tree. Startled by an unfamiliar twinge of pain, he searches for a sign of injury. As a drop of blood slowly pools on his skin — proof of his restored mortality — he simply watches, “incredulous, speechless, and in joy.”

      Ferris Jabr is a contributing writer for the magazine. His January 2019 cover story on the evolution of beauty is featured in the latest edition of The Best American Science and Nature Writing. Maurizio Cattelan is an Italian artist whose work has been the subject of numerous solo exhibitions, including shows at the Guggenheim Museum in New York and the Pompidou Center in Paris. Pierpaolo Ferrari is an Italian photographer and, along with Cattelan, is a co-founder of the magazine Toiletpaper, known for its surreal and humorous imagery.



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