Cordyceps Blog

Bolivian Amazon Cordyceps

Submitted by cordyceps on Wed, 03/27/2013 - 15:43

Cordyceps-diversity in the Amazon Rain Forest is impressive. Down below Cordyceps and allies we found during the February 2013 MushRoaming Bolivia Tour.
All specimens, unless otherwise noted were found in Madidi National Park or close by around Rurrenabaque. They are all deposited in the National Herbarium of Bolivia, La Paz. Special thanks to Tatiana Sanjuan, Bogota for help with identification.  All photos © Daniel Winkler

Cordyceps scarabaeicola



Close-up of the digested scarabaeid beetle.


Mature Cordyceps scarabaeicola with two stromata growing out of a scarabaeid beetle. Note how the two stromata are fused half way up.



Close-up of the fertile top of the stroma of Cordyceps scarabeicola. Several fertile cushions, in which perithecioid ascomata are immersed, are growing on top of the stroma.
 The superficial to partially immersed perithecia give the fruiting body of C. scarabeicola a much more irregular appearance, which is more common in Cordyceps than in Ophiocordyceps species.




   Cordyceps sp.  close to C. takaomontana



Cordyceps takaomontana? in Bolivia

In Mashaquipe we found one location so rich in Cordyceps it blew our minds. We called it "Cordyceps corner". There were about a dozen specimen of at least 5 genera. Most common was this Cordyceps that looks awfully like the East Asian Cordyceps takaomontana first described in Honshu, Japan. However, C. takaomontana was described to grow on coleopteran pupae and the host looks more like a larva.

The number of stromata growing from a leaf surface differed mightily from two to over ten. Interestingly at first, we could not see any insect hosts and were a bit perplexed. Then we realized all of them were leaf-insect sandwiches, the ham was a larva (see below).


Fruiting bodies growing out of both side of this "leaf sandwich".



Cordyceps takaomontana?

The leaves were welded together by mycelium and a challenge to open. Inside we found insects that looked to be in the larval stage.

Coryceps takaomontana stromaClose up of the ascoma showing the bright yellow tops of the perithecia.

Close up of very mature perithecia.

  Ophiocordyceps dipterigena

An already dried out specimen of Ophiocordyceps dipterigena. Seven teleomorphic stromata and one slender anamorphic conidiphore are growing from a fly (order Diptera, hence the species epithet) laying on its back.
The anamorph is also described as Hymenostilbe dipterigena. It was found in Mashaquipe, Madidi NP.


Ophiocordyceps sp.

At first we thought, finally we found Ophiocordyceps amazonica. However the host insect does not fit the bill. O. amazonica is a parasite on Orthoptera, meaning locusts, grasshoppers & crickets.

The broken larvae with the typical marking of a cockroach (Blattodea sp.) according to Tatiana Sanjuan.


Cordyceps cylindrica


Cordyceps that impressed us with its whitish and very geometrically shaped fruiting body. We were blown away seeing it coming forth from the ground out of its own cavity. Well, it turns out it was not its own cavity but apparently this Cordyceps squatted the home of a Mygalomorph trapdoor spider (Araneae) and is successfully digesting the host.

What looks like fine white threads are the spores ejected out of the asci cells.



Gibellula arachnophila

Gibellula arachnophila

Here a close up of a Gibellula arachnophila, a Cordyceps anamorph we found in the cloud forest near Coroico. Gibellula arachnophila feeds on spiders. A spider is below that white mesh. Gibellula arachnophila produces conidiospores, cloned reproductive cells. Most conidiospores are dispersed already and one can see the conidiphores, the structure on which they grow. Found in Coroico, Yungas, Bolivia.

We got more and more excited during exposing the buried cocoon-like structure of this trap door spider. The lid underside is visible to the right ontop of the outer material of the cocoon. Inside the cocoon is a parasitized spider, that might be in a molting process. Very probably this is Cordyceps cylindrica, which is so far reported from East Asia and the United Kingdom.

Carefully opening the cocoon two days later revealed a Mygalomorph Trapdoor spider that is being digested by a Cordyceps. Spiders are most susceptible to Cordyceps attacks during molting phases. (Check out more spider Cordyceps I found in Columbia). Since we prevented the cocoon from drying out, this Cordyceps sporulated for us.





Akanthomyces novoguineensis 

This could be Akanthomyces novoguineensis, another anamorph that likes to feed on spiders.
Found in Coroico, Yungas, Bolivia.


Cordyceps sphecocephala


Ascomata of Cordyceps sphecocephala. The spots are the ostiole openings of the perithecia. 

Cordyceps sphecocephala is specialized to parasitize wasps, hence its name, "spheco" is derived from attic Greek meaning wasp.




Looking for mushrooms at Wizard Mountain we were accompanied by Fonier and his sons Manuco and Patrick. The boys really got into it!
They found a bunch of Cordyceps, here Patrick looks at a Metacordyceps martialis he found with Larry’s lens, they got to keep in the end.

Note the red-eyed fly resting on the top.

 Metacordyceps martialis

Metacordyceps martialis growing on a larva of a Coleoptera beetle. Metacordyceps martialis clearly has a weakness for the juicy coleopteran larvae that never will get to experience how it feels to transform into a big, well protected rain forest beetle. Coleoptera is largest order in the animal kingdom with more than 350,000 described species. The name is derived from the Greek koleon (κολεον) meaning "sheath" and ptera (πτερα) meaning "wings". Aristotle already called beetles 'koleopteros' (κολεοπτερος) to refer to the front wings modified to protect the membranous hind wings (Coleoptera info from Already in 2012 we found several of these attractive Metacordyceps martialis at Wizard mountain during Mushroaming Bolivia.


 Close-up of the ascoma of Metacordyceps martialis. The fruiting body is still immature and the ascoma with the perithecia is not developed yet. The white top of the stroma is still differentiating. The lower part of the top shows ostioles, future openings through which spores will be released which are produced in the perithecia embedded in the ascoma.

Metacordyceps (Clavacipitaceae) as a genus is still not well established, Kegler et al. (2011) wrote in their paper on Metacordyceps: “Metacordyceps remains one of the most poorly understood”. However, “Anamorph genera Metarhizium and Pochonia were found to be associated only with Metacordyceps and demonstrated to be phylogenetically informative for the clade”.

Ophiocordyceps melolonthae

Ophiocordyceps melolonthae is growing on a coleopteran beetle larva. Found in Coroico, Yungas, Bolivia

Another Ophiocordyceps melolonthae growing also on a coleopteran beetle larva. Found near Mashaquipe, Madidi National Park, Bolivia.

Bright yellow pigmented stroma of Ophiocordyceps melolonthae, the head being clearly distinguished, a clear separation of the ascoma, the fertile tissue with asci cells containing perithecia of the 'head' and lower sterile tissue of the stem.

Same fungus down in the Amazon Rain Forest

Close-up of ascoma and parasitized host, a coleopteran larva.


 Ophiocordyceps nutans

The same specimen of Ophiocordyceps nutans showing top and bottom of a Shield or Stink bug (Pentatomidae, Heteroptera)

Another specimen of Ophiocordyceps nutans. Interestingly one of the stroma is a teleomorph, the other the anamorph. In the past the anamorph would have a different species name than the teleomorph, but a new rule says it needs to be the same name, since it is the same organism, just using a different reproductive path. 

The thicker ascoma in the back is the teleomorph. Within its perithecia, asci cells are located in which spores are sexually produced. In the front the anamorph, the asexual stroma of Hymenostilbe nutans.

Ophiocordyceps curculionium

Ophiocordyceps curculionium is specialized in attacking weevils. It is closely related to Ophiocordyceps australis, which attacks ants.

Ophiocordyceps australis

Ophiocordyceps evansii, closely related to O. australis. We find these ant Cordyceps most frequently. Also tiny, the bright red ascomata are easily spotted when scanning the forest floor and dead trunks hunting for Cordyceps.


Ophiocordyceps evansii on Pachycondyla crassinoda ant.


Ophiocordyceps australis growing out of an ant with three tall immature stromata and a forth smaller immature branching off below a mature, pin-head shaped ascoma.

Close up of mature and immature stromata.

Ophiocordyceps tiputini

Ophiocordyceps tiputini sp. nov. with yellow ascomata and branched blackish stroma on Megaloptera larva. Tatiana Sanjuan provided the name for this unusual Cordyceps we found in Mashaquipe.



Unidentified Cordyceps on colopteran larva

Unknown Cordyceps

Another Cordyceps we found in Mashaquipe's Cordyceps corner



A Cordyceps growing on a Colopteran larva, of which only a part was successfully unearthed.


Colombian Cordyceps Species

Submitted by cordyceps on Sun, 03/10/2013 - 17:13

Searching the oak (Quercus humboldtii) dominated montane cloud forest in Chicaque near Bogota, Colombia, Tatiana Sanjuan (see below) and I found an array of Cordyceps-species.  We were very lucky since there had been only one good rain that announced the end of the the dry season.

A Cordyceps currently classified with Cordyceps caloceroides, a spider parasite. Its fruiting bodies have pushed open a spider's egg sac. This Cordyceps specimen is only about 5 mm tall.

An other Cordyceps caloceroides.


Another Cordyceps caloceroides group Cordyceps growing on an idiopidae spider

 below a close up of the still immature fruiting body.



A Cordyceps very close to Cordyceps variabilis

Note the sterile apex of the stroma that bears a fertile cushion in which perithecioid ascomata are immersed. The host insect should be a fly larva.

Here a link to a paper by Kathy Hodges, Richard Humber & Chris Wozniack (1998) on Cordyceps variabilis.


Isaria anamorphs

Isaria tenuipes (= Paecilomyces tenuipeswhen freshly found. 

 Digging out carefully Isaria tenuipes (=Paecilomyces tenuipesshow the parasitized insects that serve as host. We saw probaly nearly a dozen Isaria during our two day excursion. 

An unidentified Cordyceps anamorph.

 Tatians Sanjuan, a leading expert on neo-tropical Cordyceps, was so kind to take me out in the woods. I had promised to share some of my photography techniques and she delivered Cordyceps objects!
Very interesting was Tatiana's confidence in Cordyceps showing up in the same location year after year.  




Caterpillar fungus Interview in China Daily Dec.17, 2012

Submitted by cordyceps on Sun, 02/17/2013 - 09:23

Below I am posting an interview that was published in China Daily, the English language newspaper published by the government of the People's Republic of China. Over four months passed between interview and publication. Speculations regarding the strange title China Daily chose can be found at the end of this blog.

"Threats stem from lack of statistics, over-harvesting"

China Daily  2012-12-17

First Person | Daniel Winkler

China Daily Editor's note: Daniel Winkler, a German ecologist, has researched caterpillar fungus and its economic effects on China for 15 years. A study he conducted in 2005 with Losang Dradul [= Luorong Zhandui] of the China Tibetology Research Center motivated authorities in the Tibet Autonomous Region to introduce a licensing system for fungus harvesting and to keep track of the yearly output. [Not correctly reported: there were already licenses on county level in TAR and data was also collected, but aftersubmission of Luorong's report the first TAR-wide Cordyceps regulation was passed and a conference convened to improve management.]


Over-harvesting and poor statistical tracking of caterpillar fungus are major challenges for the sustainable management of the medicinal resource.

Many rural Tibetans rely on this fungus for their incomes, and if anything happens to it, they will face big problems.

Collectors should realize old, low-value caterpillar fungus is better off left in the ground to spread spores for the next year. But at the moment, hundreds of thousands of people are going into the mountains to collect as much as they can. They can’t find everything, but not much is left, and if the situation remains unchecked, the resource will be depleted sooner or later.

Authorities should shorten the harvest season and further limit the number of collectors - for example, only two members should come from each household.

If these restrictions are to work, the key is education. Officials need to work with community leaders to raise awareness to protect the resource so they can benefit for many years to come.

I visited Tibetan communities with collection rights in Yushu prefecture, Qinghai province, with representatives from the China branch of the World Wildlife Fund for Nature. I showed images to villagers to explain the fruiting stages of caterpillar fungus and the different market values.

It only took a few minutes to convince them that the mushroom needs spores to reproduce, contrary to local belief that it just grows by itself every year.

Policymakers should regulate the market to put people off old, low-value caterpillar fungus, which shrinks substantially after it's dried. Then collectors will have the incentive to give up collecting it.

The price rose by 900 percent between 1998 and 2008, when it then dropped 20 percent due to the financial crisis. The rise in price over the past four years is not as high as before, but harvests have fluctuated, as abundant production depends on sufficient rain and snowfall.

There are several research institutes in China devoted to genetic studies and artificial cultivation of caterpillar fungus [but these institutes have NOT succeeded in cultivating caterpillar fungus], which is good news for Tibetan collectors who face serious competition and a price collapse.

However, more resources should be used to find out how to manage the collection of a natural product in a sustainable way, rather than learn how to cultivate artificial ones.

Daniel Winkler was talking to Li Yao and Daqiong. [I have never talked to Daqiong]


Daniel Winkler's past publishing notes: 
The sentences in brackets I have added in my blog 
above to correct erroneous statements by Li Yao. 

I never talked to Daqiong, and if he would have been present at the interview in Beijing I am convinced the story would not have had the title they cooked up, since my complain of lack of statistics was aimed at Qinghai Province, the biggest producer of caterpillar fungus as well as the Tibetan areas in Sichuan, Yunnan and Gansu that also lack government efforts to keep track of the most precious product of this region.

Now the title is apparently in juxtaposition to a lengthy article published on the same day in China Daily, to which Daqiong probably contributed substantially. Interestingly the very informative article is full of statistics, never published before. To me the choice of header for my interview in juxtaposition to the TAR caterpillar fungus article seems to try to leave the impression that I was clueless in regard of the statistics kept in TAR. However, in 2008 and 2011 I had published previous years of some of these statistics and my complain regarding lack of statistics was not aimed at TAR, but the other Cordyceps producing areas outside of TAR. However Li Yao did not inform me that China Daily was publishing a second Cordyceps paper on the same day.

Daniel Winkler portrait with Boletus edulis

Ecologist holding a porcini mushroom in 2007.

Daniel Winkler Luorong Zhandui Dawa Dengqen 2005 
Daniel, Luorong Zhangdui, and Dawa from Peking's China Tibet Research Center in Dengqen County, Qamdo Prefecture, TAR, during the Cordyceps field research in 2005. Note the Yartsa gunbu collectors camps on the slopes. (Picture was not in China Daily article)






New Research Papers on Himalayan Caterpillar Fungus Collection

Submitted by cordyceps on Sat, 02/16/2013 - 06:47

Two new papers on Ophiocordyceps sinensis collection in the Himalayas were just recently published, one by C.P. Kuniyal and R.C. Sundriyal on the role of caterpillar fungus in the context of rural livelihood in selected villages in Uttarakhand, the other by U.B. Shrestha & K.S. Bawa on Yartsa gunbu trade harvest and conservation in Nepal's Dolpa region. Both studies offer detailed data on local level shedding light on the situation of the caterpillar fungus industry. Not surprisingly both studies raise the issue of sustainability, an issue looming large after several poor years of harvest. The Dolpa study reports based on over 200 interviews with collectors and traders that 2/3 of the stakeholders are concerned about the sustainability. It offers lots of insight and discusses a whole range of possibilities that could have caused the decline in recorded harvest in the last decade, such as increased collection pressure especially caused by more collectors and increasing value, potential reduction of ghost moth population, climate change etc. Unfortunately there are no answers to what forces are the major factors in harvest reduction, but this a very complex questions and so far there are no studies that would be able to answer this  crucial question. Shresta and Bawa do not offer suggestions how to approach this challenge, whereas the authors of the Uttarakhand study Kuniyal and Sundriyal suggest rotational harvest to diminish negative impact by rotating collection. Though this is no new idea, I have my doubts about feasibility for two reason: firstly, enforcement is very difficult. Keeping collectors off designated areas for 3 out of 4 years seems impossible to me. Secondly, since Yartsa gunbu fruiting is an annual event, host and fungus are dying each year, I am wondering if after three years of fallow, one year of very intense collection might just wipe out the benefits of the fallow. There is still no conclusive empirical research on successful sustainable caterpillar fungus research. In my opinion reducing the continuous collection intensity - be it limiting the collection time to 4 weeks and/or limiting the amount of collectors allowed to enter Yartsa gunbu habitat might be a better match for an organism that infects its hosts each year anew and is distributed in extremely remote areas. However, as Shresta and Bawa point out the build up of functioning local institutions is crucial for creating the capacity of meaningful sustainable management, a process that is in Dolpa underway but far from completed. 

Titles and Abstracts

U.B. Shrestha, K.S. Bawa 2013. Trade, harvest, and conservation of caterpillar fungus (Ophiocordyceps sinensis) in the Himalayas.  Biological Conservation 159 (2013) 514–520.

Abstract: Unsustainable trade in wildlife is regarded as a major driver of biodiversity loss and ecosystem degradation.
Unregulated wildlife trade propels over-exploitation of species, resulting in population declines, and
often in combination with other factors may ultimately extirpate species from their natural habitats.
Concern about the impacts of trade on biodiversity has largely focused on flagship animal species. Here,
we report on the impact of trade on natural populations of the world’s most expensive biological
resource, a unique caterpillar fungus (Ophiocordyceps sinensis). Based on interviews with 203 harvesters
and 28 traders, and focus group discussions in Dolpa, Nepal, we quantify the amount of harvest and trade.
After legalization of trade in Nepal in 2001, trade volume increased persistently, reaching a peak of
2442.4 kg in 2009 and subsequently declining to 1170.8 kg in 2011. The local market price has increased
by up to 2300% over the last 10 years. However, mean annual harvest declined from
260.66 ± 212.21 pieces per person in 2006 to 125.82 ± 96.84 pieces per person in 2010. Our analysis of
harvesters’ perceptions of resource abundance and sustainability shows that virtually all harvesters
(95.1%) believe the availability of the caterpillar fungus in the pastures to be declining, and 67% consider
current harvesting practices to be unsustainable.

Kuniyal, C.P., Sundriyal, R.C. 2013. Conservation salvage of Cordyceps sinensis collection in the Himalayan mountains is neglected.  Ecosystem Services  

Abstract :Traditional agriculture and animal rearing are central in the rural livelihood of Himalayan Mountains.
Economically these activities are inadequate for fulfilling the better livelihood expectation. Therefore rural
people depend on diverse short seasonal activities like collection of medicinal plants, timber trading and
animals poaching etc. for obtaining economic benefits. In past few years, collection of Cordyceps sinensis in
the Himalayan Mountains has been emerged as main short seasonal activity. This practice is more
profitable as compared to the cultivation of key cash crops and some other activities. Because of attractive
economic benefits, nearly 52.08 to 97.98% households of this region are involved in the short seasonal
collection of C. sinensis. Development of C. sinensis in the Himalayan Mountains and economic benefit
earned from its collection is valuable ecosystem service. Uncontrolled collection of C. sinensis will be critical
for its sustainability. Hence rotational pattern for collecting C. sinensis will be useful for its long-term
availability. Because of the shift in short seasonal activities of poor communities, collection of C. sinensis
may be helping in conservation of globally significant medicinal plants (GSMPs), timber yielding trees and
wild animals. However, impacts of this short seasonal activity on the population recovery of GSMPs, timber
trees and wild animals need to be studied at habitat level. Economic benefits earned from short seasonal
collection of C. sinensis and cultivation of key cash crops, suggestion for sustainable collection of C. sinensis,
possible impacts after deviation from this practice and indirect salvage of this short seasonal activity for the
conservation of other resources is discussed in this communication.



Cordycepin: Anti-Inflammatory and Anti-Aging Capacity

Submitted by cordyceps on Fri, 12/28/2012 - 11:18

Recently two interesting research papers on medical propensities of Cordycepin, the most well known of the active ingredients of wild Ophiocordyceps sinensis and also cultivated O.s as well as Cordyceps militaris, were published. The first study presents results of ongoing research at Nottingham University (UK) under the leadership of Dr. Cornelia De Moor. It is entitled: "Inhibition of polyadenylation reduces inflammatory gene induction" and published in RNA. The other paper published in Experimental Gerontology by a mostly Korean team is entitled: "Cordycepin (3′-deoxyadenosine) attenuates age-related oxidative stress and ameliorates antioxidant capacity in rats" and its summary - see below -closes with: "These results suggest that cordycepin is effective for restoring antioxidant status and decreasing lipid peroxidation in aged rats. Aging leads to the gradual loss of pro-oxidant/antioxidant balance and increase oxidative stress. Cordycepin treatment decrease oxidative stress and increase antioxidant status Cordycepin treatment can ameliorate antioxidants during aging and it might attenuate the age-associated disorders".

Now, I do not have the medical back ground to judge the content or the value of these research articles. However, the Nottingham study suggests that Cordycepin has anti-inflammatory capacity that is worth to be investigated further for potential drug development. The Korean study is packed with graphics that leave the impression that negative impact from aging on cellular level has been reduced substantially in rats that have been treated with Cordycepin.

Of course these studies do not address the medical value of natural Yartsa gunbu, the complex of the ghost moth larva taken over by caterpillar fungus - Ophiocordyceps sinensis. However, they clearly indicate that the attention that Yartsa gunbu as a medicinal fungus receives is not made out of thin air.

References with abstracts:

Kondrashov, A., Hedda A. Meijer, Adeline Barthet-Barateig, Hannah N. Parker, Asma Khurshid, Sarah Tessier, Marie Sicard, Alan J. Knox, Linhua Pang, and Cornelia H. De Moor 2012. Inhibition of polyadenylation reduces inflammatory gene induction. RNA 2012. 18: 2236-22502

Cordycepin (39 deoxyadenosine) has long been used in the study of in vitro assembled polyadenylation complexes, because it terminates the poly(A) tail and arrests the cleavage complex. It is derived from caterpillar fungi, which are highly prized in Chinese traditional medicine. Here we show that cordycepin specifically inhibits the induction of inflammatory mRNAs by cytokines in human airway smooth muscle cells without affecting the expression of control mRNAs. Cordycepin treatment results in shorter poly(A) tails, and a reduction in the efficiency of mRNA cleavage and transcription termination is observed, indicating that the effects of cordycepin on 39 processing in cells are similar to those described in in vitro reactions. For the CCL2 and CXCL1 mRNAs, the effects of cordycepin are post-transcriptional, with the mRNA disappearing during or immediately after nuclear export. In contrast, although the recruitment of RNA polymerase II to the IL8 promoter is also unaffected, the levels of nascent transcript are reduced, indicating a defect in transcription elongation. We show that a reporter construct with 39 sequences from a histone gene is unaffected by cordycepin, while CXCL1 sequences confer cordycepin sensitivity to the reporter, demonstrating that polyadenylation is indeed required for the effect of cordycepin on gene expression. In addition, treatment with another polyadenyation inhibitor and knockdown of poly(A) polymerase a also specifically reduced the induction of inflammatory mRNAs. These data demonstrate that there are differences in the 39 processing of inflammatory and housekeeping genes and identify polyadenylation as a novel target for anti-inflammatory drugs.

Thiyagarajan Ramesh, Sung-Kwang Yoo, Sung-Won Kim, Seock-Yeon Hwang, Sang-Hyun Sohn, Il-Woung Kim, Si-Kwan Kim 2012. Cordycepin (3′-deoxyadenosine) attenuates age-related oxidative stress and ameliorates antioxidant capacity in rats. Experimental Gerontology Volume 47, Issue 12, December 2012, p. 979–987

Free radical-induced oxidative damage is considered to be the most important consequence of the aging process. The activities and capacities of antioxidant systems of cells decline with increased age, leading to the gradual loss of pro-oxidant/antioxidant balance and resulting in increased oxidative stress. Our investigation was focused on the effects of cordycepin (3'-deoxyadenosine) on lipid peroxidation and antioxidation in aged rats. Age-associated decline in the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), reduced glutathione (GSH), vitamin C and vitamin E, and elevated levels of malondialdehyde (MDA) were observed in the liver, kidneys, heart and lungs of aged rats, when compared to young rats. Furthermore, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, and creatinine were found to be significantly elevated in aged rats compared to young rats. Aged rats receiving cordycepin treatment shows increased activity of SOD, CAT, GPx, GR and GST, and elevated levels of GSH, and vitamins C and E such that the values of most of these parameters did not differ significantly from those found in young rats. In addition, the levels of MDA, AST, ALT, urea and creatinine became reduced upon administration of cordycepin to aged rats. These results suggest that cordycepin is effective for restoring antioxidant status and decreasing lipid peroxidation in aged rats. Aging leads to the gradual loss of pro-oxidant/antioxidant balance and increase oxidative stress. Cordycepin treatment decrease oxidative stress and increase antioxidant status Cordycepin treatment can ameliorate antioxidants during aging and it might attenuate the age-associated disorders.